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Kyrylova, Oksana, Vladlena Myronenko, and Yuliia Harkavenko. "Electronic newsletter in the system of social communications: prospects for effective use." Вісник Книжкової палати, no. 3 (March 28, 2024): 12–18. http://dx.doi.org/10.36273/2076-9555.2024.3(332).12-18.
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The article substantiates the necessity to expand research methodologies into the electronic newsletter format. It was acknowledged that modern scientific discourse reluctantly chooses the electronic bulletin as an object of research. At the same time, scholars concur with the fact that this format demonstrates potential while being a user-friendly channel of communicative interaction as well as providing an opportunity to create personalised communication and offer exclusive content, etc. The article examines the examples of the most sought-after newsletters such as: editorial newsletters from The New York Times, aggregated newsletters from SmartBrief, Think with Google resource, The Menu newsletter from SparkToro technical startup, Confident Computing's latest technology newsletter from Ask Leo! website and the female-focused Daily Skimm newsletter from theSkimm media company. The specifics, characteristics, and advantages of this form of interaction with the audience are analysed. It is concluded that tailored personalised content that the user receives via e-mail allows the company to effectively communicate, interact with its target audiences, increasing the level of engagement, building trust and upholding reputation. In this case, the indicators of the website opening, clickability and conversion, make it possible to improve the strategy of email distributions, which will ensure better results. The electronic newsletter is a modern, up-to-date format which helps to perform effective multi-functional social communication, provided it contains interesting, high-quality, interactive, scheduled content aimed at the target audience.
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Warren, R. B., H. Sofen, S. Imafuku, J. Szepietowski, A. Blauvelt, L. Spelman, E. Colston, et al. "POS1046 DEUCRAVACITINIB LONG-TERM EFFICACY AND SAFETY IN PLAQUE PSORIASIS: 2-YEAR RESULTS FROM THE PHASE 3 POETYK PSO PROGRAM." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 841.1–841. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2445.
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BackgroundTyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signalling of key cytokines (eg, interleukin [IL]-23 and Type I interferons) involved in the pathogenesis of immune-mediated diseases including plaque psoriasis and psoriatic arthritis (PsA). Deucravacitinib is a novel, oral, selective TYK2 inhibitor that achieves high selectivity by uniquely binding to the regulatory domain of the enzyme, rather than to the more conserved active domain. Deucravacitinib showed superior efficacy compared with placebo at 16 weeks in a Phase 2 trial in patients with PsA.1 The efficacy and tolerability of deucravacitinib in patients with moderate to severe psoriasis were previously demonstrated in 2 pivotal, Phase 3, double-blind trials, POETYK PSO-1 and PSO-2.2ObjectivesTo assess the long-term efficacy and safety of deucravacitinib in patients with psoriasis in a Phase 3, open-label, long-term extension (LTE) trial.MethodsThe 52-week PSO-1 and PSO-2 trials randomised patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients could then enrol in the LTE trial and receive open-label deucravacitinib 6 mg once daily.Results1221 patients enrolled in the LTE trial and received ≥1 dose of deucravacitinib. Demographic and baseline disease characteristics were balanced across treatment groups; mean age at disease onset was 28.6 years, mean disease duration was 18.9 years, and 18.0% of patients had PsA at baseline. Cumulative exposures in person-years from randomisation in PSO-1 or PSO-2 and the LTE trial were 2166.9 and 2482.0 for efficacy and safety analyses, respectively. At enrolment in the LTE trial, PASI 75 and sPGA 0/1 response rates were 65.1% and 50.9%, respectively, and were maintained for up to 2 years after initial randomisation (Week 48 of LTE; PASI 75: 75.7%; sPGA 0/1: 56.4% [as observed]). Exposure-adjusted incidence rates per 100 person-years for adverse events were similar in the controlled period (Weeks 0–52) of PSO-1 and PSO-2 and during the cumulative PSO-1, PSO-2, and LTE trial period (229.2 [controlled period] vs 154.4 [cumulative period]), serious adverse events (5.7 vs 6.1), discontinuations (4.4 vs 2.8), deaths (0.2 vs 0.4), herpes zoster (0.9 vs 0.7), malignancies (1.0 vs 0.9), major adverse cardiovascular events (0.3 vs 0.4), and venous thromboembolism (0.1 vs 0.1).ConclusionDeucravacitinib demonstrated persistent efficacy and consistent safety profiles in patients with psoriasis for up to 2 years after initial randomisation in the POETYK PSO-1, PSO-2, and LTE trials.References[1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).[2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Writing and editorial assistance was provided by Lisa Feder, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, funded by Bristol Myers Squibb.Disclosure of InterestsRichard B. Warren Consultant of: AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, UNION, and Xenoport, Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Janssen, Eli Lilly, Leo Pharma, Novartis, Pfizer, UCB, Howard Sofen Consultant of: Clinical investigator: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma., Shinichi Imafuku Grant/research support from: Grants and personal fees: AbbVie, Eisai, Kyowa Kirin, Janssen, Leo Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi, and Torii Yakuhin; Personal fees: Amgen (Celgene), Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB, Jacek Szepietowski Consultant of: Advisory board member/consultant: AbbVie, Leo Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; Speaker: AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and Sanofi Genzyme; Investigator: AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRX, Janssen-Cilag, Manlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, and Trevi, Andrew Blauvelt Consultant of: Scientific adviser and/or clinical study investigator: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Vibliome, Lynda Spelman Consultant of: Consultant, paid investigator, and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Bristol Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck (MSD), Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma ANZ, Trius, UCB, and Zai Lab, Elizabeth Colston Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Jessica Toms Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Alex Buck Employee of: Contractor (through functional service provider Cytel): Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Alan Menter Consultant of: Advisory board: Abbott Labs, Amgen, Boehringer Ingelheim, Janssen Biotech, Leo Pharma; consultant: Abbott Labs, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: Abbott Labs, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: Abbott Labs, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB
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Armstrong, A., M. Gooderham, R. B. Warren, K. Papp, B. Strober, D. Thaçi, E. Colston, et al. "POS1042 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 (TYK2) INHIBITOR, COMPARED WITH PLACEBO AND APREMILAST IN MODERATE TO SEVERE PLAQUE PSORIASIS: RESULTS FROM THE PHASE 3 POETYK PSO-1 STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 795.1–796. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1002.
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Background:Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates interleukin (IL)-23, IL-12, and interferon (IFN)α/β signaling. Deucravacitinib is a novel, oral, selective inhibitor of TYK2 acting via binding to the TYK2 regulatory domain.1 Phase 2 results showed deucravacitinib was efficacious and well tolerated versus placebo in patients with moderate to severe plaque psoriasis or active psoriatic arthritis.2,3 No herpes zoster infections, opportunistic infections, thromboembolic events, or hematologic or lipid abnormalities characteristic of Janus kinase (JAK) 1−3 inhibitors were reported in the Phase 2 trials.2,3Objectives:To compare the efficacy and safety of deucravacitinib versus placebo and apremilast in plaque psoriasis.Methods:This Phase 3, double-blinded, 52-week study (NCT03624127) randomized patients with moderate to severe plaque psoriasis (BSA ≥10%, PASI ≥12, sPGA ≥3) to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily (2:1:1). Patients receiving placebo were switched to deucravacitinib at Week 16; apremilast-treated patients not achieving PASI 50 at Week 24 were switched to deucravacitinib. Coprimary endpoints were PASI 75 and sPGA 0/1 response versus placebo at Week 16. Key secondary endpoints included superiority versus apremilast, assessed via multiple measures.Results:666 patients were randomized. Demographic and baseline disease characteristics were balanced across groups; mean age was 46.1 years, mean disease duration was 17.3 years, 18.2% of patients had psoriatic arthritis at baseline, and 38.9% had previously used biologic therapy. Mean BSA involvement at baseline was 26.3%, mean PASI was 21.4, and the percentage with severe sPGA (score=4) at baseline was 21.2%. Significantly greater proportions of patients in the deucravacitinib versus placebo and apremilast arms achieved PASI 75 (58.7% vs 12.7% vs 35.1%, respectively; P<0.0001) and sPGA 0/1 (53.6% vs 7.2% vs 32.1%, respectively; P<0.0001) response at Week 16 (Figure 1). Deucravacitinib was also superior to apremilast at Week 24, with 69.0% versus 38.1% of patients achieving PASI 75 and 58.4% versus 31.0% achieving sPGA 0/1 (P<0.0001 for both). In addition, DLQI 0/1 responses at Week 16 were significantly higher with deucravacitinib versus placebo and apremilast, demonstrating improved quality of life (40.7% vs 10.6% vs 28.6%, respectively; Figure 1). During the 16-week, placebo-controlled period, the most common AEs (≥5% in any arm) were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and nausea (Table 1). Frequencies of SAEs and treatment discontinuations due to AEs were low (Table 1).Table 1.Summary of adverse events (AEs) through Week 16Patients, n (%)Deucravacitinibn=332Placebon=165Apremilastn=168Any AEs176 (53.0)70 (42.4)93 (55.4)Severe AEs5 (1.5)7 (4.2)5 (3.0)Serious AEs7 (2.1)9 (5.5)4 (2.4)AEs leading to treatment discontinuation6 (1.8)7 (4.2)10 (6.0)Most common AEs (≥5% in any arm) Nasopharyngitis21 (6.3)7 (4.2)14 (8.3) Upper respiratory tract infection21 (6.3)6 (3.6)3 (1.8) Headache16 (4.8)5 (3.0)17 (10.1) Diarrhea13 (3.9)6 (3.6)17 (10.1) Nausea7 (2.1)4 (2.4)19 (11.3)Conclusion:Deucravacitinib demonstrated superiority versus placebo and apremilast across multiple efficacy endpoints in patients with moderate to severe plaque psoriasis, and was generally well tolerated. Overall, the efficacy and safety profile of deucravacitinib was consistent with that observed in the Phase 2 plaque psoriasis and psoriatic arthritis trials.2,3References:[1]Burke JR et al. Sci Transl Med. 2019;11:1-16.[2]Papp K et al. N Engl J Med. 2018;379:1313-21.[3]Mease PJ et al. Presented at: Annual Scientific Meeting of the American College of Rheumatology; November 5-9, 2020; Virtual meeting.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:April Armstrong Consultant of: Grants and personal fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis; Personal fees from Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, Valeant, Grant/research support from: Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work; Grants and personal fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, Melinda Gooderham Shareholder of: Speakers bureau, consultant, investigator/advisor: AbbVie, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant, Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, Sanofi, Xenoport, UCB, Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Janssen, Eli Lilly, Leo Pharma, Novartis, Pfizer, UCB, Kim Papp Speakers bureau: AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Valeant, Consultant of: Scientific officer/steering committee/advisory board: AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Valeant, Grant/research support from: AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Leo Pharma, MedImmune, Meiji Seika Pharma, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant;Consultant: AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, Merck Sharp & Dohme, Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant; Honoraria: AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Takeda, UCB, Valeant, Bruce Strober Speakers bureau: AbbVie, Janssen, Eli Lilly, Ortho Dermatologics, Consultant of: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, GSK, Janssen, Kyowa Hakko Kirin, Leo Pharma, Medac, Meiji Seika Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB; Scientific Director (consulting fee): Corrona Psoriasis Registry; Investigator: AbbVie, Corrona Psoriasis Registry, Dermavant, Dermira., Diamant Thaçi Paid instructor for: Lectures: AbbVie, Almirall, Amgen, DS-Pharma, Janssen, Leo Pharma, MSD, Novartis, Pfizer, Roche-Posay, Sandoz-Hexal, Sanofi, Target-Solution, UCB; Scientific advisory board: AbbVie, Amgen, Celgene, DS Pharma, Eli Lilly, Galapagos, Janssen-Cilag, Leo Pharma, Morphosis, MSD Novartis, Pfizer, Sandoz, Sanofi, UCB., Consultant of: Consultant: AbbVie, Almirall, Celgene, Dignity, Galapagos, Leo Pharma, Maruho, Mitsubishi, Novartis, Pfizer, Xenoport, Grant/research support from: Research support/principal investigator (clinical trials): AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Chugai, Dermira, DS-Pharma, Eli Lilly, Galderma, GSK, Janssen-Cilag, Leo, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, UCB, Elizabeth Colston Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, John Throup Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sudeep Kundu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Andrew Blauvelt Consultant of: Scientific adviser and/or clinical study investigator for AbbVie, Aligos, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma.
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Warren, R. B., A. Armstrong, M. Gooderham, B. Strober, D. Thaçi, S. Imafuku, H. Sofen, et al. "AB0890 Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 Inhibitor, in Moderate to Severe Plaque Psoriasis: 52-Week Efficacy Results From the Phase 3 POETYK PSO-1 and POETYK PSO-2 Trials." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1570–71. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1377.
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BackgroundTyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signaling of key cytokines (eg, interleukin [IL]-23 and Type I interferons) involved in the pathogenesis of immune-mediated diseases including plaque psoriasis and psoriatic arthritis (PsA). Deucravacitinib is a novel, oral, selective, allosteric inhibitor of TYK2 that achieves high selectivity by uniquely binding to the regulatory domain of the enzyme, rather than to the more conserved active domain. Deucravacitinib showed superior efficacy compared with placebo at 16 weeks in a Phase 2 trial in patients with PsA (NCT03881059). Results from the 16-week, placebo-controlled periods of two 52-week, Phase 3 trials in psoriasis (POETYK PSO-1 and POETYK PSO-2) previously showed that deucravacitinib was significantly more efficacious than placebo and apremilast based on the coprimary endpoints of ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at Week 16.ObjectivesTo evaluate the efficacy of deucravacitinib over 52 weeks in the POETYK PSO-1 and POETYK PSO-2 trials.MethodsPOETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were double-blinded trials that randomised patients with moderate to severe plaque psoriasis (body surface area involvement ≥10%, PASI ≥12, sPGA score ≥3) 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients receiving placebo were switched to deucravacitinib at Week 16 in both trials. Patients randomised to deucravacitinib in PSO-1 received deucravacitinib continuously through Week 52. PSO-2 included a randomised withdrawal phase in which patients originally randomised to deucravacitinib who had achieved PASI 75 response at Week 24 were rerandomised 1:1 to placebo or deucravacitinib, whereas those who did not achieve PASI 75 response at Week 24 continued receiving deucravacitinib. The proportions of patients achieving PASI 75 and sPGA 0/1 responses were evaluated up to Week 52. Secondary efficacy endpoints evaluated over this period included PASI 90, PASI 100, percentage change from baseline in PASI, sPGA 0 (clear), change from baseline in the Psoriasis Symptoms and Signs Diary (PSSD) symptom score, and Dermatology Life Quality Index (DLQI) 0/1 (no impact on patient’s life).ResultsA total of 666 and 1020 patients were randomised in PSO-1 and PSO-2, respectively. Demographic and baseline disease characteristics were balanced across treatment groups; mean age was 46.6 years, mean disease duration was 18.6 years, 18.4% of patients had PsA, and 34.8% had previously used biologic therapy. PASI 75, PASI 90, and PASI 100 responses were maintained from Week 16 to Week 52 in PSO-1 (Figure 1). Additionally, sPGA responses were maintained during this period (sPGA 0/1: 53.6% to 52.7%; sPGA 0: 17.5% to 23.5%, respectively). Patients who switched from placebo to deucravacitinib at Week 16 demonstrated PASI 75 and sPGA 0/1 responses at Week 52 (68.3% and 53.8%, respectively) comparable to those observed in patients who received continuous deucravacitinib treatment from Day 1 (65.1% and 52.7%, respectively). In PSO-2, among deucravacitinib-treated patients who achieved PASI 75 at Week 24 and were rerandomised to continue treatment, responses were maintained at Week 52 in the majority of patients (PASI 75, 80.4% [119/148]; sPGA 0/1, 70.3% [83/118]). Results for percentage change from baseline in PASI, change from baseline in the PSSD symptom score, and DLQI 0/1 were consistent with those reported for PASI and sPGA responses.ConclusionResults from the Phase 3 POETYK PSO-1 and PSO-2 trials demonstrated that deucravacitinib was efficacious through 52 weeks in patients with moderate to severe plaque psoriasis. Clinical responses were maintained in patients who received continuous deucravacitinib treatment and were improved in patients who switched from placebo at Week 16 to deucravacitinib treatment.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsRichard B. Warren Consultant of: Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, Biogen, and UNION., Grant/research support from: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB;, April Armstrong Grant/research support from: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work., Melinda Gooderham Consultant of: Advisory board, principal investigator, and lecture fees: Arcutis, Galderma, Leo Pharma, Pfizer, and Regeneron; Principal investigator and consulting fees: Akros Pharma and Kyowa Kirin; Advisory board, principal investigator, lecture fees, and consulting fees: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Sanofi Genzyme, and Valeant; Principal investigator: Aslan, Bristol Myers Squibb, Dermavant, Dermira, GlaxoSmithKline, MedImmune, Merck, Roche Laboratories, and UCB., Bruce Strober Consultant of: Consultant (honoraria): AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, Equillium, Janssen, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, GlaxoSmithKline, Ortho Dermatologics, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, Ventyxbio, and vTv Therapeutics; Speaker: AbbVie, Eli Lilly, Janssen, and Sanofi Genzyme; Co-Scientific Director (consulting fee): CorEvitas’ Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas’ Psoriasis Registry, Dermavant, Dermira, and Novartis., Diamant Thaçi Speakers bureau: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB., Shinichi Imafuku Grant/research support from: Grants and personal fees: AbbVie, Eisai, Kyowa Kirin, Taiho, Maruho, Tanabe Mitsubishi, Leo Pharma, Janssen, Sun Pharma, Torii, and Yakuhin; Personal fees: Amgen, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB., Howard Sofen Consultant of: Clinical Investigator: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma., Lynda Spelman Consultant of: Consultant, paid investigator, and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck, Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma, Trius, UCB, and Zai Lab., Neil J Korman Speakers bureau: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB; Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi Genzyme., Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Grant/research support from: Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech., Min Zheng Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly China, Leo Pharma China, Novartis China, Pfizer, Sanofi China, and Xian-Janssen., Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly China, Leo Pharma China, Novartis China, Pfizer, Sanofi China, and Xian-Janssen., Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly China, Leo Pharma China, Novartis China, Pfizer, Sanofi China, and Xian-Janssen., Elizabeth Colston Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, John Throup Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sudeep Kundu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Renata Kisa Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Employees and shareholders: Bristol Myers Squibb, Employee of: Employees and shareholders: Bristol Myers Squibb, Andrew Blauvelt Consultant of: Scientific advisor and/or clinical study investigator: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Vibliome.
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Taylor, P. C., A. G. Bushmakin, J. C. Cappelleri, P. Young, R. Germino, J. F. Merola, and G. Yosipovitch. "AB0837 ITCH AS THE MAJOR MEDIATOR OF THE EFFECT OF TOFACITINIB ON HEALTH-RELATED QUALITY OF LIFE IN PsA: A MEDIATION ANALYSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1723.1–1724. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1808.
