Gotowa bibliografia na temat „Ltd Brickell Square Corporation”

Background:The 2019 update of the European League Against Rheumatism (EULAR) treatment recommendations strongly recommends co-administration of corticosteroids (CSs) with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with RA as bridging therapy to improve the success rate of the first-line treatment and to avoid disease flare-ups1; however, current treatment guidelines for RA in Japan do not clearly mention about their use. Poor disease management after the initial diagnosis can affect the overall use of health services and the economic burden on patients.Objectives:To describe medical costs and resource use in patients with early RA treated with and without oral or injectable corticosteroids (CSs) as part of their initial treatment with disease-modifying antirheumatic drugs (DMARDs) in Japan.Methods:We used a large Japanese administrative claims database constructed by the Japan Medical Data Center (JMDC)2. Patients with the International Classification of Diseases 10th revision (ICD-10) codes for RA were enrolled at the first DMARDs prescription after no DMARDs prescription period for 6-months (index date) in the period from 1/1/2012 to 12/31/2017. Patients who were observable for 12 months after the index date as a follow-up period were included. Patients treated with CSs within the follow-up period were compared with those without them (CS and non-CS group). The primary endpoint was mean medical cost per patient in the 12-month follow-up period. The secondary endpoints were costs for drugs, treatments, and materials and the proportions of patients using the subcategories of each resource. Drugs were divided into medications for RA or for comorbidities including adverse events (AEs). Costs in JPY were converted into EUR (1 EUR = 125 JPY in 2020).Results:Eligible patients of 1,670 and 1,487 were identified as the CS and non-CS group (median age: 51 years and 50 years). Total mean costs were significantly higher in the CS group (CS, 4,448 EUR, non-CS 3,208 EUR; P< 0.05). Drug, treatment, and material costs were significantly higher in the CS group than in the non-CS group (drug for RA and AEs, CS 2,367 EUR, non-CS 1,581 EUR, P < 0.05; drug for RA only, CS 2,265 EUR, non-CS 1,516 EUR, P < 0.05; treatment, CS 1,987 EUR, non-CS 1,562 EUR, P < 0.05; material, CS 94 EUR, non-CS 65 EUR; P < 0.05). The resource use in almost all drug subcategories were higher in the CS group (Table 1), as well as in all treatment and material subcategories.Table 1.Number and proportion of patients who used drugsType of drugDrug use, n (%)CS (N = 1,670)Non-CS (N = 1,487)P-valuecsDMARDsTotal1,635 (97.9)1,447 (97.3)0.328 Methotrexate1,481 (88.7)1,315 (88.4)0.870 Others790 (47.3)551 (37.1)< 0.001bDMARDsTotal342 (20.5)181 (12.2)< 0.001 TNFi252 (15.1)129 (8.7)< 0.001 IL6i93 (5.6)40 (2.7)< 0.001 T-cell40 (2.4)17 (1.1)0.012AnalgesicsTotal1,512 (90.5)1,274 (85.7)< 0.001 Acetaminophen379 (22.7)273 (18.4)0.003 Acetaminophen / Opioids84 (5.0)37 (2.5)< 0.001 NSAIDs1,459 (87.4)1,214 (81.6)< 0.001 Opioids16 (1.0)10 (0.7)0.491 Others198 (11.9)101 (6.8)< 0.001AntibioticsTotal1,086 (65.0)873 (58.7)< 0.001 Antibacterial drugs1,022 (61.2)800 (53.8)< 0.001 Antifungal drugs133 (8.0)86 (5.8)0.019 Antiviral drugs172 (10.3)129 (8.7)0.136 Antiparasitic drugs5 (0.3)8 (0.5)0.443Anti-osteoporotic drugs341 (20.4)95 (6.4)< 0.001bDMARDs=biological disease-modifying antirheumatic drugs; CSs=corticosteroids; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; IL6i=interleukin-6 inhibitor; NSAID=non-steroidal anti-inflammatory drug; T-cell=selective T-cell co-stimulation modulator; TNFi=tumor necrosis factor α inhibitor; P-values were calculated using Chi-square testConclusion:Patients with early RA treated with CSs in the first year after starting DMARDs tended to use more resources and have higher medical costs than patients not treated with CSs.References:[1]Smolen JS et al., Ann Rheum Dis. 2020;79(6):685-699.[2]JMDC claims database, Tokyo, Japan.Disclosure of Interests:Eiichi Tanaka Speakers bureau: AbbVie GK, Asahi Kasei Pharma Corporation, Astellas Pharma Inc, Ayumi Pharmaceutical Corporation, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Pfizer, Takeda Pharmaceutical Co., Ltd, and Teijin Pharma Ltd., Eisuke Inoue Speakers bureau: Pfizer Japan, Bristol-Myers Squibb K.K., Ryoko Sakai Speakers bureau: Bristol Myers Squibb Co., Ltd., Grant/research support from: Tokyo Women’s Medical University (TWMU), particularly the Division of Multidisciplinary Management of Rheumatic Diseases, Department of Rheumatology, has received unrestricted research grants from Ayumi Pharmaceutical Co.; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd., Nippon Kayaku Co., Ltd.; Taisho Toyama Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Co.; and Teijin Pharma Ltd., with which TWMU paid the salaries of RS., Iwasaki Katsuhiko: None declared, Ayako Shoji: None declared, masayoshi harigai Speakers bureau: AbbVie GK, Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Consultant of: AbbVie GK, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Gilead Sciences Inc., Grant/research support from: AbbVie GK, and Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd. Daiichi-Sankyo, Inc., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation., Nippon Kayaku Co., Ltd., Taisho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.

Abstract Background: CD56 expression is reported to be associated with adverse prognosis in patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy (Murray et al, 1999, Ferrara et al, 2000, Montesinos et al, 2011, Ono T et al, 2014). However, the prognostic significance of CD56 has not been elucidated, particularly when more potent agents are used. We recently reported long term analysis of the Japan Adult Leukemia Study Group (JALSG) APL204 study and concluded that maintenance therapy with tamibarotene was more effective than ATRA by reducing relapse in APL patients (Takeshita et al, 2018). In this study, the clinical significance of CD56 was evaluated with other surface markers on APL cells. Patients and Methods: Newly diagnosed APL patients with documented cytogenetic and/or molecular evidence of t(15;17)/PML-RARA were registered to the APL204 study from April 2004 to December 2010. The eligibility criteria included age between 15 and 70 years, ECOG performance status between 0 and 3, and sufficient function of organs. Induction therapy was composed of ATRA and chemotherapy whose dose and duration were based on initial white blood cell (WBC) count. Patients who achieved molecular remission after three courses of consolidation therapy were randomly assigned to maintenance therapy with tamibarotene 6 mg/day for 14 days or ATRA 45 mg/day for 14 days, which was repeated every 3 months for 2 years. The primary endpoint was hematological or molecular relapse-free survival (RFS). Surface markers, including CD56, were defined as positive if more than 10% of the CD45-gated cells expressed a specific antigen. Clinical characteristics were compared by the chi-square test or the Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous data. RFS, overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method, and compared using the log-rank test. Cumulative incidence of relapse (CIR) was compared by Gray's test. Multivariate analyses were also performed by the Cox-proportional-hazards-model. Clinical outcomes were renewed between January 