Full textAbstract:
Background:PsA is a chronic, systemic inflammatory disease with signs and symptoms across multiple domains, including cutaneous manifestations, which can impact health-related quality of life (HQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. In two Phase 3 randomised studies, patients (pts) with active PsA treated with tofacitinib experienced greater improvements in various dermatologic endpoints, compared with placebo. As pruritus is a bothersome symptom of skin disease in pts with PsA, we sought to determine how tofacitinib affects HQoL via clinical improvements in skin symptoms including itch.Objectives:To determine the relationships between tofacitinib treatment, dermatologic symptoms and pt-reported HQoL related to skin disease in PsA.Methods:Analyses used data (mean scores from Months 1 and 3) from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily or placebo; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response (IR) to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Mediation modelling, a statistical method used to assess mechanisms underlying observed relationships between different variables via other explanatory variables (mediators), was applied. The mediation model included: treatment, as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); HQoL, measured by Dermatology Life Quality Index (DLQI), as the dependent (outcome) variable; and two mediators, pt-reported Itch Severity Index (ISI) and Physician’s Global Assessment of Psoriasis (PGA-PsO) (a latent variable represented by erythema, induration and scaling). The initial model designated the treatment effect on DLQI mediated via ISI and PGA-PsO as an indirect effect, and treatment effects not attributable to ISI or PGA-PsO as a direct effect (Figure 1).Results:Data were collected from 468 pts, pooled from both studies. In the initial model (pooled data), the effect of tofacitinib treatment on DLQI was largely mediated by itch (measured by ISI) and PGA-PsO (indirect effect) (p<0.0001); the effect of treatment attributable to factors other than ISI and PGA-PsO (direct effect) was not statistically significant (p=0.66). Results were consistent for pooled and individual study data. Because the direct effect was small and not statistically significant, the model was re-specified to exclude the direct effect of tofacitinib treatment on DLQI. In the revised model (pooled data), 17.7% of the indirect effect was attributable to PGA-PsO (p=0.0006) and 82.3% was attributable to itch (assessed by ISI) (p<0.0001) (Figure 2). Analyses of individual studies using the revised model gave results generally consistent with pooled data.Conclusion:Dermatology-focused mediation modelling showed that a majority of the effect (~80%) of tofacitinib treatment on DLQI is mediated by improvements in itch, with ~20% mediated via improvements in PGA-PsO.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Gil Yosipovitch Grant/research support from: Galderma, Kiniksa, Leo, Menlo, Novartis, Pfizer, Sanofi Regeneron, Consultant of: Eli Lilly, Galderma, Kiniksa, Leo, Menlo Therapeutics, Novartis, Pfizer Inc, Sanofi Regeneron, Trevi, Sienna
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Fleischmann, R. M., D. Thaçi, M. Gooderham, B. Strober, N. J. Korman, S. Banerjee, T. Lehman, et al. "POS1040 SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR: AS ASSESSED BY LABORATORY PARAMETERS – RESULTS FROM A PHASE 2 TRIAL IN PSORIATIC ARTHRITIS AND 2 PHASE 3 TRIALS IN PSORIASIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 835.2–836. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1862.
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BackgroundDeucravacitinib (DEUC) is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action distinct from Janus kinase (JAK) 1/2/3 inhibitors. DEUC mediates signalling of key cytokines in psoriatic arthritis (PsA) and psoriasis (PsO). DEUC was well tolerated and efficacious vs placebo (PBO) in a Phase 2 trial in patients (pts) with PsA,1 and vs PBO or apremilast in 2 Phase 3 PsO trials.2ObjectivesTo assess the effects of DEUC on multiple laboratory parameters through the first 16 weeks of treatment (PBO-controlled) in these trials.MethodsThe Phase 2 double-blind PsA trial randomised pts (n=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. The Phase 3 double-blind PsO trials, POETYK PSO-1 and POETYK PSO-2, randomised pts (n=666 and 1020, respectively) 1:2:1 to PBO, DEUC 6 mg QD, or apremilast 30 mg twice daily. Changes from baseline in haematologic (neutrophils, lymphocytes, platelets, haemoglobin) and chemistry (cholesterol, triglycerides, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and creatine phosphokinase [CPK]) parameters were evaluated. Shifts in Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) severity grade ≥3 of laboratory abnormalities were assessed.ResultsIn the PsA trial, 65% of pts were on concomitant conventional synthetic DMARDs (csDMARDs) and 54.7% of pts were on methotrexate. The vast majority of pts continued to have laboratory parameters within normal range throughout the 3 trials in PsO and PsA. No clinically meaningful changes from baseline were observed in laboratory parameters in pts treated with DEUC, PBO, or apremilast. Rates of CTCAE grade 3 and 4 were rare (≤1 pt) and similar across DEUC-, PBO-, and apremilast-treated pts for the following parameters: lymphocytes, neutrophils, platelets, haemoglobin, AST, ALT, and cholesterol (Table 1). Shifts to CTCAE grades ≥3 in triglycerides and CPK were infrequent and generally comparable across treatment arms.Table 1.Maximal shifts to Grades ≥3 in laboratory parameters, Weeks 0-16PsA Phase 2PsO Phase 3aCTCAE TermGradePlacebo (n=66)n (%)DEUC 6 mg QD (n=70)n (%)DEUC 12 mg QD (n=67)n (%)Placebo (n=419)n (%)DEUC 6 mg QD (n=842)n (%)Apremilast 30 mg BID (n=422)n (%)BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16Lymphocyte count decreased340000001 (1.4)00000001 (0.2)0001 (0.1)00000Neutrophil count decreased34000000000000001 (0.2)01 (0.1) 01 (0.1)00000Platelet count decreased34000000000000000000000000Anaemia340N/A0N/A0N/A0N/A0N/A0 N/A0N/A0N/A0N/A0 N/A0N/A1 (0.2) N/AAlanine aminotransferase increased34000 000000 0000 0000000000 0Aspartate aminotransferase increased34000000000 01 (1.6)0000 00 01 (0.1)0001 (0.2) 0CPK increased34001 (1.5) 0000 00001 (1.6)1 (0.2) 03 (0.7) 1 (0.2)1 (0.1) 05 (0.6) 6 (0.7)1 (0.2)02 (0.5) 1 (0.2)Cholesterol high3400000000000 00 00 00 00 00000Hypertriglyceridemia34000 01 (1.4) 1 (1.4)2 (2.9) 1 (1.4)1 (1.6) 04 (6.0) 02 (0.5) 1 (0.2)6 (1.5) 04 (0.5)1 (0.1)12 (1.5)2 (0.2)3 (0.7) 08 (2.0) 0aPOETYK PSO-1 and PSO-2 pooled data.BID, twice daily; BL, baseline; CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; DEUC, deucravacitinib; N/A, not applicable because there is no haemoglobin value for CTCAE Grade 4 (life-threatening consequences; urgent intervention indicated); PsA, psoriatic arthritis; PsO, psoriasis; QD, once daily; Wk, week.ConclusionDEUC treatment did not result in clinically meaningful laboratory changes, abnormalities often seen with JAK 1/2/3 inhibition, through 16 weeks of treatment in a Phase 2 trial in PsA, despite two-thirds of pts being on concomitant csDMARDs, and in 2 large Phase 3 trials in PsO.References[1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).[2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsRoy M. Fleischmann Consultant of: Abbvie, Acea, Akros, Amgen, Bristol Myers Squibb, Celtrion, Eli Lilly & Co., Galvani, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi Aventis, Taiho, and UCB., Grant/research support from: AbbVie, Acea, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly & Co., Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Pfizer, Roche/Genentech, Samumed, Sanofi Aventis, and UCB, Diamant Thaçi Consultant of: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS-Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB., Melinda Gooderham Consultant of: Investigator, speaker, advisory board member or consultant for: AbbVie, Akros, Amgen, Anaptys Bio, Arcutis, Aslan, Bausch, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, SUN Pharma, and UCB., Bruce Strober Consultant of: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Equillium, Janssen, Leo Pharma, Eli Lilly, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics, Regeneron, Sanofi-Genzyme, and Ventyxbio; Speaker: AbbVie, Janssen, Lilly, and Sanofi-Genzyme; Scientific co-director (consulting fee): CorEvitas Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Eli Lilly/Dermira, and Novartis., Neil J Korman Consultant of: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB, Grant/research support from: Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech. Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi-Genzyme., Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Employees and shareholders of Bristol Myers Squibb, Employee of: Employees and shareholders of Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Antoine Sreih Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Akimichi Morita Consultant of: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Grant/research support from: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Philip J Mease Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB;
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Cooper, Martin. "From Baking to Business Computing." ITNOW 62, no. 2 (May 8, 2020): 30–31. http://dx.doi.org/10.1093/itnow/bwaa042.
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Egeberg, A., N. Lippert Rosenoe, D. Aagaard, E. Lørup, L. Nymand, L. E. Kristensen, J. Thyssen, et al. "POS0076 DRUG SURVIVAL OF BIOLOGICS AND NOVEL IMMUNOMODULATORS FOR RHEUMATOID ARTHRITIS, AXIAL SPONDYLOARTHRITIS, PSORIATIC ARTHRITIS, AND PSORIASIS - A NATIONWIDE COHORT STUDY FROM THE DANBIO AND DERMBIO REGISTRIES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 256–57. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1054.
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BackgroundDrug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis [1-4].ObjectivesThe objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis.MethodsWe performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy.ResultsThe study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a generally higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis drug survival was generally highest for guselkumab.Figure 1.ConclusionDiffering treatment responses to drugs with various types of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history.References[1]Egeberg A, Ottosen MB, Gniadecki R, et al. Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol 2018; 178(2): 509-19.[2]Gron KL, Glintborg B, Norgaard M, et al. Comparative Effectiveness of Certolizumab Pegol, Abatacept, and Biosimilar Infliximab in Patients With Rheumatoid Arthritis Treated in Routine Care: Observational Data From the Danish DANBIO Registry Emulating a Randomized Trial. Arthritis Rheumatol 2019; 71(12): 1997-2004.[3]Lindstrom U, Glintborg B, Di Giuseppe D, et al. Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis. Rheumatology 2020.[4]Glintborg B, Lindstrom U, Di Giuseppe D, et al. One-year treatment outcomes of secukinumab versus tumor necrosis factor inhibitors in Spondyloarthritis. Arthritis Care Res (Hoboken) 2020.AcknowledgementsWe acknowledge the substantial contribution of the academic hospitals and private clinics and their physicians that report data to DANBIO and DERMBIO.Disclosure of InterestsAlexander Egeberg Speakers bureau: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals, Paid instructor for: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals, Consultant of: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals, Grant/research support from: Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, Nana Lippert Rosenoe: None declared, David Aagaard: None declared, Erik Lørup: None declared, Lea Nymand: None declared, Lars Erik Kristensen Speakers bureau: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Paid instructor for: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Consultant of: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Grant/research support from: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Jacob Thyssen Speakers bureau: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Paid instructor for: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Consultant of: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Grant/research support from: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Simon F. Thomsen Speakers bureau: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., Paid instructor for: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., Consultant of: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., Grant/research support from: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., René Lindholm Cordtz: None declared, Nikolai Loft Speakers bureau: speaker for Eli Lilly and Janssen Cilag., Lone Skov Speakers bureau: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Paid instructor for: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Consultant of: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Grant/research support from: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Lars Erik Bryld: None declared, Mads Rasmussen Speakers bureau: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Paid instructor for: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Consultant of: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Grant/research support from: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Pil Højgaard: None declared, Salome Kristensen: None declared, Lene Dreyer Speakers bureau: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma., Paid instructor for: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma., Consultant of: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma., Grant/research support from: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma.
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Cunningham, Joseph J. "Forgotten Pioneer: Leo Daft and the Excelsior Power Company [History]." IEEE Power and Energy Magazine 16, no. 4 (July 2018): 108–20. http://dx.doi.org/10.1109/mpe.2018.2819038.
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Mohanty, Susmita. "Could future COP talks help to de-junk near-earth space?" Soundings 78, no. 78 (August 1, 2021): 81–85. http://dx.doi.org/10.3898/soun.78.05.2021.
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Space debris has reached alarming proportions and is growing at a frightening pace, because of the expanding number of satellites circulating in Low Earth Orbit (LEO), designed to increase global Internet coverage and provide earth observation data. LEO satellites are now being launched in mega-constellations, including by Elon Musk's company SpaceX. It is time to completely overhaul the 1967 Outer Space Treaty, which was not designed to deal with current problems. The COP forum should therefore include the near-earth environment within its concept of the earth's climate, enabling the UN to acknowledge, as a collective, the growing menace of human-made debris in near-earth space, and, in partnership with the UN-Outer Space Affairs Office (UN-OOSA), call for a new declaration on LEO.
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Lebwohl, M., A. Deodhar, A. Blauvelt, S. Schwartzman, M. Feely, A. Kronbergs, N. Eberhart, et al. "AB1097 MALIGNANCIES WITH LONG-TERM USE OF IXEKIZUMAB IN ADULTS WITH PSORIASIS, PSORIATIC ARTHRITIS, OR AXIAL SPONDYLOARTHRITIS: A POST-HOC ANALYSIS OF DATA FROM 25 RANDOMIZED CLINICAL TRIALS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1773–74. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1264.
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BackgroundThis integrated analysis examines long-term incidence rates (IRs) of malignancies in adults with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) who received ≥1 dose of ixekizumab (IXE) up to 5 years (PsO) or 3 years (PsA, axSpA) in clinical trials.Objectives:MethodsIRs of malignancies were assessed across 25 randomized IXE clinical trials (17 PsO, 4 PsA, 4 axSpA). Malignancy rates were analyzed for pooled studies by years of therapy, through March 2022. Exposure-adjusted IRs per 100 patient-years (PY) are reported.Results6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA, with a cumulative IXE exposure of 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA were included in this analysis. The IRs of malignancies at 1-year intervals up to 5 years for patients with PsO, and up to 3 years for patients with PsA and axSpA, remained low (≤1.2/100 PY) and constant. Malignancies occurred in 141/6892 patients with PsO (IR=0.8), 15/1410 patients with PsA (IR=0.7), and 9/932 patients with axSpA (IR=0.4). Of these cases, non-melanoma skin cancer (NMSC) was reported among 55 patients with PsO (IR=0.3) and 9 patients with PsA (IR=0.4). No incidences of NMSC were reported among patients with axSpA.ConclusionIRs of treatment-emergent malignancies were low and stable among adult patients with PsO, PsA or axSpA receiving IXE treatment in clinical trials over the time periods examined.Figure 1.Exposure-adjusted incidence rates (IR) of malignancies across indications by yearly intervals. Data points on the graph are the IR (95% CI)/100 patient-years (PY) at successive year intervals from year 0-5 (PsO), 0-3 (PsA and axSpA).CI = Confidence interval.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMark Lebwohl Consultant of: Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma, Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy’s Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Corrona), Grant/research support from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, UCB Pharma, Aurinia, Moonlake, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Glaxo Smith & Kline, Janssen,Novartis, Pfizer, UCB, Andrew Blauvelt Speakers bureau: AbbVie, UCB, Consultant of: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, EcoR1, Vibliome, Grant/research support from: AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma Investigator (payments made to my company), Sergio Schwartzman Speakers bureau: AbbVie, Janssen, Lilly, Pfizer, Novartis, UCB, Consultant of: AbbVie, Janssen, Eli Lilly and Company, Pfizer, Novartis, UCB, Myriad, Regeneron, Sanofi, Stelexis, Jubilant, Teijin, National Psoriasis Foundation Medical Boar, Grant/research support from: Lilly, Meghan Feely Shareholder of: Eli Lilly and Company, Speakers bureau: Mount Sinai, Consultant of: Mount Sinai Hospital, NY, Eli Lilly and Company, Aerolase, Castle Biosciences, Galderma Aesthetics, Revian, Sonoma Pharmaceuticals, Suneva Medical, and Sun Pharmaceutical Industries, AAD Investment Committee, AAD Media Expert Team, AEI Leadership Network, Leonine Forum, WDS Committees: Practice Advisory, Finance and Investment, Fundraising and Philanthropic Activities, Prevention Medical Review Board, ASDS Social Media Ambassador, Grant/research support from: Eli Lilly and Company, Mount Sinai, MC Medical Group, The Dermatology and Laser Group, Windsor Dermatology Employment, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Nadia Eberhart Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Danting Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Elsa Inman Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Thorsten Holzkaemper Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Proton Rahman Speakers bureau: AbbVie, Amgen, Celgene, Pfizer, Janssen, Novartis, and Eli Lilly, Consultant of: AbbVie, Amgen, Celgene, Pfizer, Janssen, Novartis, and Eli Lilly, Helena Marzo-Ortega Speakers bureau: Abbvie, Biogen, Eli-Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, UCB, Grant/research support from: Janssen, Novartis, UCB, Kim Papp Speakers bureau: AbbVie, Amgen, Bausch Health/Valeant, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Merck, Novartis, Pfizer, Sanofi, Consultant of: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv Therapeutics, Xencor, Grant/research support from: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv Therapeutics, Xencor, Joseph F. Merola Speakers bureau: J. F. Merola is a consultant for Amgen, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma., Consultant of: J. F. Merola is a consultant for Amgen, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma., Alice B Gottlieb Shareholder of: Xbiotech (stock options for an RA project), Consultant of: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech, Grant/research support from: AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma.
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Yusof, N. S. B., S. M. Sapuan, M. T. H. Sultan, and M. Jawaid. "Life cycle analysis of hybrid oil palm/glass fibre-reinforced polyurethane composites for automotive crash box." Journal of Mechanical Engineering and Sciences 14, no. 3 (September 30, 2020): 7132–40. http://dx.doi.org/10.15282/jmes.14.3.2020.14.0559.
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Currently, the world is getting more poisonous due to the toxic contaminated and wastewater release from the industries activities. The designers should analyse the effect to the environmental and human health, prior starting any manufacturing and fabricating process. This technique able to optimize the company profit and reduced unnecessary cost by predict any consequences and do correction step before the problem emerge for every action taken. Therefore, this paper aim to provide the evidence that the selection of material and manufacturing process used to fabricate ACB has minimum impact on the environment and human health. A few methods can be used to calculate the environmental damage assessment such as network, compare and uncertainty analysis. In this study, analyse calculation method selected to predict the environmental impact. The results for the damage to human health analysis only contribute 0.0125 DALY, analysis results for the hazardous elements such as methane, trichlorofluoromethane and Chlorofluorocarbons produced during the fabrication process only 1.32 x 10-9 DALY. Besides, the major damage elements to ecosystem quality results only contribute 1.97 x 10-4 species.yr. Therefore, the remarkable results show that the process and material selection to fabricate ACB are very low which was below than 0.1 DALY. Moreover, damage assessment for the terrestrial ecotoxicity of pulforming process using oil palm natural/glass fibre reinforced polyurethane composite only contributed 1.13 × 10−10 (species.year). Consequently, the process could not damage the human health and indicates that the process is environmentally friendly and safe for the ecosystem.
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O'Mahony, Brian, Johnny Mahlangu, Kathelijne Peerlinck, Jiaan-Der Wang, Gillian Lowe, Chee Wee Tan, Adam Giermasz, et al. "Health-Related Quality of Life Following Valoctocogene Roxaparvovec Gene Therapy for Severe Hemophilia A in the Phase 3 Trial GENEr8-1." Blood 138, Supplement 1 (November 5, 2021): 4916. http://dx.doi.org/10.1182/blood-2021-146021.
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Abstract Introduction. Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL) through joint pain and disability, treatment burden, and effects on mental and emotional health; chronic pain and mental health are core outcomes for hemophilia gene therapy trials (Iorio, et al. Haemophilia 2018;24[4]:e167-72). In the phase 3 trial GENEr8-1 (NCT03370913), men with severe HA who received valoctocogene roxaparvovec (AAV5-hFVIII-SQ) gene therapy experienced a significant increase in endogenous FVIII activity that resulted in reduced bleeding events and FVIII utilization from baseline through 52 weeks (Ozelo, et al. Res Pract Thromb Haemost 2021;5). Here, we analyzed the impact of valoctocogene roxaparvovec on HRQOL. Methods. Men ≥18 years of age with FVIII ≤1 IU/dL previously receiving standard-of-care FVIII prophylaxis and without history of FVIII inhibitors received one 6x10 13 vg/kg valoctocogene roxaparvovec infusion. This analysis included HIV-negative participants who completed the weeks 49-52 visit. Participants completed QOL questionnaires at baseline and weeks 4, 12, 26, and 52 post-gene therapy infusion. Change from baseline was assessed with a two-sided t-test without multiplicity control. Missing data were not imputed. Measures included the hemophilia-specific Haemo-QOL-A questionnaire, which consists of 6 domain scores (Physical Functioning, Role Functioning, Consequences of Bleeding, Worry, Emotional Impact, Treatment Concern) and Total Score ranging from 0-100 (Rentz, et al. Haemophilia 2008;14[5]:1023-34); and the EQ-5D-5L, a general measure of HRQOL that assesses functional dimensions (Mobility, Self-Care, Usual Activities) as well as Pain/Discomfort and Anxiety/Depression (Herdman, et al. Qual Life Res 2011;20[10]:1727-36). EQ-5D-5L results are reported as visual analog scale (VAS; range, 0-100) and Utility Index Score (range, 0-1), which is calculated from population norms (Janssen, et al. Qual Life Res 2013;22[7]:171-27). Higher scores indicate better HRQOL. The anchor-based clinically important differences (CID) used for the Haemo-QOL-A were 5.5 for Total Score and 6 for domain scores (Quinn, et al. Abstract, Hemophilia Federation of America Virtual Conference, Aug 2020). For the EQ-5D-5L Index, 0.03 was considered a CID (Kaplan. COPD 2005;2[1]:91-7). However, use of general population norms, together with the presence of a disability paradox in hemophilia, causes the EQ-5D-5L to underestimate the negative impact of hemophilia on HRQOL (O'Hara, et al. Haemophilia 2021;27[2]:245-52), likely leading to underestimation of changes in HRQOL. Results. This analysis included 132 participants. At baseline, mean ± standard deviation (SD) Haemo-QOL-A Total Score was 75.7 ± 16.7 (n = 130); at weeks 26 and 52, mean change from baseline in Total Score demonstrated improvement (P <0.0001) at or above the CID threshold (Table). Improvement in Total Score was noted as early as 4 weeks (change from baseline, 3.0 ± 8.5; P = 0.0001) and by week 12 had reached the CID (5.5 ± 8.4; P <0.0001). Domain scores for Physical Function, Role Functioning, and Consequences of Bleeding also improved from baseline (P <0.0001), exceeding the CID at weeks 26 and 52 (Table). Treatment Concern demonstrated improvement from baseline (P <0.001) at weeks 26 and 52, exceeding the CID at week 52. Improvements below the CID were noted for Worry at weeks 26 and 52 (P <0.01) and Emotional Impact at week 52 (P <0.05; Table). At baseline, EQ-5D-5L VAS mean ± SD was 80.1 ± 15.3 (n = 131), which increased by 2.5 ± 13.7 (n = 129) at week 26 and 4.5 ± 13.3 (n = 129) at week 52. Mean ± SD EQ-5D-5L Index Score at baseline was 0.78 ± 0.17 (n = 131); mean ± SD changes from baseline at both week 26 (0.04 ± 0.14 [n = 128]) and 52 (0.04 ± 0.16 [n = 129]) demonstrated improvement (P ≤0.002), exceeding the CID of 0.03. Conclusions. These data demonstrate improvement in core outcomes of mental health (EQ-5D-5L Anxiety/Depression, Haemo-QOL-A Consequences of Bleeding) and pain and discomfort (EQ-5D-5L Pain/Discomfort, Haemo-QOL-A Physical Functioning) as well as ability to perform activities of daily living (EQ-5D-5L Self-Care and Mobility, Haemo-QOL-A Physical Functioning and Role Functioning) for participants with HA following treatment with valoctocogene roxaparvovec compared with their values on standard-of-care FVIII prophylaxis. Figure 1 Figure 1. Disclosures O'Mahony: Freeline: Consultancy; Uniqure: Speakers Bureau; BioMarin Pharmaceutical Inc.: Consultancy. Mahlangu: Baxalta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Catalyst Biosciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biomarin: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Univeristy of the Witwatersrand: Current Employment; Spark: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Unique: Research Funding; Sanofi: Research Funding, Speakers Bureau; Takeda: Speakers Bureau; WFH: Speakers Bureau; ISTH: Speakers Bureau; Springer: Speakers Bureau. Peerlinck: SOBI: Consultancy, Research Funding; Octapharma: Consultancy; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy; Roche: Other: Clinical trial investigator, Research Funding; CSL Behring: Research Funding; Uniqure: Other: Clinical trial investigator; BIoMarin: Other: Clinical trial investigator. Lowe: Biomarin: Research Funding; Novartis: Honoraria; Sobi: Honoraria; Leo: Honoraria; Alexion: Honoraria; Takeda: Honoraria; NovoNordisk: Honoraria. Giermasz: Bayer: Consultancy; ATHN: Consultancy; NovoNordisk: Consultancy; UniQure: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Bioverativ/Sanofi: Consultancy, Research Funding, Speakers Bureau; Sangamo Therapeutics,: Research Funding; Pfizer: Consultancy; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau; BioMarin: Consultancy, Research Funding. Cockrell: Takeda: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; Sanofi: Consultancy; BioMarin: Consultancy; Novo Nordisk: Consultancy; Genentech: Consultancy, Speakers Bureau. Pepperell: Pfizer: Other: Travel support. Chambost: Bayer: Consultancy; BioMarin: Consultancy, Other: Clinical trial investigator; travel support, Speakers Bureau; Roche: Consultancy, Other: Clinical trial investigator; travel support, Speakers Bureau; Sobi: Consultancy, Other: Clinical trial investigator; travel support, Speakers Bureau; Bioverativ: Other: Clinical trial investigator; CSL Behring: Other: Clinical trial investigator; travel support; LFB: Other: Clinical trial investigator; Octapharma: Other: Clinical trial investigator; travel support; Pfizer: Other: clinical trial investigator, Speakers Bureau. Majerus: BioMarin Pharmaceutical Inc.: Consultancy, Other: Clinical trial investigator, Travel support. Skinner: Bayer: Consultancy; BioMarin: Consultancy, Research Funding; Pfizer (DMC): Consultancy; Roche/Genentech: Consultancy, Research Funding; Sanofi: Consultancy; Spark (DMC): Consultancy; Takeda: Consultancy, Research Funding; Freeline: Research Funding; uniQure: Research Funding. Klamroth: Bayer: Consultancy, Other: Clinical trial investigator, Travel support, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Other: Clinical trial investigator, Travel support, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Other: Clinical trial investigator, Travel support, Research Funding, Speakers Bureau; Pfizer: Consultancy, Other: Clinical trial investigator, Travel support, Research Funding, Speakers Bureau; Shire (a Takeda company): Consultancy, Other: Clinical trial investigator, Travel support, Research Funding, Speakers Bureau; BioMarin: Consultancy, Other: Clinical trial investigator, Travel support, Speakers Bureau; Biotest: Consultancy, Other: Travel support, Speakers Bureau; Roche/Cugai: Consultancy, Other: Clinical trial investigator, Travel support, Speakers Bureau; Octapharma: Consultancy, Other: Clinical trial investigator, Travel support, Speakers Bureau; Sanofi: Consultancy, Other: Clinical trial investigator, Travel support, Speakers Bureau; Sobi: Consultancy, Other, Speakers Bureau; Uniqure: Consultancy, Other; LEO: Other, Research Funding, Speakers Bureau; Daiichi Sankyo: Other, Speakers Bureau; Grifols: Speakers Bureau. Quinn: BioMarin Pharmaceutical: Current Employment, Current equity holder in publicly-traded company. Yu: BioMarin Pharmaceutical: Current Employment, Current equity holder in publicly-traded company. Wong: BioMarin Pharmaceutical Inc.: Current Employment, Current equity holder in publicly-traded company. Lawal: BioMarin Pharmaceutical Inc.: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Robinson: BioMarin Pharmaceutical Inc.: Current Employment, Current equity holder in publicly-traded company. Kim: BioMarin Pharmaceutical Inc.: Current Employment, Current equity holder in publicly-traded company.
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Lebwohl, M., A. Deodhar, S. Schwartzman, C. Salvarani, M. Feely, D. Zhu, P. Rahman, et al. "AB1105 LONG-TERM SAFETY OF IXEKIZUMAB TREATMENT IN ADULT PATIENTS WITH PSORIASIS, PSORIATIC ARTHRITIS, OR AXIAL SPONDYLOARTHRITIS: A POST-HOC ANALYSIS OF END-OF-STUDY PROGRAM DATA RELATING TO MAJOR ADVERSE CARDIOVASCULAR EVENTS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1780–81. http://dx.doi.org/10.1136/annrheumdis-2023-eular.3412.
Full textAbstract:
Background:ObjectivesThe objective of this study is to report long-term, end-of-study-program safety outcomes, relating to major adverse cardiovascular events (MACE), in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA) who received ≥1 dose of Ixekizumab (IXE) over 5 years (PsO) or 3 years (PsA, axSpA).MethodsThe incidence of MACE was assessed across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA) examining long-term safety of IXE. MACE rates were analyzed for pooled studies by years of therapy, through March 2022. Exposure-adjusted incidence rates (IRs) per 100 patient-years, at successive year intervals are reported.ResultsThe incidence of MACE was low among patients with PsO (IR=0.5), PsA (IR=0.5), and axSpA (IR=0.3). In the PsO cohort, of the 103 reported MACE cases, 20 were fatal (19.4%), 57 recovered (55.3%), and 17 recovered with sequelae (16.5%). Of the 12 reported MACE cases in the PsA cohort, 2 were fatal (16.7%), 9 recovered (75.0%), and 1 recovered with sequelae (8.3%). All 6 MACE cases reported in the axSpA cohort recovered (100.0%).IRs were low and stable over the treatment periods. The most common types of MACE reported in the PsO, PsA and axSpA cohorts were non-fatal myocardial infarction (PsO: IR= 0.3; PsA: IR=0.3; axSpA: IR=0.3), nonfatal stroke (PsO: IR=0.1; PsA: IR=0.2) and vascular death (PsO: IR=0.1; PsA: IR=0.1). All MACE cases were confirmed by adjudication.ConclusionThe incidence of MACE was low and stable over the IXE treatment periods examined.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMark Lebwohl Consultant of: Arcutis, Boehringer Ingelheim, Bristol Myers.Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma,Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte.Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy’s Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Corrona), Grant/research support from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara.Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development,LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, UCB Pharma, Aurinia, Moonlake, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Sergio Schwartzman Speakers bureau: AbbVie, Janssen, Lilly, Pfizer, Novartis, UCB, Consultant of: AbbVie,Janssen, Eli Lilly and Company, Pfizer, Novartis, UCB, Myriad, Regeneron, Sanofi, Stelexis, Jubilant, Teijin, National Psoriasis Foundation Medical Boar, Grant/research support from: Lilly, Carlo Salvarani Consultant of: AbbVie, Eli Lilly and Company, and Roche, Grant/research support from: Roche, Meghan Feely Shareholder of: Eli Lilly and Company, Speakers bureau: Mount Sinai, Consultant of: Mount Sinai, Hospital, NY, Eli Lilly and Company, Aerolase, Castle Biosciences, Galderma Aesthetics, Revian, Sonoma Pharmaceuticals, Suneva Medical, and Sun Pharmaceutical Industries, AAD Investment Committee, AAD Media Expert Team, AEI Leadership Network, Leonine Forum, WDS Committees: Practice Advisory, Finance and Investment, Fundraising and Philanthropic Activities, Prevention Medical Review Board, ASDS Social Media Ambassador, Grant/research support from: Eli Lilly and Company, Mount Sinai, MC Medical Group, The Dermatology and Laser Group, Windsor Dermatology, Employee of: Eli Lilly and Company, Danting Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Proton Rahman Consultant of: AbbVie, Eli Lilly and Company, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis, Kim Papp Speakers bureau: AbbVie, Amgen, Bausch Health/Valeant, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Merck,Novartis, Pfizer, Sanofi, Consultant of: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen,Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv.Therapeutics, Xencor, Grant/research support from: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen,Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv.Therapeutics, Xencor, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Regeneron, Sun Pharma, and UCB Pharma, Alice B Gottlieb Shareholder of: Xbiotech (stock options for an RA project), Consultant of: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer.Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech, Grant/research support from: AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, Andrew Blauvelt Speakers bureau: AbbVie, UCB, Consultant of: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, EcoR1, Vibliome, Grant/research support from: AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim,Bristol-Myers Squibb, Dermavant, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma Investigator (payments made to my company),
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Taylor, P. C., K. De Vlam, A. G. Bushmakin, L. Fallon, J. F. Merola, J. C. Cappelleri, M. A. Hsu, and P. J. Mease. "AB0838 IDENTIFYING MEDIATORS OF PAIN REDUCTION IN PATIENTS WITH PSORIATIC ARTHRITIS TREATED WITH TOFACITINIB: ROLE OF INFLAMMATION ASSOCIATED WITH PERIPHERAL ARTHRITIS, ENTHESITIS AND SKIN DISEASE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1724–25. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1052.
Full textAbstract:
Background:Treatment effect on pain is a priority for patients (pts) with psoriatic arthritis (PsA) and physicians. As pain is multidimensional, there is growing interest to understand the mechanisms of pain relief during treatment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Previous analyses showed that the effect of tofacitinib on pain in pts with PsA was partially mediated through improvement of inflammation as assessed by C-reactive protein (CRP) and Swollen Joint Count (SJC). Additional potential inflammation-associated mediators that might contribute to tofacitinib’s effect on pain include enthesitis and skin disease.Objectives:To describe the interrelationship between pain, tofacitinib treatment and potential inflammatory-associated outcomes, using mediation modelling.Methods:Data from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily (BID) or placebo were used; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Analyses were completed using pooled and individual study data at Months 1 and 3 (using mean scores across visits). Mediation modelling seeks to explain mechanisms underlying observed relationships between independent and dependent variables via other variables (mediators). This initial model included: treatment as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); pain, measured by Patient’s Assessment of Arthritis Pain (VAS, 0–100 mm), as the dependent (outcome) variable; mediators were: pt-reported Itch Severity Index (ISI); CRP; SJC; Psoriasis Area and Severity Index (PASI); and enthesitis, measured by Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). The final model was revised based on results of the initial model.Results:The initial model (N=329; pooled data) showed that tofacitinib treatment affects pain mainly indirectly via ISI, CRP, SJC, PASI and enthesitis (LEI), with 16.0% (p=0.53) attributable to the direct effect. The indirect effect via SJC (<1%) was not significant (p=0.99); the indirect effect via PASI was contradictory (-14.4%, p=0.10). The final model (Figure 1) excluded SJC and PASI. Analysis of the final model (N=468; pooled data) revealed that 29.5% (p=0.0579) of tofacitinib treatment effect on pain was attributable to the direct effect, and 70.5% (p<0.0001) was attributable to the indirect effect. ISI, LEI and CRP mediated 37.4% (p=0.0002), 17.8% (p=0.0157) and 15.3% (p=0.0107) of the tofacitinib treatment effect on pain, respectively. Results for individual studies were consistent with pooled data, as were those when enthesitis was represented by SPARCC in the model.Conclusion:The majority of tofacitinib treatment effect on pain in pts with PsA is collectively mediated by itch, enthesitis and CRP, with itch being the main mediator of treatment effect (~37%), using mediation modelling analyses.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Kurt de Vlam Grant/research support from: Celgene, Eli Lilly, Pfizer Inc, Consultant of: AbbVie, Eli Lilly, Galapagos, Johnson & Johnson, Novartis, Pfizer Inc, UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau
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Petrich, Adam M., Leo I. Gordon, Jeffrey R. Infante, Sumit Madan, Francis J. Giles, Halla S. Nimeiri, Jason B. Kaplan, et al. "Phase 1 Dose-Escalation Study of TAK-659, an Investigational SYK Inhibitor, in Patients (Pts) with Advanced Solid Tumor or Lymphoma Malignancies." Blood 126, no. 23 (December 3, 2015): 2693. http://dx.doi.org/10.1182/blood.v126.23.2693.2693.
Full textAbstract:
Abstract Background Spleen tyrosine kinase (SYK) is a nonreceptor cytoplasmic kinase that binds to phosphorylated immunoreceptor tyrosine-based activating motifs and mediates cellular proliferation and survival. SYK plays a key role in B-cell receptor signaling-driven tumorigenesis; thus, inhibition of SYK represents a viable therapeutic approach for various B-cell malignancies. Preclinical studies of TAK-659, an investigational, reversible SYK inhibitor, demonstrated inhibition of SYK activity and cell proliferation in vitro and dose-dependent tumor growth inhibition in vivo in lymphoma xenograft models. The primary objectives of this first-in-human phase 1 study (NCT02000934) are to determine the safety, tolerability, and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of TAK-659. Secondary objectives include evaluation of the preliminary antitumor activity and the pharmacokinetics (PK) of TAK-659. Methods Pts aged ≥18 yrs with advanced solid tumors or lymphoma, for which standard treatment was either not available or no longer effective, received oral TAK-659 daily (QD, 60-120 mg) in 28-d cycles. For MTD determination, dose escalation proceeded via a modified titration design based on dose-limiting toxicities (DLTs) or drug-related grade ≥2 adverse events (AEs) during cycle 1 (C1). Cell of origin classification data (activated B cell [ABC] vs germinal center B cell [GCB] subtype via immunohistochemistry) were collected from pts with diffuse large B-cell lymphoma (DLBCL). AEs were assessed per NCI-CTCAE v4.03. Blood samples for plasma PK assessments were collected pre-dose and at multiple times post-dose on d1 and d15 of C1. Response per RECIST v1.1 (solid tumors) and per IWG modified criteria (lymphoma) was assessed between d22 and d29 (pre-dose, d1 next cycle) of C2, C4, and C6, and then every 3 cycles. Results At data cut-off (June 15, 2015), 24 pts had been enrolled (14 solid tumor pts; 10 lymphoma pts) at 4 dose levels of TAK-659 (60, 80, 100, 120 mg). Overall, the median age was 58 years [range 43-80], 67% were male, and 58% had ≥4 prior lines of therapy. Of 10 lymphoma pts, 7 had DLBCL (5 GCB and 2 ABC subtypes) and 3 had follicular lymphoma (FL). Six pts remain on the study; 2 solid tumor and 4 lymphoma pts. The median number of TAK-659 cycles was 2 (range 1-4) for solid tumor pts and 4 (1-12) for lymphoma pts (Figure 1). C1 DLTs occurred in 5 pts; 1 pt at 60 mg (grade 3 asymptomatic aspartate aminotransferase [AST] elevation) and 4 pts at 120 mg (grade 3 and 4 asymptomatic lipase elevation, grade 3 mucositis, and grade 3 generalized edema). MTD determination is ongoing. All grade drug-related AEs occurred in 18 pts (75%) overall; the most common were fatigue (25%), elevated AST (21%), anemia (17%), and diarrhea (17%). Grade ≥3 drug-related AEs occurred in 8 pts (33%); anemia (1 pt at 60 mg, 2 pts at 120 mg), hypophosphatemia (2 pts at 80 mg), and increased lipase (2 pts at 120 mg) were seen in ≥1 pt. Four pts discontinued due to AEs (1 considered related to TAK-659, grade 3 pneumonia); 5 pts died on study (deaths were not considered related to TAK-659). Preliminary plasma PK of TAK-659 (n=24, 60-120 mg) showed rapid absorption (median Tmax 2 hrs), moderate variability in steady-state exposures (54% coefficient of variation for d15 dose-normalized AUCtau), mean peak-to-trough ratio of 4, and accumulation of 2.3-fold after repeated QD dosing for 15 d. Of 7 response-evaluable DLBCL pts, 2 pts (1 at 60 mg [GCB], 1 at 80 mg [ABC]) achieved partial responses (PRs), and a 3rd pt (at 120 mg [GCB]) achieved a PR post data cut-off (Figure 1). One GCB-DLBCL responder with multiple prior therapies including autologous hematopoietic stem cell transplantation is ongoing in C12. Two of 3 FL pts (both at 100 mg) were response-evaluable - 1 achieved a PR after 2 cycles (ongoing in C5) and 1 achieved a complete response after 2 cycles (ongoing in C4). Updated results will be presented at the meeting. Conclusions Oral TAK-659 60-100 mg QD appears to have an acceptable safety profile with an acceptable PK profile that supports continuous oral QD dosing. Early antitumor activity in DLBCL and FL pts is evident. Expansion cohorts are planned in pts with DLBCL and chronic lymphocytic leukemia. In addition, TAK-659 is also a potent FLT-3 inhibitor; a separate ongoing clinical trial is investigating the dual SYK and FLT-3 inhibitory activity of TAK-659 in relapsed/refractory acute myelogenous leukemia (NCT02323113). Disclosures Petrich: Gilead: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Spectrum Pharmaceuticals: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding. Off Label Use: This is a first-in-human phase 1 study of TAK-659, an investigational SYK inhibitor, in adult patients with advanced solid tumor or lymphoma malignancies.. Gordon:Northwestern University: Employment; Dr Leo I. Gordon: Patents & Royalties: Patent for gold nanoparticles pending. Infante:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding. Madan:Celgene: Speakers Bureau; Onyx: Speakers Bureau. Stumpo:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Zhang:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Faucette:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Shou:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment.
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Genovese, M. C., A. Lertratanakul, J. Anderson, K. Papp, W. Tillett, F. Van den Bosch, S. Tsuji, et al. "OP0223 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND INADEQUATE RESPONSE TO BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (SELECT-PSA-2): A DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE 3 TRIAL." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 139. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1229.
Full textAbstract:
Background:Upadacitinib (UPA) is an oral, reversible, JAK inhibitor approved for treatment of moderate to severe rheumatoid arthritis (RA) and currently under evaluation for treatment of psoriatic arthritis (PsA).Objectives:To assess the efficacy and safety of UPA versus placebo (PBO) in patients (pts) with PsA and prior inadequate response or intolerance to ≥1 biologic disease-modifying anti-rheumatic drug (bDMARD).Methods:In SELECT-PsA-2, pts were randomized 1:1:1 to once daily UPA 15 mg (UPA15), UPA 30 mg (UPA30), or PBO. Pts were stratified by baseline DMARD use, number of prior failed bDMARDs, and extent of psoriasis. The primary endpoint was the proportion of pts achieving ACR20 response at Wk 12. Multiplicity controlled secondary endpoints included change in HAQ-DI, FACIT-Fatigue (FACIT-F), and SF-36 Physical Component Summary (PCS) at Wk 12; static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline, PASI75, and change in Self-Assessment of Psoriasis Symptoms (SAPS) at Wk 16; and proportion of pts achieving MDA at Wk 24. Additional key secondary endpoints were ACR50 and ACR70 at Wk 12, and ACR20 at Wk 2. Treatment-emergent adverse events (TEAEs) are reported for pts who received ≥1 dose of study drug.Results:641 pts were randomized and received study drug; 54.3% were female with mean age of 53.4 years, and mean duration since PsA diagnosis of 10.1 years. 61% of pts failed 1 bDMARD, 18% failed 2 bDMARDs, and 13% failed ≥3 bDMARDs. 543 (84.6%) pts completed Wk 24 study drug.At Wk 12, a significantly greater proportion of pts receiving UPA15 and UPA30 vs PBO achieved ACR20 (56.9% and 63.8% vs 24.1%; p < .0001 for both comparisons). Statistically significant improvements were observed in the UPA15 and UPA30 arms vs PBO in all multiplicity controlled secondary endpoints, including ΔHAQ-DI (PBO, -0.10; UPA15, -0.30; UPA30, -0.41), ΔSF-36 PCS (PBO, 1.6; UPA15, 5.2; UPA30, 7.1), ΔFACIT-F (PBO, 1.3; UPA15, 5.0; UPA30, 6.1), and ΔSAPS (PBO, -1.5; UPA15, -24.4; UPA30, -29.7; p < .0001 for all endpoints;Figure 1). In addition, a greater proportion of pts achieved ACR50 and ACR70 at Wk 12 with UPA vs PBO. Generally, TEAEs were reported at similar frequencies in the PBO and UPA15 arms and at a higher frequency in the UPA30 arm (Figure 2). Numerically higher rates of serious AEs were reported in the UPA arms. Herpes zoster was more frequent with UPA30. Three malignancies occurred in each of the UPA arms. One adjudicated non-fatal myocardial infarction and one adjudicated pulmonary embolism were reported with UPA15.Conclusion:In this bDMARD-IR PsA population, UPA15 and UPA30 demonstrated significant improvements across PsA domains including improvements in joint and skin signs and symptoms vs PBO through Wk 24 with improvement observed by Wk 2. A greater percentage of pts treated with UPA achieved MDA and ACR50/70, stringent composite measures of disease control. No new safety signals were identified compared to what has been observed with UPA in RA.Disclosure of Interests:Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Apinya Lertratanakul Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jaclyn Anderson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kim Papp Grant/research support from: AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Takeda, UCB, and Valeant., Consultant of: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Speakers bureau: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Shigeyoshi Tsuji Grant/research support from: Eli Lilly, Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K., Eva Dokoupilova Grant/research support from: Eli Lilly, AbbVie, Novartis, MAURO KEISERMAN Speakers bureau: Pfizer, Abbott, Actelion, AstraZeneca, Amgen, Roche, Bristol Myers Squibb, and Janssen and has received clinical trial honoraria from Pfizer, Amgen, AstraZeneca, Anthera Pharmaceuticals, Bristol-Myers Squibb, Biogen Idec Inc, Celltrion Inc., Eli Lilly, Human Genome Sciences, Novartis, Roche, Sanofi, UCB Inc., xin wang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Sheng Zhong Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Patrick Zueger Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau
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Mease, P. J., A. Setty, K. Papp, F. Van den Bosch, S. Tsuji, M. Keiserman, K. Carter, et al. "POS1539 SAFETY AND EFFICACY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS AND INADEQUATE RESPONSE TO BIOLOGICS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PSA 2 STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1136–37. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2513.
Full textAbstract:
BackgroundThe efficacy and safety of upadacitinib (UPA) in patients (pts) with psoriatic arthritis (PsA) and inadequate response to ≥1 biologic disease-modifying antirheumatic drug (bDMARD-IR) have been demonstrated up to 56 and 104 weeks of treatment[1,2].ObjectivesTo assess the long-term safety and efficacy of UPA in bDMARD-IR pts with PsA through 152 weeks of treatment in the SELECT-PsA 2 study.MethodsPts were randomized to receive UPA 15 or 30 mg once daily (QD), or placebo (PBO) for 24 weeks, followed by blinded switch to UPA 15 or 30 mg QD for pts initially randomized to PBO. After 56 weeks, pts continued their assigned dose up to 152 weeks in an open-label extension (OLE). Following approval of the 15 mg QD dose, the protocol was amended and all pts on UPA 30 mg QD were switched to the approved dose (earliest switch at week 116). Endpoints assessed at 152 weeks included: % of pts achieving 20/50/70% improvement in American College of Rheumatology (ACR) criteria, minimal disease activity (MDA), and 75/90/100% improvement in Psoriasis Area and Severity Index, as well as patient-reported outcomes. Efficacy data were evaluated using non-responder imputation (NRI) and as-observed (AO) data (binary endpoints), and mixed effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) through 3 years (cut-off date, 05 May 2022) are also reported.ResultsOf the 641 pts randomized to receive UPA 15 or 30 mg QD, or PBO followed by UPA 15 or 30 mg QD (n=211, 218, 106, and 106, respectively), 478 entered the OLE. Improvements in efficacy outcomes with UPA observed at 561and 1042weeks were maintained through the OLE, with ACR20 achieved by 43–51% (NRI) and 79–87% (AO) of pts across treatment arms at week 152. The highest % of MDA responders at week 152 (31% [NRI] and 44% [AO]) were in the continuous UPA 15 mg arm (Table 1). UPA was well tolerated through 152 weeks, with no new safety signals identified. The overall exposure-adjusted event rates for any TEAE were higher for UPA 30 vs 15 mg (295 vs 226 events/100 PY, respectively [Figure]).ConclusionObserved improvements in the signs and symptoms of PsA with UPA were maintained through 3 years of treatment in bDMARD-IR pts. The long-term safety profile of UPA in this treatment-refractory population was consistent with its known safety profile across indications.References[1]Mease PJ, et al.Rheumatol Ther2021;8:903–919[2]Mcinnes I, et al.Rheumatol Ther2022. doi.org/10.1007/s40744-022-00499-wTable 1.Efficacy endpoints at week 152EndpointUPA 15 mg QD (n=211)UPA 30 mg QDa(n=218)PBO/UPA 15 mg QD (n=106)PBO/UPA 30 mg QDa(n=106)Proportion of patients (%)NRIAONRIAONRIAONRIAOACR20/50/7051/39/2481/60/3649/35/2279/56/3443/29/2087/60/4043/28/1879/53/36MDA3144254116411937PASI75/90/10043/31/2066/46/3041/36/2972/61/4845/34/2379/61/4241/35/3075/63/55Resolution of enthesitis (LEI=0)b3869366824762562Resolution of dactylitis (LDI=0)c4994501003410028100Change from BLMixed effect model for repeated measuresmean (95% confidence interval)Health Assessment Questionnaire – Disability Index-0.4(-0.5, -0.3)-0.5(-0.5, -0.4)-0.5(-0.6, -0.3)-0.3(-0.4, -0.2)Bath Ankylosing Spondylitis Disease Activity Indexd-2.6(-3.1, -2.1)-2.0(-2.5, -1.5)-2.3(-3.1, -1.5)-2.5(-3.2, -1.7)Ankylosing Spondylitis Disease Activity Scored-1.4(-1.6, -1.1)-1.1(-1.4, -0.9)-1.0(-1.4, -0.7)-1.2(-1.5, -0.8)aFollowing a protocol amendment, all pts on UPA 30 mg QD switched to UPA 15 mg QD (earliest switch at week 116).bBL LEI >0.cBL LDI >0.dAmong pts with psoriatic spondylitis at BL, as determined by the investigator.ACR20/50/70, 20/50/70% improvement in American College of Rheumatology Criteria; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MDA, minimal disease activity; NRI, non-responder imputation; PASI75/90/100, 75/90/100% improvement in Psoriasis Area and Severity Index; PBO, placebo; pt, patient; QD, once daily; UPA, upadacitinib.AcknowledgementsAbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation; and participated in the writing, review, and approval of the abstract. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. No honoraria or payments were made for authorship. Medical writing support was provided by Katerina Betsista, MD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsPhilip J Mease Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squib, Celgene, Galapagos, Genentech, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Arathi Setty Employee of: AbbVie, and may own stock or options, Kim Papp Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, Genentech/Roche, Janssen, Kyowa Kirin, LEO, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Filip van den Bosch Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB, Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB, Shigeyoshi Tsuji Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Roche, Novartis, Pfizer, Janssen, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Roche, Novartis, Pfizer, Janssen, and UCB, Kyle Carter Employee of: AbbVie, and may own stock or options, Reva McCaskill Employee of: AbbVie, and may own stock or options, Erin McDearmon-Blondell Employee of: AbbVie, and may own stock or options, Peter Wung Employee of: AbbVie, and may own stock or options, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Ono Pharma, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Janssen, Eli Lilly, Pfizer, and UCB.
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Ince, Bernard. "Hidden Identities, Forgotten Histories: Female Provincial Touring Artists in Britain, 1887–1900." New Theatre Quarterly 38, no. 2 (April 20, 2022): 139–50. http://dx.doi.org/10.1017/s0266464x22000045.
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Provincial touring companies of the late Victorian period, comprising mostly unknown actors and actresses, have received minimal scholarly attention until recently. The sheer number of ‘on-the-road’ artists who were employed in such enterprises from the late nineteenth century onwards increased to such an extent that to establish a framework for their individual and collective study presents significant challenges. This article addresses this problem by proposing a method, grounded in genealogy, that records the male and/or female artists of a given touring company over its full term without selective bias in order to establish a cohort of subjects for further examination. It tracks the touring companies of actor-manager Lawrence Daly, an individual unheard of today, between 1887 and 1900, the year of his death. One hundred and twenty-five female artists employed by Daly during this period are recovered, and their careers, family histories, and personal identities are subjected to statistical analysis. The conclusions drawn here not only contribute to the better understanding of the social history of non-elite female provincial artists of the late nineteenth century, but also afford the opportunity to shine a light on figures whose names, lives, and achievements are long forgotten. Further, a case is made for the method as the basis for a wide-ranging database of provincial touring companies and artists. Bernard Ince is an independent theatre historian who has contributed several articles on Victorian and Edwardian theatre to New Theatre Quarterly.
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Banerji, Versha, Nizar Abdel-Samad, Andrew Aw, Sarah-Jane Bull, Pierre-André Fournier, Nathalie Johnson, Nicole B. Laferriere, et al. "Tumor Lysis Syndrome: Incidence, Mitigation and Management in Patients with Chronic Lymphocytic Leukemia Initiating Venetoclax in Routine Clinical Practice (DEVOTE) across Canada." Blood 138, Supplement 1 (November 5, 2021): 3744. http://dx.doi.org/10.1182/blood-2021-146001.
Full textAbstract:
Abstract Patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) receiving venetoclax (VEN) are at risk of tumor lysis syndrome (TLS). This may be mitigated by implementing a 5-week ramp-up dosing schedule, use of antiuricemic agents and continuous hydration in high-risk patients. Currently, there is a lack of real-world data on the incidence of TLS in routine clinical care of R/R CLL patients treated with VEN in Canada. This is particularly the case amongst heavily pretreated patients progressing on prior ibrutinib who would be considered at high risk for aggressive disease and subsequent TLS. The DEVOTE study is a Canadian multicenter open-label study examining the real-world characteristics of patients with R/R CLL, their management with special attention to TLS mitigation measures, and their health care resource utilization and quality of life. Eligible patients were adults who had provided written informed consent, had CLL and had received ≥1 prior line of therapy, and whose physician had decided to prescribe VEN in routine clinical practice. Those participating in an interventional study were excluded. Assessments included baseline and concomitant medication use, TLS risk, clinical and laboratory assessments at baseline and ramp up visits, and measures taken to mitigate TLS. This interim analysis included 69 patients, 64 of whom completed ramp up phase. Median (range) age was 71 (39-91) years; 74% were male; 18/57 cases had del17p and 19/24 were documented as IgVH unmutated. Baseline TLS risk was low for 21 patients, medium for 37, and high for 11. Median time from last relapse to baseline assessment was 5.9 weeks. Patients had undergone a median (range) of 2 (1-7) prior lines of therapy with 63 previously treated with ibrutinib; 36 discontinued due to disease progression, 23 for intolerance, and 4 for other reasons. Ibrutinib was the last prior line of therapy in 59 patients, of whom 18 continued to take it concomitantly during VEN dose ramp up (for a median of 19 days). Four laboratory TLS events (per Howard's criteria, conservatively modified to include total calcium in place of ionized or corrected calcium) were reported in 4 patients (Table). The patients were medium (3) or high (1) TLS risk. The 2 patients with laboratory TLS at the 20mg ramp up visit (both medium TLS risk) had CLL progression on ibrutinib and were taking it concomitantly at the time of laboratory TLS. No patient developed renal dysfunction, nor required rasburicase therapy or dialysis, and all patients continued on VEN therapy. No cases of clinical TLS were reported. Antiuricemic agents were administered preemptively to 62 patients, starting a median of 7.5 days before the 20mg ramp up visit and 67 (including all high TLS risk patients) received these agents concomitant with VEN for a median of 29 days. Two patients (both medium TLS risk) did not receive an antiuricemic agent at any time during the study; neither had a measurement of elevated uric acid during the study. Uric acid > 475 μmol/L was reported at baseline for 7 patients, including 1 patient (not hospitalized) who experienced a TLS event at the 20mg ramp up visit and 2 patients with high TLS risk, neither of whom received rasburicase or experienced a TLS event. Overall, 25 patients were hospitalized at least once, all of whom were hospitalized for the 20mg ramp up visit with numbers diminishing for subsequent visits. The 44 patients who completed ramp up as out-patients included 2 patients with high TLS risk. The product monograph recommends hospitalization for high TLS risk or medium TLS risk with CrCl <80mL/min. Overall, 23 patients met this criteria, of whom only 12 were hospitalized. Thirteen patients who did not meet the criteria were hospitalized for the 20mg visit at the physician's discretion. The only characteristic associated with hospitalization was TLS risk. Most patients (87%) reached a VEN dose of 400 mg daily, 75% of whom did so in ≤5 weeks. Safety profile was consistent with previous reports (Table). In this heavily pre-treated population including a majority of patients with disease progression on ibrutinib, few cases of laboratory TLS and no clinical TLS were reported during initiation of VEN. No patient required rasburicase and some patients deemed at high risk for TLS were safely treated as outpatients. As the study was performed soon after VEN approval in Canada, patient characteristics and TLS mitigation strategies may have evolved with time. Figure 1 Figure 1. Disclosures Banerji: Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy; Gilead: Consultancy; Roche: Consultancy; Lundbeck: Consultancy. Aw: AbbVie: Honoraria; AstraZeneca: Honoraria. Bull: AbbVie: Current Employment, Current equity holder in publicly-traded company. Fournier: AbbVie: Current Employment, Current equity holder in publicly-traded company. Johnson: Merck: Consultancy; Roche: Consultancy, Honoraria; BMS: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy; AbbVie: Consultancy, Research Funding. Laferriere: AbbVie: Honoraria; Alexion: Honoraria; Amgen: Honoraria; Astellas: Honoraria; BMS: Honoraria; Gilead: Honoraria; Leo Pharma: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Teva: Honoraria. Lembo: AbbVie: Current Employment, Current equity holder in publicly-traded company. Pelizon: AbbVie: Current Employment, Current equity holder in publicly-traded company. Peters: AbbVie, Incyte: Consultancy, Honoraria. Owen: Roche: Honoraria, Research Funding; Servier: Honoraria; AbbVie: Honoraria, Research Funding; Genentech: Research Funding; Incyte: Honoraria; Merck: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pharmacyclics: Research Funding.
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Fama, Angelo, Peter Martin, Cristine Allmer, Carla Casulo, Jonathon B. Cohen, Umar Farooq, Andrew L. Feldman, et al. "Vulnerable Elders Survey-13 (VES-13) Predicts 1-Year Mortality Risk in Newly Diagnosed Non-Hodgkin Lymphoma (NHL)." Blood 134, Supplement_1 (November 13, 2019): 69. http://dx.doi.org/10.1182/blood-2019-129499.
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Introduction. The VES-13 is a simple, self-reported, function based tool originally developed to screen community-dwelling populations to identify persons age 65 years and older at risk of death and functional decline, including death in the next 12 months. The VES-13 items include patient's age, self-rated overall health status, functional limitations in physical activity, and functional disabilities in more complex activities of daily living. As part of the Lymphoma Epidemiology of Outcomes (LEO) cohort study, we collected self-reported VES-13 data at study enrollment on all participants regardless of age, and here we report on the prevalence of vulnerable status defined by the VES-13 and its association with 1-year mortality, overall, stratified at age 65 years, and in the subset of diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy. Methods. From 7/2015 to 6/2017, 3253 participants with NHL were enrolled within 6 months of their diagnosis into the LEO cohort. 2004 were evaluable on VES-13, and 1183 (59%) completed it before the initiation of therapy. VES-13 scores range from a minimum of 0 (low risk for decline) to a maximum of 10 (greatest risk for decline), and a score ≥3 was classified as vulnerable. Clinical, pathology and treatment data were abstracted using a standard protocol, and participants were contacted every 6 months for the first three years and then annually thereafter to identify outcomes. Medical records were reviewed by LEO clinicians to classify cause of death according to a standard protocol. Therapy was determined by the treating physician, and this was independent of knowledge of the VES-13 score. The association of VES-13 with 1-year mortality from date of diagnosis was estimated using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models, which also provided model c-statistics. Results. The median age of the 2004 participants in this analysis was 62 years (range 18-94); 57% were male; 54% were ≥65 years; and 28% had a normal body mass index (BMI), 1% were underweight, 35% were overweight, and 36% were obese. Clinically, 59% of participants had an aggressive subtype, 65% were stage III-IV, 24% had B-symptoms, and 11% had a performance status (PS) of ≥2. Overall, 28% of participants were classified as vulnerable (95% CI 26%-30%), with a higher prevalence among those completing the survey after initiation of therapy (38%, 95% 34%-41%) versus before initiation of therapy (22%, 95% CI 20%-24%), and a higher prevalence for those ≥65 years (32%, 95% CI 29%-34%) versus <65 (25%, 95% CI 22%-28%). During the first year of follow-up, there were 147 deaths, with 61% due to lymphoma, 14% therapy-related, 12% due to another malignancy, 3% other causes, and 10% unknown. Significant univariate predictors of 1-year mortality included vulnerable status, older age, PS 2+, stage III-IV, aggressive subtype, lower quality of life score, lower BMI, and 1 or more comorbidities, and were included the backward stepwise modeling. Vulnerable status (OR=3.26, 95% CI 2.15-4.96) was retained in the final model that also included age, PS, stage, and NHL subtype (Table), with a model c-statistic of 0.81. As shown in the Table, these associations were similar whether VES-13 was assessed before (c-statistic 0.77) or after (c-statistic 0.81) initiation of therapy. After adjustment for age, PS, stage and NHL subtype, vulnerable status predicted 1-year mortality in participants ≥65 years (OR=1.96, 95% CI 1.15-3.36; model c-statistic 0.80) as well as <65 years (OR=6.38, 95% CI 3.07-13.3; model c-statistic 0.83). Finally, in the DLBCL patients treated with immunochemotherapy (N=521), vulnerable status (38% of patients) also predicted 1-year mortality (OR=2.11, 95% CI 1.05-4.26) after adjusting for age, PS and stage (model c-statistic 0.78). Conclusion. Based on a self-administered VES-13, 28% of newly diagnosed NHL patients in the LEO cohort were classified as vulnerable, including 25% of those <65 years, and vulnerable status was a strong predictor of 1-year-mortality, even in the subset of DLBCL patients treated with presumed curative intent. These results highlight the potential value of screening for vulnerable status overall and across a wider age spectrum in order to optimize patient management and reduce early mortality. Disclosures Martin: Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Teneobio: Consultancy. Casulo:Gilead: Honoraria, Other: Travel, accommodation, expenses; Celgene: Research Funding; Roche: Other: Travel, accommodation, expenses. Cohen:Takeda Pharmaceuticals North America, Inc.: Research Funding; Bristol-Meyers Squibb Company: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; UNUM: Research Funding; Gilead/Kite: Consultancy; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding. Farooq:Kite Pharma: Research Funding; Celgene: Honoraria. Friedberg:Acerta: Other: Data & Safety Monitoring Committee; Bayer: Honoraria, Other: Data & Safety Monitoring Committee. Kahl:Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; BeiGene: Consultancy; TG Therapeutics: Consultancy. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Maurer:Nanostring: Research Funding; Celgene: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees. Nastoupil:Spectrum: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding. Rutherford:Heron: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Juno Therapeutics Inc: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Flowers:National Cancer Institute: Research Funding; BeiGene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Spectrum: Consultancy; Karyopharm: Consultancy; Acerta: Research Funding; TG Therapeutics: Research Funding; Millenium/Takeda: Research Funding; AstraZeneca: Consultancy; Optimum Rx: Consultancy; V Foundation: Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Denovo Biopharma: Consultancy; Gilead: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding.
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Mcgonagle, D., A. Kavanaugh, I. Mcinnes, L. E. Kristensen, J. F. Merola, B. Strober, R. Bolce, et al. "POS1526 TREATMENT EFFECTS OF IXEKIZUMAB AND ADALIMUMAB AT THE INDIVIDUAL DIGIT LEVEL WITH NAIL AND DISTAL INTERPHALANGEAL JOINT INVOLVEMENT IN PATIENTS WITH PSORIATIC ARTHRITIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1124–25. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5.
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BackgroundThe prevalence of nail disease in patients with psoriatic arthritis (PsA) ranges between 41% and 93%[1]. Psoriatic nail disease is intimately linked to adjacent distal interphalangeal joint (DIP) disease, and it is important to ascertain whether DIP-nail complex behaves differently under different biological therapies.ObjectivesThe aim of this analysis was to comparatively assess the effect of ixekizumab (IXE) and adalimumab (ADA) at the individual digit level in improving nail and joint disease, in patients with PsA and concomitant nail involvement.MethodsThis post hoc analysis included patients from SPIRIT-H2H (NCT03151551) treated with either IXE or ADA who had baseline nail disease (NAPSI total score >0) and DIP involvement in at least one simultaneous digit, with either tenderness, swelling or both, at the individual digit level for each hand. Proportions of patients having a NAPSI total score >0 and proportions of patients having DIP involvement (tenderness or swelling) were evaluated at baseline and Week 24; post-baseline assessments were compared between treatment arms using Fisher’s exact test.ResultsOf the intent-to-treat population of SPIRIT-H2H (N=566), 354 patients had a NAPSI total score >0 and DIP involvement (swelling or tenderness) in at least 1 digit simultaneously at baseline (IXE, N=186 and ADA, N=168). Of these patients, significantly fewer IXE- vs. ADA-treated patients had a NAPSI total score of > 0 at Week 24 (p<0.05 for 9/10 digits; Table 1) and numerically fewer IXE- vs. ADA treated patients had DIP involvement at Week 24 across all 10 digits (p<0.05 for 4/10 digits; Table 1). Numerically fewer IXE- vs. ADA-treated patients had joint tenderness at Week 24. A similar pattern of improvement was seen out to Week 52 (Table 1).ConclusionIn this analysis, in patients from SPIRIT-H2H with psoriatic arthritis who had nail involvement and DIP involvement at baseline, patients treated with IXE had less nail involvement, less DIP involvement and less tenderness compared to those treated with ADA at Week 24.Reference[1]Ogdie A. and Weiss P. Rheum Dis Clin North Am. 2016;41(4): 545–568Table 1.The proportion (%) of patients with (A) NAPSI >0 and (B) DIP involvement (tenderness or swelling) at Week 24 at the individual digit level among patients treated with either IXE (N=186) or ADA (N=168) who had NAPSI >0 and distal interphalangeal joint involvement at baseline. *p<0.05, †p<0.1, ‡p<0.001 vs ADA, Fisher’s Exact test p-value.Left HandRight HandLittleRingMiddleForeThumbThumbForeMiddleRingLittleNAPSI >0 (%)Week 24IXE Q4WADA Q2W17.0*27.917.6*27.914.2†25.515.3†27.311.4†23.615.3†27.313.6†25.515.3*26.715.9†26.713.121.2p-value*0.01910.02760.00970.00790.00390.00790.00620.01130.01690.0602Week 52IXE Q4WADA Q2W10.921.410.316.610.915.910.317.29.114.512.119.39.717.210.919.37.312.410.914.5p-value*0.01280.13040.24000.09580.15470.08590.06410.05380.17700.3924DIP involvement (%) Week 24IXE Q4W10.711.315.819.817.515.820.921.511.910.7ADA Q2W15.220.025.527.324.822.428.530.917.018.8p-value*0.25900.03570.03190.12490.11150.13070.13120.04950.21680.0459Week 52IXE Q4WADA Q2W1.22.82.44.87.28.35.45.51.26.21.84.14.27.64.29.74.84.11.24.1p-value*0.42280.35780.83221.00000.02730.31280.23050.07031.00000.1521Data are presented as proportion of patients (%). *Fisher’s Exact test p-value. Abbreviations: ADA, adalimumab; IXE, ixekizumab.Acknowledgements:NIL.Disclosure of InterestsDennis McGonagle Speakers bureau: AbbVie, Eli Lilly and Company, Incyte, Janssen, Regeneron, Sanofi-Genzyme, Consultant of: AbbVie, Alumis, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol-Myers-Squibb, Connect Biopharma, Dermavant, EPI Health, Evelo Biosciences, Janssen, Leo, Eli Lilly and Company, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Sanofi-Genzyme, Union Therapeutics, Ventyxbio, vTv Therapeutics, CorEvitas/Corrona Psoriasis Registry, Arthur Kavanaugh Speakers bureau: Pfizer, UCB, Abbvie, Consultant of: Abbvie, Eli Lilly and Company, Janssen, Novartis, BMS UCB, Grant/research support from: AbbVie, Pfizer, Iain McInnes Consultant of: Abbvie, Amgen, BMS, Causeway Therapeutics, Cabaletta, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, Sanofi, UCB, Evelo, Compugen, AstraZeneca, Moonlake, Grant/research support from: BMS, Eli Lilly and Company, Janssen, Novartis, UCB, AstraZeneca, Lars Erik Kristensen Speakers bureau: Abbvie, Amgen, UCB, Galapagos, Novartis, Eli Lilly and Company, Pfizer, Janssen pharmaceutical, Zuellig pharma, Consultant of: Abbvie, Amgen, UCB, Galapagos, Novartis, Eli Lilly and Company, Pfizer, Janssen pharmaceutical, Grant/research support from: Abbvie, Amgen, UCB, Galapagos, Novartis, Eli Lilly and Company, Pfizer, Janssen pharmaceutical, Joseph F. Merola Speakers bureau: Novartis, Eli Lilly and Company, UCB, Consultant of: Abbvie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB, Celgene, Biogen, Pfizer, and Leo Pharma. (ALL honoraria received), Grant/research support from: IDEC, Pfizer, Sanofi Regeneron, Incyte, Novartis. All funds paid to Brigham and Women’s Hospital., Bruce Strober Speakers bureau: AbbVie, Arcutis, Dermavant, Eli Lilly and Company, Incyte, Janssen, Regeneron, Sanofi-Genzyme, Consultant of: AbbVie, Alumis, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol-Myers-Squibb, Connect Biopharma, Dermavant, Evelo Biosciences, Janssen, Leo, Eli Lilly, and Company Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Sanofi-Genzyme, Union Therapeutics, Ventyxbio, vTv Therapeutics, Rebecca Bolce Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jeffrey Lisse Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jennifer Pustizzi Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christopher T. Ritchlin Speakers bureau: Abbvie, Eli Lilly and Company, Pfizer, UCB, Consultant of: AbbVie, Janssen, Novartis, BMS,UCB, Grant/research support from: AbbVie, Pfizer.
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Gardner, S. J., G. G. Swinerd, and A. K. Ward. "The Design of a Small Satellite for Earth Observation." Proceedings of the Institution of Mechanical Engineers, Part G: Journal of Aerospace Engineering 210, no. 4 (October 1996): 323–32. http://dx.doi.org/10.1243/pime_proc_1996_210_377_02.
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The concept of the Teaching Company Scheme Satellite (TuCSAT), has been developed to meet the requirements of the Earth observation user community for inexpensive and flexible opportunities to launch remote sensing instruments into low earth orbit (LEO). This paper describes the satellite design process, together with the philosophy behind the selection of a baseline mission. The satellite is shown to demonstrate the ability to meet a wide range of requirements within a strict low mass and low cost philosophy, while making use of currently available technology in order to achieve the design aims.
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Wei, Yuyang. "Marketing Strategy Analysis in the Digital Era Taking Pinduoduo as an Example." Advances in Economics, Management and Political Sciences 79, no. 1 (April 26, 2024): 44–49. http://dx.doi.org/10.54254/2754-1169/79/20241769.
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In this study, the researcher will assess the marketing strategy analysis of Pinduoduo, a Chinese e-commerce giant that, over the past few years, has gained prominence and increased its market share against traditional e-commerce companies such as Alibaba and JD.com. In this study, the researcher will examine the effectiveness of the evolving online marketplace, focusing on the companys unique business model and strategies such as time-limited instant kills and social media marketing to develop a better understanding of the impact and success of Pinduoduos approach. The methodological approach that the researcher will use is a comprehensive literature review and the SWOT model to understand Pinduoduos digital marketing strategies. The literature review approach will focus on the core business model of the company, while the SWOT model will be instrumental in analyzing market positioning and segmentation. The key questions in this study include: conducting an assessment of the efficacy of Pinduoduos marketing plan; understanding its digital marketing trends; and drawing insights from global success stories in the industry. Pinduoduos marketing strategies that have led the company to effectively engage users, specifically those from low-tier cities, include time-limited instant kills, daily cash rewards, and subsidies. The SWOT analysis has helped the company identify strengths, such as market differentiation, and weaknesses, such as high unit prices. In conclusion, Pinduoduos success will be based on its ability to successfully navigate the sinking market and its successful utilization of its strategic innovations, making it a formidable player in the digital era.
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King, Wayne. "Introduction: Frontiers of Electron Microscopy in Materials Science." Microscopy and Microanalysis 11, no. 5 (September 28, 2005): 377. http://dx.doi.org/10.1017/s1431927605050725.
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The Ninth Frontiers of Electron Microscopy in Materials Science Conference (FEMMS 2003) was held October 5–10, 2003 at the Claremont Resort and Spa in Berkeley, CA. Major sponsors for this meeting included Lawrence Livermore National Laboratory, Argonne National Laboratory, Lawrence Berkeley National Laboratory, Brookhaven National Laboratory, Frederick Seitz Materials Research Laboratory, Oak Ridge National Laboratory, National Science Foundation, and University of California at Davis. Sponsors also included LEO Electron Microscopy Ltd. (Carl Zeiss SMT), E. A. Fischione, Inc., Gatan, Inc., Thermo NORAN (Thermo Electron Corp.), FEI Company, Hitachi-HHTA, JEOL USA, Inc., Seiko Instruments, and CEOS GmbH.
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Andarani, Pertiwi, Winardi Dwi Nugraha, Desinta Sawitri, and Wiwik Budiawan. "Life-Cycle Assessment of Crude Palm Oil Produced at Mill J, PT XYZ, Sumatera Island using Eco-indicator 99." MATEC Web of Conferences 159 (2018): 01028. http://dx.doi.org/10.1051/matecconf/201815901028.
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The Crude Palm Oil industry has now become the largest agricultural industry in Indonesia. Nevertheless, the growth of CPO industry could also bring negative impacts on the environment if the company does not control their emissions and discharges properly. Life-cycle Assessment (LCA) is one of the tools that can assess the environmental impacts due to CPO production activities. This study aims to assess the potential environmental impacts arising from the CPO production system at Mill J, PT XYZ, Sumatera Island by using Eco-indicator 99. Based on this study, in 2015, the process in plantation and mill contributed to climate change category was 0.013 DALY or after normalized 202 Pt. Meanwhile, the land use category has 395 PDF*m2yr or 30.8 Pt. Meanwhile, all of the other categories were less than 30.8 Pt, hence, the highest impact of this CPO production system is climate change at the activities in industrial estate (fertilizers usage) and industry (emitted from waste water of palm oil mill).
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Gordon, K. B., A. Blauvelt, H. Bachelez, B. Kaplan, W. Koetse, L. Drogaris, R. Sinvhal, and K. Papp. "POS1023 LONG-TERM SAFETY OF RISANKIZUMAB IN PATIENTS WITH PSORIATIC DISEASE: FINDINGS FROM INTEGRATED ANALYSES OF 17 CLINICAL TRIALS IN PSORIASIS AND 4 IN PSORIATIC ARTHRITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 823.1–823. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1185.
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BackgroundRisankizumab, an interleukin-23 inhibitor, was efficacious and well tolerated in phase 2 and 3 clinical studies in patients with psoriatic disease.ObjectivesTo report long-term risankizumab safety in patients with psoriatic disease.MethodsRisankizumab safety data to March 25, 2021 were pooled from 17 phase 1–3 clinical trials in plaque psoriasis (PsO) and 4 phase 2/3 trials in psoriatic arthritis (PsA). Adverse events (AEs) of safety interest were reported for patients receiving ≥1 dose risankizumab.ResultsAmong 3197 patients with PsO (9982.6 patient years’ [PY] exposure; median (range) treatment duration, 3.7 years [1 day–6.9 years]) and 1542 patients with PsA (1594.9 PY; 1.0 year [84 days–2.0 years]), rates of treatment-emergent AEs (158.3 and 160.8 events (E)/100PY), serious AEs (7.6 and 8.4 E/100PY) and AEs leading to discontinuation (1.9 and 2.3 E/100PY) were similar. Nasopharyngitis (PsO 14.5 E/100PY, PsA 7.9 E/100PY) and upper respiratory infection (PsO 7.8 E/100PY, PsA 5.6 E/100PY) were the most common infections; sepsis and pneumonia for PsO (0.1 E/100PY each) and COVID-19 for PsA (0.4 E/100PY) were the most common serious infections. Rates of opportunistic fungal infections were <0.1 and 0.1 E/100PY in PsO/PsA patients. Rates of non-melanoma skin cancer (NMSC) were 0.7 and 0.4 E/100PY, and malignant tumors excluding NMSC were 0.6 and 0.3 E/100PY in PsO/PsA patients. Rates of major adverse cardiovascular events were 0.5 and 0.4 E/100PY in PsO/PsA patients.ConclusionRates of AEs of safety interest remained low in this largest and longest safety reporting for risankizumab to date, supporting the safety of risankizumab for the long-term treatment of patients with psoriatic disease.References[1]Gordon KB, et al. Lancet. 2018;392(10148):650-61.[2]Reich K, et al. Lancet. 2019;394(10198):576-86.[3]Blauvelt A, et al. JAMA Dermatol. 2020;156(6):649-58.AcknowledgementsAbbVie funded the study, contributed to its design and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Moira Hudson, PhD, and Janet Matsuura, PhD, of ICON (North Wales, PA, USA) and was funded by AbbVie Inc.Disclosure of InterestsKenneth B. Gordon Consultant of: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi-Aventis, Sun, and UCB, Grant/research support from: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi-Aventis, Sun, and UCB, Andrew Blauvelt Consultant of: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma, Grant/research support from: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma, Hervé Bachelez Speakers bureau: AbbVie, Almirall, Amgen, Bayer, Baxalta, Biocad, Boehringer Ingelheim, Celgene, Dermavant, Eli Lilly, Janssen, Leo Pharma, Menarini, MSD, Novartis, Pfizer, Pierre Fabre, Sandoz, Sun Pharmaceuticals, and UCB, Consultant of: AbbVie, Almirall, Amgen, Bayer, Baxalta, Biocad, Boehringer Ingelheim, Celgene, Dermavant, Eli Lilly, Janssen, Leo Pharma, Menarini, MSD, Novartis, Pfizer, Pierre Fabre, Sandoz, Sun Pharmaceuticals, and UCB, Grant/research support from: AbbVie, Almirall, Amgen, Bayer, Baxalta, Biocad, Boehringer Ingelheim, Celgene, Dermavant, Eli Lilly, Janssen, Leo Pharma, Menarini, MSD, Novartis, Pfizer, Pierre Fabre, Sandoz, Sun Pharmaceuticals, and UCB, Blair Kaplan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Willem Koetse Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Leonidas Drogaris Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ranjeeta Sinvhal Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kim Papp Speakers bureau: AbbVie, Amgen, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Botanix, Bristol-Myers Squibb, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, Meiji Sika Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Mitsubishi, Novartis, Pfizer, Regeneron, Roche, Samsung Biopepis, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Amgen, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Botanix, Bristol-Myers Squibb, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, Meiji Sika Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Mitsubishi, Novartis, Pfizer, Regeneron, Roche, Samsung Biopepis, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Grant/research support from: AbbVie, Amgen, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Botanix, Bristol-Myers Squibb, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, Meiji Sika Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Mitsubishi, Novartis, Pfizer, Regeneron, Roche, Samsung Biopepis, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant
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Winthrop, K., L. Calabrese, F. Van den Bosch, K. Yamaoka, C. Selmi, Y. Song, B. Hendrickson, I. Lagunes-Galindo, and I. Mcinnes. "FRI0141 CHARACTERIZATION OF SERIOUS INFECTIONS WITH UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 654–55. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2761.
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Background:Upadacitinib (UPA) is a selective and reversible Janus kinase (JAK) inhibitor with an approved dose of 15 mg once daily (QD) for the treatment of rheumatoid arthritis (RA). Patients (pts) receiving JAK inhibitors have been reported to be at increased risk of developing serious infection events (SIE) and opportunistic infections (OI).Objectives:To evaluate the incidence of SIEs and OIs in pts with RA receiving UPA and active comparators in the Phase 3 SELECT clinical trial program.Methods:The exposure-adjusted event rate (EAER) per 100 patient-years (E/100 PY) of SIEs and OIs was determined in pts receiving UPA in five randomized Phase 3 trials (SELECT-EARLY, SELECT-MONOTHERAPY, SELECT-NEXT, SELECT-COMPARE, and SELECT-BEYOND), of which four evaluated both UPA 15 mg and 30 mg QD doses and one (SELECT-COMPARE) evaluated only UPA 15 mg QD. Incidences of SIEs and OIs were also determined in pts receiving adalimumab (ADA) + methotrexate (MTX) in SELECT-COMPARE and MTX monotherapy in SELECT-EARLY. Data were analyzed descriptively, with no statistical comparisons between groups or doses. Risk factors for SIEs were determined using a univariate Cox regression model. The data cut-off was June 30, 2019.Results:Overall, 2629 pts who received UPA 15 mg, 1204 pts who received UPA 30 mg, 579 pts who received ADA + MTX, and 314 pts who received MTX monotherapy were included in this analysis. The EAERs (E/100 PYs [95% CI]) of SIEs were 3.2 (2.7–3.7) in the UPA 15 mg group, 5.7 (4.8–6.8) in the UPA 30 mg group, 3.9 (2.6–5.6) in pts receiving ADA + MTX, and 3.1 (1.7–5.2) in pts receiving MTX monotherapy. Pneumonia was the most common SIE, with EAERs (E/100 PYs [95% CI]) of 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.7 (0.2–1.5), and 0.7 (0.1–1.9) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Rates of OIs (including oral candidiasis and disseminated herpes zoster [HZ]) (E/100 PYs [95% CI]) were 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.4 (0.1–1.1), and 0 (0–0) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Oral candidiasis was the most frequent OI with EAERs (E/100 PYs [95% CI]) of 0.4 (0.2–0.6) in the UPA 15 mg group, 0.6 (0.3–1.0) in the UPA 30 mg group, 0.4 (0.1–1.1) in the ADA + MTX group, and 0 (0–0) in the MTX monotherapy group. Serious adverse events of HZ were only reported in the UPA groups (0.2 E/100 PYs [95% CI: 0.1–0.3] and 0.6 E/100 PYs [95% CI: 0.4–1.1] in the UPA 15 mg and 30 mg groups, respectively). Overall, there were 3 (4 coded events), 3, 1, and 0 pts who had active tuberculosis events in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Risk factors for SIEs are shown in the Figure. For both UPA doses, age ≥75 years and smoking were noted to have hazard ratios >1.Conclusion:The incidence rate of SIEs and OIs was higher in the UPA 30 mg group than the UPA 15 mg group. SIEs observed with UPA 15 mg were similar to that seen with ADA although the rates of HZ were higher on UPA. Pts with RA who are ≥75 years old and/or smokers may be at higher risk than other pts with RA for SIEs while receiving UPA.Figure.Univariate analysis of SIE risk factorsDisclosure of Interests:Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Kunihiro Yamaoka Speakers bureau: AbbVie GK, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Mitsubishi-Tanabe Pharma Corporation, Pfizer Japan Inc., and Takeda Pharmaceutical Company Ltd, Carlo Selmi Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Celgene, and Leo Pharma, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and Sanofi-Regeneron, Speakers bureau: AbbVie, Aesku, Alfa-Wassermann, Bristol-Myers Squibb, Biogen, Celgene, Eli-Lilly, Grifols, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB Pharma, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Barbara Hendrickson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ivan Lagunes-Galindo Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB
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Nikanov, Aleksandr N., Valeriy P. Chashchin, Yuliya A. Novikova, Andrey B. Gudkov, and Olga N. Popova. "Manufacturing-conditioned morbidity among non-ferrous workers in pyro-metallurgic way of nickel production." Russian Journal of Occupational Health and Industrial Ecology 61, no. 5 (July 12, 2021): 305–10. http://dx.doi.org/10.31089/1026-9428-2021-61-5-305-310.
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Introduction. Preserving and strengthening the health of the working population is one of the priority tasks in the Russian Federation. According to the "Concept of the Demographic Policy of the Russian Federation for the period up to 2025", approved by Decree of the President of the Russian Federation No. 135 of 09.10.2007, measures to reduce the mortality rate of the population, primarily citizens of working age, should include measures to reduce the mortality rate and injuries from industrial accidents and occupational diseases. The study aims to assess the relationship of health disorders with work for certain classes of diseases and the indicator of loss of life years, adjusted for the disability of workers (DALY-disability-adjusted life years), shops of pyrometallurgical nickel refining. Materials and methods. We performed a study on JSC "Kola Mining and Metallurgical Company" (JSC "Kola MMC"), which produces and processes copper-nickel ores located in the European part of the Arctic zone of the Russian Federation (Murmansk Region), which makes and processes copper-nickel ores. To assess the relationship of health disorders with work, we used the results of mandatory periodic medical examinations of 2113 employees engaged in pyrometallurgical refining of nickel and copper. Results. In the context of individual classes of diseases, experts established a statistically significant decrease in the incidence of diseases of the nervous system, skin and subcutaneous tissue, musculoskeletal system, and conditions of the genitourinary system. The conducted assessment of the connection of these health disorders with working conditions in workers of pyrometallurgical production of nickel and copper showed the presence of an average degree of contact with the impact on the body of a complex of harmful production factors of such health disorders as diseases of the nervous system, skin and subcutaneous tissue, musculoskeletal and genitourinary systems. We evaluated the effectiveness of the measures carried out using the DALY-analysis method. As a result, the researchers found a reduction in this total indicator of health loss among workers of pyrometallurgical refined nickel from 218.8 to 184.6 years (by 17.8%). Conclusions. A comprehensive assessment of health losses by the DALY analysis method indicates a significant reduction in the burden of diseases among workers of pyrometallurgical nickel refining by 15.6%, including among men - by 12.5%, among women - by 28.3%. The economic efficiency of the implemented wellness program in JSC "Kola MMC" showed that the total prevented economic damage due to reducing diseases associated with labor activity amounted to 119.3 thousand rubles per employee of metallurgical production on average for the year. The prevented economic damage resulting from the reduction of occupational diseases per employee amounted to 10.4 thousand rubles per year.
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Kim, Ik, Ki-jung Hong, Ji-yeon Gho, and Tak Hur. "A Study on the Integration of Working Environment into Life Cycle Assessment." Korean Journal of Life Cycle Assessment 5, no. 1 (April 2004): 69–76. http://dx.doi.org/10.62765/kjlca.2004.5.1.69.
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A conventional life cycle assessment (LCA) framework mainly evaluates the environmental impacts associated with inputs and outputs from/to external environment of a product system. However the inputs and outputs generated from a facility influence not only the external environment but also the working environment. Therefore, this study developed the methodology that could integrates the working environment into a conventional LCA framework. It established the general requirements for adjusting the levels of the system boundary and category indicators in order to integrate appropriately the impacts of both the working environment and the external environment which have the different characteristics. Thus, this study introduced Input Output Analysis (IOA) technique in order to extend the system boundary to the life cycle of a product system, and applied the category indicator such as the number of Disability Adjusted Life Years (DALY), the Potentially Affected Fraction (PAF) and Lost Work Days (LWD) in order to assess the impacts of end point level. A case study of a petrochemical company in Korea was provided as an example for illustrating the feasibility of the methodology developed in this study.
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Simpson, Eric, Christian Fenske, Alvin Li, Zach Dawson, Yolanda Muñoz Maldonado, Kaylee Ho, Kayla Callahan, et al. "Patients with Atopic Dermatitis Not on Systemic Therapy have High Rates of Severe, Uncontrolled Disease, and Considerable Impact on Quality of Life." SKIN The Journal of Cutaneous Medicine 8, no. 1 (January 16, 2024): s330. http://dx.doi.org/10.25251/skin.8.supp.330.
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Patients with atopic dermatitis not on systemic therapy have high rates of severe, uncontrolled disease and considerable impact on quality of life
Eric Simpson1, Christian Fenske2, Alvin Li3, Zach Dawson2, Yolanda Muñoz Maldonado3, Kaylee Ho3, Kayla Callahan3, Linda Stein Gold4, Seemal Desai5, Alexandra Golant6, Douglas DiRuggiero7, Jonathan I Silverberg8
1Oregon Health & Science University, Portland, Oregon, USA; 2Eli Lilly and Company, Indianapolis, USA; 3CorEvitas LLC, Waltham, Massachusetts, USA; 4Henry Ford Health System, Michigan, USA; 5Innovative Dermatology, PA, Texas, USA; 5The University of Texas Southwestern Medical, Dallas, Texas, USA; 6Icahn School of Medicine at Mount Sinai, New York, USA; 7Skin Cancer and Cosmetic Dermatology Center, Rome, Georgia, USA; 8George Washington University School of Medicine and Health Sciences, Washington, DC, USA
Background: Decision to initiate a new systemic therapy (ST) among patients with atopic dermatitis (AD) is complex. This cross-sectional study explored overall disease burden, sociodemographic and clinical characteristics, and disease activity among patients with moderate-to-severe AD.
Methods: Adult patients with AD who had a vIGA-ADTM score ≥3 and Eczema Area Severity Index (EASI) score ≥12 at enrollment were identified from the prospective, longitudinal CorEvitas AD Registry between 07/21/2020 and 12/31/2022. Included patients were newly prescribed an eligible ST (ST group) or not prescribed an eligible ST (non-ST group) at enrollment. Patients on ST before enrollment were excluded. Sociodemographic characteristics, disease features, severity measures (vIGA-ADTM [0–4]; body surface area (BSA) [0–100%]; EASI [0–72]), and patient-reported outcomes (PROs) were assessed. PROs included Dermatology Life Quality Index (DLQI) [0-30], Itch/Pruritus Numeric Rating Scale [0-10], Patient-Oriented Eczema Measure (POEM) [0-26], and AD Control Tool (ADCT) [<7 controlled, >7 not controlled]. Differences in means or proportions of characteristics among ST and non-ST groups were summarized using effect sizes (ES).
Results: The study included 673 (mean age=50.7 years, 55.6% female) patients who were newly prescribed ST and 229 (47.8 years, 51.3%) who were not prescribed ST. The overall distribution of race (Whites 70.4% vs. 60.5%, Asians 8.6% vs. 17.5%, Black 13.7% vs. 8.3%, Other 7.3% vs. 13.6%; ES=0.17) and geographic region (West 8.5% vs. 28.4%, South 32.1% vs. 15.7%; ES=0.27) had small differences between the ST and non-ST groups. More patients (n=402 [59.7%]) in the ST group had severe AD (vIGA-ADTM=4), whereas moderate AD (vIGA-ADTM=3) was more common (n=137 [59.8%]) in the non-ST group. Higher disease severity was reported in the ST group versus non-ST group: BSA (mean [SD]: 41.6% [17.1] vs. 31.5% [16.0]; ES=0.61) and EASI (24.3 [10.1] vs. 19.8 [8.6]; ES=0.47). Mean [SD] PRO measures were also higher in the ST group compared to non-ST group: DLQI (11.7 [7.5] vs. 10.4 [7.9]; ES=0.17), mean peak pruritus in the past 24 hours (6.8 [2.9] vs. 6.1 [3.1]; ES=0.25), POEM (17.8 [7.1] vs. 16.6 [7.5]; ES=0.17), and ADCT (14.4 [6.1] vs. 13.0 [6.7]; ES=0.21).
Conclusion: Patients not initiating ST have high rates of severe, uncontrolled AD, and considerable burden from their disease, indicating potential delayed or undertreatment. Understanding the factors that influence the decision to escalate therapy in systemic-eligible patients is important for improving care of AD.
Disclosures
Eric Simpson: Dr. Simpson reports personal fees from Advances in Cosmetic Medical Derm Hawaii LLC, AbbVie, Amgen, AOBiome LLC, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Boehringer-Ingelheim USA, Inc., Boston Consulting Group, Bristol Myers Squibb – BMS, Collective Acumen LLC (CA), CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, ExcerptaMedica, FIDE, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Johnson & Johnson, Kyowa Kirin Pharmaceutical Development, Leo Pharma, Medscape LLC, Merck, MauiDerm, MLG Operating, MJH holding, Pfizer, Physicians World LLC, PRImE, Regeneron, Revolutionizing Atopic Dermatitis Inc., Roivant, Sanofi-Genzyme, Trevi therapeutics, Valeant, Vindico Medical education, WebMD. Dr. Simpson reports grants (or serves as Principal investigator role) from AbbVie, Acrotech Biopharma Inc., Amgen, Arcutis, Aslan, Castle Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, National Jewish Health, Leo, Pfizer, Regeneron, Sanofi, and Target RWE. These potential conflicts of interest have been reviewed and managed by OHSU.
Christian Fenske: Employment and stockholder, Eli Lilly and Company.
Alvin Li: Employee of CorEvitas, LLC and stockholder, Eli Lilly and Company.
Zach Dawson: Employment and stockholder, Eli Lilly and Company.
Yolanda Muñoz Maldonado: Employee of CorEvitas, LLC.
Kaylee Ho: Employee of CorEvitas, LLC.
Kayla Callahan: Employee of CorEvitas, LLC and stockholder, Eli Lilly and Company.
Linda Stein Gold: Investigator, advisor and/or speaker for Lilly, BMS, UCB, Pfizer, Sanofi, Regeneron, Dermavant, Arcutis, Sun, Incyte, Leo, Aslan.
Seemal Desai: Dr. Desai is currently performing paid consulting services. He has previously been an advisor for Lilly and also performed consulting and/or clinical for multiple organizations.
Alexandra Golant: Dr. Golant has received consulting or speaker fees from: Regeneron, Sanofi, AbbVie, Incyte, Dermavant, Lilly, Leo Pharma, Arcutis, Janssen, Amgen, Pfizer.
Douglas DiRuggiero: Industry speaker bureau and advisory boards: AbbVie, Amgen, Arcutis, BMS, Incyte, Janssen, Lilly, Novartis, Sanofi/Regeneron, UCB.
Jonathan I. Silverberg: Jonathan Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, AOBiome, Arcutis, Alamar, Amgen, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon, Union; speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme; institution received grants from Galderma, Pfizer.
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Radkiewicz, Małgorzata. "Maria Hirszbein: An (In)visible Figure of Polish Cinema of the 1920s and 1930s." Camera Obscura: Feminism, Culture, and Media Studies 36, no. 3 (December 1, 2021): 61–83. http://dx.doi.org/10.1215/02705346-9349357.
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Abstract This article examines the career of the Polish film producer Maria Hirszbein (1889–1939/1942) in relation to the development of interwar Polish cinema, including Yiddish films, and the modern idea of a “New Woman.” Investigating Hirszbein's activities as the successful manager of her company, Leo-Film, and as cofounder and member of the Polish film producers’ unions, the article explores her professional accomplishments and innovative work style, which was based on teamwork and promoting young, talented actors, creative directors, and screenwriters sensitive to social issues. In reconstructing Hirszbein's professional biography, the text combines different sources such as press reports, film reviews, photographs from the collection of the Polish National Film Archive (FINA), and data collected by the Institute of Jewish History in Warsaw.
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Kristensen, L. E., F. Behrens, L. Puig, A. Reich, T. Holzkaemper, A. Brnabic, K. Ng, S. Liu Leage, C. Schuster, and A. Pinter. "AB0879 Interim analysis of baseline characteristics and 12-week outcomes for a subset of patients with moderate-to-severe plaque psoriasis and psoriatic arthritis from the Psoriasis Study of Health Outcomes." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1562. http://dx.doi.org/10.1136/annrheumdis-2022-eular.166.
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BackgroundApproximately 30% of patients (pts) with plaque psoriasis (PsO) develop psoriatic arthritis (PsA)1, which is associated with high Psoriasis Area and Severity Index (PASI) and nail involvement. The Psoriasis Study of Health Outcomes (PSoHO) is a 3-year (yr), international, prospective, observational cohort study comparing the effectiveness of anti-IL-17A biologics to all other approved biologics in pts with moderate-to-severe PsO.ObjectivesThis interim subset analysis describes the baseline characteristics and Week 12 (W12) effectiveness in pts with moderate-to-severe PsO and PsA in PSoHO.MethodsAdults with moderate-to-severe PsO for ≥6 months who initiated/switched biologic treatment during routine medical care were enrolled. PsA diagnosis was recorded by the dermatologists based on the medical history and/or information provided by the patient. W12 effectiveness was assessed by the proportion of pts achieving almost clear or clear skin defined by ≥90% improvement in PASI, affected Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), and Patient Global Assessment of Disease Severity (PatGA). Musculoskeletal endpoints were not collected. Data were analysed descriptively, using mean (standard deviation [SD]) or median ([Q1/Q3]) for continuous variables and n, % and 95% confidence limits for categorical variables.ResultsOverall, 1981 pts were enrolled in this study, of whom 461 (23.3%) had a PsA diagnosis and received either anti-IL-17A (n=227; 49.2%) or other biologics (n=234; 50.8%). This subset of pts had a mean age of 48.7 yrs and a median disease duration of 18.9 yrs for PsO and 5.6 yrs for PsA (Table 1).Table 1.Baseline characteristics for PsO patients with PsA. Mean (SD) reported for all available data for that measure, unless stated otherwise.Overall (n=461)Anti-IL-17A (n=227)Other Biologics (n=234)Age, yrs48.7 (12.9)50.9 (12.9)46.6 (12.6)Male, n (%)232 (50.3)112 (49.3)120 (51.3)BMI (kg/m2)29.7 (6.2)29.8 (5.9)29.6 (6.4)Smoking status – Current, n (%)100 (25.4)41 (21.1)59 (29.5)Disease duration (PsA), yrs, median (Q1/Q3)5.6(2.2/13.1)5.6(2.0 / 13.8)5.5(2.3 / 12.8)Disease duration (PsO), yrs, median (Q1/Q3)18.9(9.7 / 28.6)18.9(9.2 / 30.3)18.7(10.1 / 27.3)Any previous biologic therapy, n (%)249 (54.0)123 (54.2)126 (53.8)PASI14.3 (9.3)13.6 (8.1)15.0 (10.3)BSA, %21.7 (19.4)19.8 (17.3)23.5 (21.1)mNAPSI16.6 (22.8)16.5 (25.5)16.7 (20.1)Presence of nail PsO, n (%)217 (47.2)103 (45.4)114 (48.9)PatGA3.5 (1.2)3.5 (1.3)3.6 (1.2)DLQI13.6 (7.9)13.4 (7.8)13.7 (8.0)HADS Depression score >10, n (%)73 (19.3)38 (20.5)35 (18.1)HADS Anxiety score >10, n (%)124 (32.8)62 (33.5)62 (32.1)BMI = Body Mass Index; BSA = Body Surface Area; DLQI = Dermatology Life Quality Index; HADS = Hospital Anxiety and Depression Scale; HADS >10 indicates significant symptoms of depression/anxiety; mNAPSI = Modified Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; PatGA = Patient Global Assessment of Disease Severity; Q1/Q3 = Quartile 1/3.At W12, 62.4% and 42.6% of anti-IL-17A-treated pts achieved PASI90 and PASI100, respectively, compared with 34.2% and 16.8% in the other biologics cohort, respectively (Figure 1). BSA <3% was reached by 70.9% of anti-IL-17A-treated pts and 49.5% in the other biologics cohort, while 71.2% and 44.8%, respectively, reached PatGA 0/1. Among pts with baseline DLQI ≥2, 38.0% and 27.1% of the anti-IL-17A and other biologics cohorts, respectively, reached DLQI 0/1.Figure 1.Percentage of patients receiving anti-IL-17A or other biologics who achieved PASI75/90/100, absolute PASI ≤1, BSA <3%, PatGA 0/1 and DLQI 0/1 (baseline DLQI ≥2) at Week 12. Bars represent upper 95% confidence limits.ConclusionThe effectiveness of blocking IL-17A on skin manifestations and on quality-of-life improvements in pts with PsO and PsA in the real-world study was consistent with observations from clinical trials.References[1]Zabotti A, et al. RMD Open 2019;5: e001067Disclosure of InterestsLars Erik Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals., Consultant of: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals., Grant/research support from: IIT research grants from Pfizer, AbbVie, UCB, Gilead, Biogen, Novartis, Eli Lilly, and Janssen pharmaceuticals., Frank Behrens Speakers bureau: Amgen, AbbVie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Eli Lilly, Boehringer and Sandoz, Consultant of: Amgen, AbbVie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Eli Lilly, Boehringer and Sandoz, Grant/research support from: AbbVie, Pfizer, Roche, Chugai, GSK and Janssen, Luis Puig Speakers bureau: Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Consultant of: Abbvie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, JS BIOCAD, Leo-Pharma, Eli Lilly, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi, UCB, Grant/research support from: Abbvie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, Leo-Pharma, Eli Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Adam Reich Speakers bureau: Abbvie, Novartis, Janssen, Pfizer, Sandoz, Galderma, Eli Lilly, Consultant of: Abbvie, Novartis, Janssen, Pfizer, Sandoz, Galderma, Eli Lilly, Thorsten Holzkaemper Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Alan Brnabic Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Khai Ng Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christopher Schuster Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andreas Pinter Speakers bureau: AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, Boehringer-Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO-Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough and UCB Pharma, Consultant of: AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, Boehringer-Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO-Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough and UCB Pharma
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Bubujlica, Husnija. "MANAGEMENT OF ORGANIZATIONAL CHANGES IN THE CASE OF HEALTHY COMPETENCE FOR THE COMPANIES." Knowledge International Journal 26, no. 6 (March 18, 2019): 1605–10. http://dx.doi.org/10.35120/kij26061605b.
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Although the company previously existed with the same purpose as today, only the business environment in which businesses operate are extremely changed. The globalization of business and progress in technological development have led to the emergence of turbulent business environment that companies impose new trends and measures of success.Although the changes in the organization of the company has always been present, the number and type of changes have greatly increased imposing new challenges to the successful management of the organization of the company. While it used to run the organization was an exception, now it has become the norm.Every company needs in its daily operations include strategic and active monitoring of the environment and change management in order to build a sustainable competitive ability, long-term growth and survival.Given that changes can and should be managed if the company wants to be competitive, through this mastarer paper presents the basic principles and principles of organizational changes, their effect on the entire organization, or the performance of individuals. It also points to the factor's that lead to changing the organization of those companies, as well as the stage of its growth, development and long-term survival, their impact in building sustainable competitiveness of the company.
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Febriana, Widia, Juliana Palit, and Defel Septia Septian. "SUPPLY CHAIN MANAGEMENT IN FINNISH RETAILING COMPARISON TO WORLD CLASS COMPANY CASE SEVEN ELEVEN JAPAN.CO AND WALMART." JCOMENT (Journal of Community Empowerment) 1, no. 3 (October 24, 2020): 22–39. http://dx.doi.org/10.55314/jcoment.v1i3.254.
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Lee titled The Triple A Supply Chain. In the article Lee picks up one world-class company that has excelled in designing its supply chain to meet the three points that make supply chains effective according to Lee. Those three are the long and short time flexibility and interest group commitment. The purpose of this research was to find out how the supply chains of Japanese and Finnish retail companies are different or similar to each other, how can Finnish retail companies improve their supply chains, and what kind of electronic tools are used in retail supply chains. The scope of the study was limited to the supply chains of grocery retail business in Finland and Japan and in particular Seven Eleven Japan and Walmart. The current situation of the grocery retail industry in Finland and Japan and the main trends of the grocery retail markets in both countries were described. Seven-Eleven Japan has developed an extensive franchise network and performs a key role in the daily operations of this network.
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Isaac, Renata, Diego De Melo Conti, Carlos Nabil Ghobril, Luiz Fostinone Netto, and Caludio Tucci Junior. "Sustainability and Competitive Advantage: A Study in a Brazilian Cosmetic Company." International Business Research 10, no. 1 (December 16, 2016): 96. http://dx.doi.org/10.5539/ibr.v10n1p96.
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Sustainability is an increasingly common and important issue in daily life, which in turn becomes an advantage when handled strategically by managers in their businesses. Nevertheless, in the Brazilian cosmetics and personal care industry one can find companies that consciously resist this trend. In this context, this article aims to highlight the advantages of using sustainability as a business strategy. The method used was a case study with a qualitative approach. In the case of the company, which was the subject of study of this work, the reasons that have led it to remain inert are strongly related to its model for running the business, especially the lack of long-term planning, a strong hierarchy, low leadership awareness and overvaluation of investors, making sustainability a seemingly incompatible matter for the organization. The studied company's own stakeholders, particularly employees, have identified several innovative opportunities for it to progress toward sustainability. However, in most cases, managers have been prevented from pursuing sustainable actions on the grounds that such initiatives are subjective and have no value.
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Melisa Anggraini, Wulandari, Bonaventura Hendrawan Maranata, and Febe Tri Sinta Dewi. "PENGARUH RASIO PERTUMBUHAN PREMI DAN RASIO BEBAN KLAIM TERHADAP TINGKAT KESEHATAN PERUSAHAAN ASURANSI DI MASA PANDEMI COVID-19." Applied Research in Management and Business 2, no. 1 (July 29, 2022): 1–8. http://dx.doi.org/10.53416/arimbi.v2i1.76.
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Pandemic of Covid-19 makes people increase the awareness of insurance in their daily lives. This increase in awareness has led to the importance of insurance companies that have a good level of health and their performance can be assessed by the public. Performance in insurance companies can be reflected in a system called the Early Warning System. Meanwhile, the health level of the insurance company is reflected in Risk Based Capital. The Early Warning System consists of several ratios, including the premium growth ratio and claim expense ratio This study aims to test whether the premium growth ratio and claim expense ratio affect the health level of the insurance company. The health level of the insurance company is proxied with Risk Based Capital (RBC). The population used in this study were insurance companies listed on the Indonesia Stock Exchange from the 2020-2021 period. The sample selection method used is purposive sampling. The hypothesis testing of the research used is multiple regression analysis using the eviews program. The result of this study is that there is no influence between the premium growth ratio and the health level of the insurance company and there is an influence between the claim expenses ratio and the health level of the insurance company.
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Ota, O. U., O. O. Obiukwu, B. E. Okafor, and D. A. Ekpechi. "Lean Optimization of Batch Production in an Aluminium Company." Asian Journal of Current Research 8, no. 4 (November 25, 2023): 62–81. http://dx.doi.org/10.56557/ajocr/2023/v8i48445.
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This work investigates the optimization of a batch type of production and operational management in an aluminium company using a lean manufacturing system. The operation and production system of the case study company runs in various sectors, which led to waste in the system, hindering the company's ability to meet customer demand. Through operational data analysis and questionnaires, the team identified the types of waste generated by the case study company. Lean manufacturing techniques such as eight deadly wastes, Heijunka, takt time, 5S approach, quality tool management, value stream mapping, Kaizen, Kaban, Gemba, and top and bottom-level involvement were employed to manage the waste. The findings reveal defects in inventory, transportation, waiting times, and untapped ideas of employees, all of which significantly impact the company's performance. This allows for daily production of small batches of aluminium alloys (AA3001, AA3105, and AA3110) without issues, supported by the principle of pull production. Additionally, the application of Takt time results in a significant reduction of production time, leading to improved efficiency. The study also highlights the high interaction effect of transportation, defects, and inventory wastes on various production lines, such as the bogie fitting line paint line, and anti-intrusion. Among the lean manufacturing tools, Kaban, standard work, and 5S are identified as the most frequently used. The research findings provide valuable insights for manufacturing industry leaders to spot the performance gaps and enhance the application of lean manufacturing practices.
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BUKANTAITĖ, Simona, and Kazimieras JUZĖNAS. "Evaluation and Modelling of Production Processes Affected by Unmeasured Situations: Case Study of a Metal Processing Company." Mechanics 28, no. 2 (April 15, 2022): 152–58. http://dx.doi.org/10.5755/j02.mech.29285.
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As the unpredicted situations can occur anytime, the production should be prepared to maintain the same pace as always. The pandemic of 2019 prooved that proper production processes are vital. The case study was made in metal processing company to examine how the workflow has changed after the implementations of virus prevention rules. Welding operation of metal furniture leg was observed and calculations presented – 115 minutes are wasted due to additional daily tasks caused by prevention of the pandemic. The recomendations were described and 160 minutes could be saved in accordance to them. The robotisation of processes and DSS implementation were presented.
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Magonet, Jonathan. "Rabbi Henry G. Brandt." European Judaism 55, no. 2 (September 1, 2022): 158–63. http://dx.doi.org/10.3167/ej.2022.550213.
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Born Heinz Georg Brandt in Munich, at the age of eleven his family escaped from Germany in 1939 to England and later settled in Tel Aviv. He served as an officer in the Palmach during the War of Independence and became an officer in the navy. From 1951 he studied economics at Queens University in Belfast, then worked as a market analyst for the Ford Motor company in the UK, while doing volunteer work in the Ilford Jewish community. In 1957 he began rabbinic studies as one of the first students at the recently opened Leo Baeck College, obtaining rabbinic ordination in 1961. His first rabbinic post was in Leeds, following which he served an international community in Geneva, and in 1978 was the founding rabbi of the Liberal Jewish congregation ‘Or Chadash’ in Zurich and later served as the community rabbi in Gothenburg.
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Goggin, Joyce. "‘Everything is awesome’: The LEGO movie and the affective politics of security." Finance and Society 3, no. 2 (December 19, 2017): 143–58. http://dx.doi.org/10.2218/finsoc.v3i2.2574.
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Scholarship on the finance-security nexus has typically been concerned with ‘first order’ phenomena, such as the interpenetration of the finance and security sectors. This article contributes to the debate by turning to an apparent epiphenomenon, namely The LEGO Movie, and using it to address some overlooked intersections between popular culture and the finance-security complex. The analysis first focuses on how finance and security are represented in the film, through the plot and the fictional company at the centre of the film’s conflict, to its LEGO minifigure characters and the playsets featured therein. The focus then shifts to how the LEGO Group’s business model informs the film in significant ways, from the plot’s motivation and structure, and the mise-en-scène, to how the film was produced. My argument throughout is that a seemingly innocent or insignificant film in fact participates in the financialization and securitization of daily life through its very style and status as a cultural product. Key here is how The LEGO Movie does this in ways that confound possible critique through the use of irony and cute aesthetics, as well as through its own supposed triviality.
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Cruz, Stephanie, and Celina Gómez. "Effects of Daily Light Integral on Compact Tomato Plants Grown for Indoor Gardening." Agronomy 12, no. 7 (July 19, 2022): 1704. http://dx.doi.org/10.3390/agronomy12071704.
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Our objective was to characterize the growth, physiological responses, fruit yield, and quality of tomato (Solanum lycopersicum L.) plants grown under different daily light integrals (DLIs) and photoperiods. In experiment I, nine compact tomato cultivars were grown indoors using broadband white light-emitting diode (LED) fixtures. Plants were grown under low (10.4 mol·m−2·d−1) and high (18.4 mol·m−2·d−1) DLIs with 12 and 16 h photoperiods, respectively, and two intermediate DLIs of 13.8 mol·m−2·d−1 with either 12 or 16 h photoperiods. In experiment II, three compact tomato cultivars were grown under the same low DLI with either 8 or 12 h photoperiods, and the same high DLI with either 12 or 16 h photoperiods. Generally, higher DLIs decreased plant growth and increased the fruit yield. Changing the DLI delivery strategy by adjusting the photoperiod and photosynthetic photon flux density (PPFD) did not have major effects on the growth, yield, and fruit quality of the compact tomato plants evaluated in this study, even though net photosynthesis increased under higher PPFDs in experiment II. Although several cultivars were affected by intumescence, only two cultivars showed treatment responses, for which the severity was generally higher in lower PPFDs using the same DLI.
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Ahmed M. Badeeb, Ahmed M. Badeeb. "An Application of Lean Manufacturing Techniques in Paint Manufacturing Company: A Case Study." journal of King Abdulaziz University Engineering Sciences 28, no. 1 (February 2, 2017): 51–73. http://dx.doi.org/10.4197/eng.28-2.5.
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As a result of the recession in Saudi Arabia, the manufacturing companies start thinking to reduce the operational cost and increasing the productivity through lean manufacturing principles. This paper is focused on increasing the productivity of a paint manufacturing company through implementing some of the lean manufacturing techniques. First, Value stream mapping analysis carried on throughout the manufacturing process and the areas of improvements in the company has been identified using fishbone diagram. Second, Work Place Organization (5S), Single Minute Exchange of Dies (SMED), Work Standardization and Kanban are the lean manufacturing techniques selected to solve different problems facing the company in these areas of improvements. A systematic approach of each technique implemented to measure its effect on the company productivity. It is observed that, applying (5S) and (SMED) techniques in the filling process decreased the changeover time by 59% and increased the daily productivity. Pareto chart recommended using work standardization in the charging process led to reduce the defects batches by 57%. Kanban system eliminated the shortages of semi-finish product and increased the output of the pre-weighing batches by 57%. In addition, overtime hours reduced by 77% and waste handling reduced by 85% and 53% for the non-hazardous and hazardous waste respectively
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Dunshee, Diana R., Yumin Dai, Jessica C. Jang, Alberto Risueño, Danny V. Jeyaraju, Patrick Hagner, Wendy L. See, et al. "CC-486 Mechanism Imparted By Extended Exposure of Azacitidine Upregulates Myeloid Differentiation Markers and Induces Cell Death in AML Cells." Blood 136, Supplement 1 (November 5, 2020): 33–34. http://dx.doi.org/10.1182/blood-2020-137606.
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BACKGROUND: CC-486, a DNA hypomethylating agent and epigenetic modifier, is an oral formulation of azacitidine (AZA) that is administered at lower exposures for extended durations (300 mg/day [d] for 14 or 21d/28d cycle) compared with the injectable formulation of AZA, which is given in a high exposure, limited duration regimen of 75mg/m2 for 7d/28d cycle. AZA induces DNA damage and cytotoxicity, and promotes changes in gene expression leading to cellular differentiation. As DNA incorporation of AZA is S-phase-dependent, it has been hypothesized that extended dosing with CC-486 prolongs drug exposure and DNA incorporation to enhance epigenetic activity. The mechanism of action imparted by extended dosing schedules of CC-486 is not fully understood. In patients with myeloid malignancies, DNA hypomethylation in blood is sustained throughout the 28d Tx cycle with extended CC-486 dosing regimens (Laille, 2015; Garcia-Manero, 2016). To better understand the mechanism of CC-486, we assessed the kinetics of expression of myeloid markers of cellular differentiation and cytotoxicity with various AZA dosing schedules in in vitro and in vivo models of AML. METHODS: AML cell lines (AML-193, KG1a, and MV4-11) were treated in vitro with AZA (0.05 - 5 µM daily for 5d or 15d), and at cumulative concentrations of 1 or 3 µM administered once or fractionated over 2-5d to experimentally model CC-486 extended exposures: 1 µM cumulative dose (1 µM × 1d, 0.5 µM × 2d, 0.33 µM × 3d, 0.25 µM × 4d, or 0.2 µM × 5d); 3 µM cumulative dose (3 µM × 1d, 1.5 µM × 2d, 1 µM × 3d, 0.75 µM × 4d, or 0.6 µM × 5d). AZA- or vehicle-treated cells were analyzed by flow cytometry, DNA methylation (Illumina Infinium EPIC assay), and RNA-Seq. Temporal expression of CD11b was assessed as a surface marker of myeloid differentiation, and Annexin-V staining was used to determine the extent of apoptosis and cell death. In efficacy studies, mouse models of AML (syngeneic, cell line-derived xenografts) were treated intraperitoneally with AZA regimens at 1 mg/kg/d × 15d (extended) or 3 mg/kg/d x 5d. RESULTS: Tx of AML-193 cells with 0.05 - 5 µM daily AZA led to upregulation of markers of myeloid differentiation (including CD11b) at lower doses, and a dose-dependent increase in apoptosis up to 7d after Tx initiation. Following Tx with 1 µM AZA for 1d, maximal cellular differentiation (ie, CD11b expression) occurred at d3 in 30% of AML-193 cells; conversely, cells treated with 0.2 µM/d AZA for 5d showed greater differentiation (40%) peaking on d7 (Fig A). CD11b expression was increased upon each subsequent cell division; after 5 cell divisions, CD11b upregulation was 4-fold higher in cells treated with multiple, lower AZA doses than with 1 µM AZA administered for 1d (Fig B). CD11b upregulation was not observed in the absence of cell division under serum starvation conditions for 3d (to induce cell cycle arrest), further suggesting that cell division is a requirement for AZA-induced CD11b changes (Fig C). Similarly, AML-193 cells treated with a 3 µM cumulative AZA dose over 1, 2, 3, 4, or 5d showed greater changes in myeloid differentiation marker expression, with peak apoptosis at d7 with extended dosing regimens (Fig D). In KG1a and MV4-11 cells, Tx with 1 µM AZA QD for 5d led to induction of myeloid differentiation by d7, and cell death (followed by recovery of undifferentiated cells) by d28. In contrast, daily Tx with 0.3 µM AZA for 15d led to slower, more robust upregulation of differentiation markers, peaking at d21 and accompanied by a gradual loss of cell viability. Extended AZA exposure to cells led to pronounced changes in gene expression (Fig E) and DNA methylation (Fig F) at both d7 (immune response gene signature) and d28 (cell adhesion gene signature) compared with limited duration exposure AZA. In mice, low exposure, extended regimens of AZA exhibited higher DNA and RNA incorporation into peripheral blood mononuclear cells (PBMCs) and bone marrow cells when compared with higher exposure, limited duration regimens. Extended AZA dosing led to significant efficacy in murine AML models. CONCLUSIONS: In AML cell lines, low exposure, extended duration AZA schedules modeling CC-486 induced robust changes in differentiation. These results suggest that CC-486-mediated effects using extended exposure regimens preferentially promote a differentiation effect and cell death of AML tumor cells. These mechanistic insights may help inform rational CC-486 combination Tx strategies. Disclosures Dunshee: Bristol Myers Squibb: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Genentech Inc.: Current Employment, Current equity holder in publicly-traded company. Dai:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Jang:Bristol Myers Squibb: Ended employment in the past 24 months. Risueño:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: Named in BMS (before Celgene) patent filings related to predictive patient response biomarkers in hematological malignancies. Jeyaraju:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Hagner:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. See:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. MacBeth:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Wang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. La Torre:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Skikne:Bristol Myers Squibb: Current Employment. Beach:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Kumar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Thakurta:Oxford University: Other: visiting professor; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Lopes de Menezes:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.
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Merola, J. F., L. E. Kristensen, F. Yang, S. Peterson, R. Teneralli, N. Massey, S. D. Chakravarty, et al. "POS1099 QUALITY OF LIFE, WORK IMPAIRMENT, AND DAILY ACTIVITY IMPAIRMENT OF PATIENTS WITH PSORIASIS VERSUS PSORIATIC ARTHRITIS: A REAL-WORLD SURVEY IN US AND EUROPE." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 877–78. http://dx.doi.org/10.1136/annrheumdis-2022-eular.4752.
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BackgroundPsoriasis (PsO) and psoriatic arthritis (PsA) and are chronic immune-mediated diseases characterised by joint inflammation and skin lesions which negatively impact patients’ health-related quality of life (HRQoL). Several previous comparative studies have focused on PsA patients with or without skin involvement. Better understanding of the impact of both PsO and PsA on HRQoL and work / activity impairment will improve understanding of the incremental burden of PsA compared to PsO, and may lead to more personalised treatment options.ObjectivesTo compare HRQoL, work impairment, and daily activity impairment of patients with a PsO diagnosis (dx) only, PsO dx with musculoskeletal (MSK) symptoms (sx), PsA dx with active skin sx, and PsA dx without active skin sx.MethodsData were drawn from the Adelphi PsO & PsA Disease Specific Programmes™ (DSP), real-world point-in-time surveys of rheumatologists, dermatologists and their consulting patients in the United States and Europe (France, Germany, Italy, Spain and UK); conducted in 2018/19. Patients were grouped according to their symptoms and confirmed diagnoses, comprising four groups:1. Patients with PsO dx only,2. Patients with PsO dx and with MSK sx,3. Patients with PsA dx and with active skin sx,4. Patients with PsA dx with no active skin sx,Multivariate linear regression analyses with marginal mean predictions examined differences in patient-reported outcome measures (PROMs) between the four groups. Measures included HRQoL (EuroQol 5-Dimension 5-Level [EQ-5D Utility] and EuroQoL Visual Analogue Scale [EQ-VAS]), work impairment, and daily activity impairment (Work Productivity and Activity Impairment Questionnaire [WPAI]). Analyses controlled for demographics (age, sex, BMI), comorbidities present in >10% of patients and current treatment class (biologics, csDMARDs, steroids & other).Results4491 patients were included: Group 1 (n=1833), Group 2 (n=91), Group 3 (n=2451), and Group 4 (n=116). 54% of patients were male, 89% of patients were white, with a mean age of 46.6 years. Demographics were consistent across all patient groups.The model-predicted EQ-5D-Utility was lower in Groups 2, 3 and 4, compared with Group 1 (p=0.003, p<0.001 and p=0.004 respectively). Similarly, predicted EQ-VAS was lower in Group 3 compared with Group 1 (p=0.006), Table 1.Table 1.Predictions of PROMs for PsO-PsA patient groupsPRO toolGroup [n]*Predicted PRO valuePopulation norm (MCID)Regression model p-value (vs. reference group)EQ-5D Utility score (n=1839)1 (ref) [743]0.9220.88 (0.07)2 [32]0.8160.0033 [1023]0.810<0.0014 [41]0.8500.004EQ-VAS (n=1882)1 (ref) [763]78.7878.2 (n/a)2 [36]70.560.0573 [1040]73.890.0064 [43]75.230.248WPAI % overall work impairment (n=1015)1 (ref) [422]15.36n/a (15.0)2 [14]17.860.5603 [558]22.16<0.0014 [21]26.090.014WPAI % work time missed (n=1028)1 (ref) [424]0.91n/a (n/a)2 [14]3.570.4863 [569]4.460.0024 [21]10.430.003WPAI % impairment while working (n=1153)1 (ref) [486]14.90n/a (20.0)2 [18]13.890.8463 [626]19.63<0.0014 [23]17.390.435WPAI % activity impairment (n=1818)1 (ref) [732]18.02n/a (20.0)2 [32]26.250.1223 [1012]26.14<0.0014 [42]25.240.044*n values provided for reference, but margins are predictions as a result of the model and not for the specific number of patients in each subgroup.(1) patients with PsO dx only(2) Patients with PsO dx and MSK sx(3) Patients with PsA dx and with active skin sx(4) Patients with PsA dx with no active skin sxOverall work impairment increased in Groups 3 and 4, compared with Group 1 (p<0.001 and p=0.014 respectively). Furthermore, Groups 3 and 4 missed more work compared with Group 1 (p=0.002 and p=0.003 respectively). Group 3 patients exhibited an increase in presenteeism and activity impairment compared with Group 1 (p<0.001), Table 1.ConclusionPatients experiencing PsA dx or MSK sx experienced an additional disease burden compared to patients with PsO sx alone, as measured by worse HRQoL and work impairment.Disclosure of InterestsJoseph F. Merola Consultant of: Merck Research Laboratories, Abbvie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GSK, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma, Lars Erik Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals, Consultant of: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals, Grant/research support from: Novo, UCB, Eli Lilly; Novartis and Abbvie, Feifei Yang Employee of: Employee of Janssen Pharmaceuticals, Steve Peterson Employee of: Employee of Janssen Pharmaceuticals, Rachel Teneralli Employee of: Employee of Janssen Pharmaceuticals, Nicola Massey Employee of: Adelphi Real World, Soumya D. Chakravarty Employee of: Employee of Janssen Pharmaceuticals, Megan Hughes Employee of: Adelphi Real World, May Shawi Employee of: Employee of Janssen Pharmaceuticals, Sarah Weatherby Employee of: Adelphi Real World, Christine Contre Employee of: Employee of Janssen Pharmaceuticals, Iris Lin Employee of: Employee of Janssen Pharmaceuticals, Fareen Hassan Employee of: Employee of Janssen Pharmaceuticals, M Elaine Husni Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Janssen, UCB, Pfizer, Regeneron, and BMS
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Zheng, Ying, Mi Mi Wang, Hui Qin Chen, Li Wei Huang, and Li Zhen Zhang. "Design and Realization of Wireless Lighting Control Based on ZigBee." Advanced Materials Research 1049-1050 (October 2014): 957–60. http://dx.doi.org/10.4028/www.scientific.net/amr.1049-1050.957.
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The low utilization rate of the traditional lighting system lighting and the overall layout and wiring costs high affecting the overall appearance and so many problems. This design of an intelligent lighting control system based on ZigBee technology. Using ZigBee CC2530 of the TI Company, the system researches and designs a sending module and a receiving module of intelligent wireless lighting control system. The ZigBee terminal node sends control signal to the coordinator node. The coordinator node CC2530 output of PWM wave signal according to the control instruction signal. the output of the PWM wave signal controlled the LED brightness through PT4115 chip LED driver circuit. Through tests,the results show that it can meet the demand of daily light regulation.
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Mease, P. J., P. Foley, K. Reich, J. Bagel, M. Lebwohl, Y. W. Yang, M. Shawi, et al. "POS1031 LOW INCIDENCE OF GASTROINTESTINAL-RELATED AND OVERALL SERIOUS ADVERSE EVENTS AMONG GUSELKUMAB-TREATED PATIENTS: POOLED ANALYSES OF VOYAGE 1 & 2 AND DISCOVER 1 & 2 THROUGH 1-YEAR." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 787–88. http://dx.doi.org/10.1136/annrheumdis-2021-eular.558.
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Background:Guselkumab (GUS), a human monoclonal antibody that specifically binds to the p19-subunit of interleukin (IL)-23, demonstrated efficacy in the Phase 3 VOYAGE 1&2 trials of patients (pts) with moderate to severe plaque psoriasis (PsO)1,2 and in the DISCOVER 1&2 trials of pts with active psoriatic arthritis (PsA).3,4 IL-17 inhibitors used to treat PsO and PsA have been associated with exacerbation or new onset of inflammatory bowel disease (IBD) (e.g., Crohn’s disease or ulcerative colitis).5Objectives:Evaluate the incidence of gastrointestinal (GI)-related and overall serious adverse events (SAEs) from pooled safety data through 1-year of GUS 100 mg treatment from the VOYAGE 1&2 and DISCOVER 1&2 trials.Methods:Using pooled safety data from the VOYAGE 1&2 PsO trials and DISCOVER 1&2 PsA trials, SAEs related to GI disorders were identified using the Medical Dictionary for Regulatory Activities (MedDRA) system-organ class “GI disorders”. Pts with a previous history of IBD were not excluded in these trials; medical history of IBD was collected at baseline in DISCOVER 1&2. Rates of overall SAEs and GI-related SAEs were calculated as the number of SAEs per 100 pt-years (PY) of follow-up (95% confidence intervals). Data are presented for the placebo (PBO)-controlled period (Weeks 0-16 for VOYAGE 1&2; Weeks 0-24 for DISCOVER 1&2) and through 1-year (defined as through Week 48 for VOYAGE 1&2; through Week 60 for DISCOVER 1, and through Week 52 for DISCOVER 2). Events of uveitis and opportunistic infections were also analyzed.Results:Through the PBO-controlled period, the overall rates of GI-related SAEs per 100 PY for pooled VOYAGE 1&2 were: PBO 0.78 (0.02, 4.34), GUS q8w 0; and for pooled DISCOVER 1&2: PBO 0.58 (0.01, 3.23), GUS q8w 0.58 (0.01, 3.21), GUS q4w 0. The GI-related SAEs included: gastrointestinal hemorrhage (PBO; n=1) for pooled VOYAGE 1&2; and inflammatory bowel disease (PBO; n=1) and mechanical ileus (GUS q8w; n=1) for pooled DISCOVER 1&2. Through 1-year, the overall rates of GI-related SAEs for pooled VOYAGE 1&2 were: Combined GUS group (GUS q8w and PBO→GUS groups) 0.51 (0.17, 1.20); and for pooled DISCOVER 1&2: GUS q8w 0.52 (0.06, 1.88), GUS q4w 0, Combined GUS group (GUS q8w, GUS q4w, and PBO→GUS groups) 0.21 (0.02, 0.74). The GI-related SAEs in the Combined GUS group for pooled VOYAGE 1&2 included: gastritis, hemorrhoids, inguinal hernia, pancreatitis, and umbilical hernia (0.10/100PY [0.00, 0.57]; n=1 for each); and in the Combined GUS group for pooled DISCOVER 1&2: mechanical ileus and pancreatitis chronic (0.10/100PY [0.00, 0.57]; n=1 for each). Overall, no cases of exacerbation or new onset of IBD were reported in GUS-treated pts, including 2 pts with a prior history of IBD in DISCOVER 1&2 (total PY of follow-up for the Combined GUS groups in VOYAGE and DISCOVER were 974 and 973, respectively). Through the PBO-controlled period, rates of overall SAEs for GUS-treated pts were comparable to PBO-pts and SAE rates remained low through 1-year of follow-up in the VOYAGE 1&2 and DISCOVER 1&2 trials. There were no reported cases of uveitis, opportunistic infections, or tuberculosis in GUS-treated pts through 1-year.Conclusion:Through 1-year of follow-up with GUS treatment in pooled VOYAGE 1&2 and DISCOVER 1&2, GI-related SAE rates were low. There were no reported cases of uveitis, opportunistic infections, or new onset/exacerbation of IBD in GUS-treated pts. No new safety concerns were identified through 1-year.References:[1]Blauvelt A., et al. J Am Acad Dermatol. 2017;76:405-17.[2]Reich K., et al. J Am Acad Dermatol. 2017;76:418-31.[3]Deodhar A., et al. Lancet. 2020;395:1115-25.[4]Mease P.J., et al. Lancet. 2020; 395:1126-36.[5]Hohenberger M., et al. J Dermatolog Treat. 2018;29:13-8.Disclosure of Interests:Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Peter Foley Speakers bureau: AbbVie, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Valeant, Galderma, GSK, Leo Pharma, and Roche, Consultant of: Janssen, Lilly, Novartis, Pfizer, Galderma, AbbVie, Amgen, AstraZeneca, Arcutis, Aslan, Boehringer Ingelheim, Celgene, Hexima, Merck, Sun Pharma, UCB Pharma, Valeant, BMS, Celtaxsys, CSL, Cutanea, Dermira, Genentech, GSK, Leo Pharma, Regeneron Pharmaceuticals Inc, Reistone, Roche, and Sanofi, Grant/research support from: AbbVie, Amgen, Celgene, Janssen, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; travel grants from AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer, Galderma, Leo Pharma, Roche, Sun Pharma, and Sanofi, Kristian Reich Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Jerry Bagel Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Janssen Biotech, and Novartis, Consultant of: AbbVie, Amgen, Celgene Corporation, Eli Lilly and Company, Janssen Biotech, Leo Pharma, Novartis, Sun Pharmaceutical Industries Ltd, and Valeant Pharmaceuticals, Grant/research support from: AbbVie, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Corrona, LLC, Dermavant Sciences, LTD, Dermira/UCB, Eli Lilly and Company, Glenmark Pharmaceuticals Ltd, Janssen Biotech, Kadmon Corporation, Leo Pharma, Lycera Corp, Menlo Therapeutics, Novartis, Pfizer, Regeneron Pharmaceuticals, Sun Pharma, Taro Pharmaceutical Industries Ltd, and Valeant Pharmaceuticals, Mark Lebwohl Consultant of: Aditum Bio, Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., BMD skincare, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Evommune, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Serono, Theravance, and Verrica, Grant/research support from: Abbvie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Evommune, Incyte, Janssen, Leo Pharmaceutucals, Ortho Dermatologics, Pfizer, and UCB, Ya-Wen Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Megan Miller Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Miwa Izutsu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yin You Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: Abbvie, Janssen, Pfizer, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Janssen, Leo, Lilly, Novartis, and UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Janssen, Leo, Lilly, Novartis, and UCB Pharma, Grant/research support from: Pfizer
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Zholkovsky, Alexander. "Digital High: The Art of Visual Seduction?" Arts 11, no. 5 (September 28, 2022): 97. http://dx.doi.org/10.3390/arts11050097.
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The paper focuses on the structure of an advertising image for a 2010s computer company in the neo-capitalist Moscow, Russia. The analysis looks back to the pioneering studies of advertising as a commercial “applied art” by Sergei Eisenstein, Leo Spitzer and Roland Barthes. The picture’s plot and composition are shown to be a consistent and sophisticated near-artistic design that uses textual puns, poetic topoi and visual stereotypes (in particular, sex appeal) for the promotion of the advertised merchandise (a smartphone). The psychological naturalization of the design is clarified with references to the insights of Sigmund Freud, Heinz Kohut and Gerard Genette into the dynamics of narcissism. In a widening circle, the contextualization of the design involves: the literary topos of using birds in love poetry (made famous by its treatment in the lyrics of the Roman poet Catullus) and in painterly variations on the theme; the narcissist discourse of a modern Russian poet (Eduard Limonov); and the grand pictorial tradition of portraying a nude (Venus) before the mirror (relevant classical canvases are considered briefly).
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Lonial, Sagar, Ravi Vij, Jean-Luc Harousseau, Thierry Facon, Philippe Moreau, Xavier Leleu, Amitabha Mazumder, et al. "Elotuzumab In Combination with Lenalidomide and Low-Dose Dexamethasone In Patients with Relapsed/Refractory Multiple Myeloma: Interim Results of a Phase 1 Study." Blood 116, no. 21 (November 19, 2010): 1936. http://dx.doi.org/10.1182/blood.v116.21.1936.1936.
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Abstract Abstract 1936 Background: Elotuzumab is a humanized monoclonal IgG1 antibody targeting CS1, which is highly and uniformly expressed on multiple myeloma (MM) cells, and important to myeloma cell survival. Elotuzumab exerts significant antitumor activity against primary myeloma cells via NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), regardless of sensitivity or resistance to conventional therapies. In preclinical studies, the activity of elotuzumab is independently enhanced by lenalidomide and dexamethasone. We present the results of an ongoing phase 1 study evaluating the maximum tolerated dose (MTD), safety, clinical response, and pharmacokinetics of elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed/refractory MM. Methods: Entry criteria included patients who had measurable disease, had experienced at least 1 relapse, and had not received lenalidomide for at least 6 weeks before the first dose of elotuzumab. The study enrolled 3 escalating dose cohorts of elotuzumab (5, 10, and 20 mg/kg IV), administered on days 1, 8, 15, and 22 of a 28-day cycle in the first 2 cycles, and then days 1 and 15 of each subsequent cycle, along with lenalidomide 25 mg PO daily on days 1 to 21 and dexamethasone 40 mg PO weekly. At each dose level, dose-limiting toxicities (DLTs) were assessed during cycle 1 and clinical responses were evaluated with International Myeloma Working Group (IMWG) criteria during each cycle. The first 5 patients received up to 6 cycles of therapy before a protocol amendment allowed subsequent patients to be treated until disease progression. Results: Twenty-nine patients with advanced MM (median stage III) who had received a median of 3 prior MM therapies, including bortezomib (69%), thalidomide (59%), or lenalidomide (21%), were enrolled. Of these, 28 received elotuzumab; 3 patients each were treated with 5 and 10 mg/kg and 22 with 20 mg/kg. Patients received a median of 8.5 treatment cycles and 20.5 doses of elotuzumab. Sixteen patients have permanently discontinued study treatment. No DLTs were observed up to 20 mg/kg during the escalation phase and hence no MTD was established. The most frequent grade 3/4 toxicities were neutropenia (36%) and thrombocytopenia (21%); 2 patients experienced 3 serious infusion-related reactions (1 patient with a grade 4 hypersensitivity reaction and 1 with 2 grade 3 stridor events) during the first treatment cycle. Objective responses (partial response or better) were obtained in 82% (23/28) of treated patients and 96% (21/22) of lenalidomide-naïve patients. ORRs were also high in patients who had received prior thalidomide 94% (15/16) or whose disease was refractory to the most recent therapy 82% (9/11). The median time to response was 7 weeks. The proportion of patients without disease progression (Kaplan-Meier estimate) at 16 months is 53% for total patients and 66% for patients in the 20 mg/kg elotuzumab cohort, who are being treated until disease progression. The median time to progression was not reached. Conclusions: The combination of elotuzumab, lenalidomide, and low-dose dexamethasone was generally well tolerated and showed encouraging overall response rates in patients with relapsed/refractory MM who had received multiple prior therapies. A larger phase 2 study is ongoing to confirm the rate and durability of the responses observed in this phase 1 trial. Disclosures: Lonial: Millennium, Celgene, Bristol-Myers Squibb, Novartis, Onyx: Advisory Board, Consultancy; Millennium, Celgene, Novartis, Onyx, Bristol-Myers Squibb: Research Funding. Vij:Bristol-Myers Squibb: Honoraria; Celgene: Research Funding; Celgene, Bristol-Myers Squibb: Speakers Bureau. Harousseau:Bristol-Myers Squibb, Celgene, Janssen-Cilag, Novartis, Onyx: Honoraria; Celgene, Janssen-Cilag: Speakers Bureau. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Moreau:Celgene, Facet Biotech, Bristol-Myers Squibb: Honoraria. Leleu:Janssen-Cilag, Celgene, Chugai Pharmaceutical, Roche, Amgen, Novartis, Leo Pharma: Consultancy, Honoraria, Research Funding. Kaufman:Celgene, Millennium: Consultancy; Celgene, Merck: Research Funding. Westland:Facet Biotech: Employment. Tsao:Facet Biotech: Employment. Singhal:Facet Biotech: Employment. Jagannath:Millennium, Takeda Pharmaceutical Company, Janssen-Cilag: Honoraria.
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VILLAREAL, BENITO, ARNEL MORTE, and JOSEPH PAÑA. "Artistic Value of Juan Luna’s Spoliarium." Scientia - The International Journal on the Liberal Arts 12, no. 1 (March 31, 2023): 62–69. http://dx.doi.org/10.57106/scientia.v12i1.139.
Full textAbstract:
This paper discussed the art appreciation technique using Jerrold Levinson’s artistic value in arriving at the importance of aesthetic experience in artwork. Levinson claimed that artistic value covers aesthetic value and achievement value, specifically in analyzing Juan Luna’s Spoliarium, which is considered the largest painting in the Philippines and is proclaimed as a national heritage. This paper argued that art should have aesthetic engagement from the viewer’s point of view which would lead them to discover its artistic value. Thus, this paper used the contextualizing technique since it augments and strengthens artistic engagement. References Adler, Mortimer. Six Great Ideas. New York: Macmillan Publishing Company, 1981.Descartes, Rene. The Philosophical Writings of Descartes (Volume II). Translated by John Cottingham, Robert, 1984.Goodman, Nelson. Languages of Arts. Indianapolis: The Bobbs-Merrill Company, Inc., 1968.Kant, Immanuel. Critique of Pure Reason. Translated by Norman Kemp Smith: Macmillan & Co., Ltd., 1929.Levison, Jerrold. Aesthetics and Ethics: Essays at the Intersection. Cambridge: Cambridge University Press, 1998._____________ Contemplating Art. Oxford: Oxford University Press, 2006._____________ Aesthetic Pursuits. United States of America: Oxford University Press, 2016.Luna, Juan. Spolarium. National Museum of the Philippines, 1884.Sporre, Dennis. Perceiving the Arts, 8th ed. United States of America: Prentice Hall, 2006.Stoothoff, and Dugald Murdoch. New York: Cambridge University Press.Tolstoy, Leo. What is Art? Translated by Richard Pevear & Larissa Volokhonsky. New York: Penguin Group, 1995.Wright, Susan. The Art, Young Children, and Learning. United States of America: Pearson Education Inc., 2003.www.flickr.com/photos/43184028@N02/440796048 29 June 2022.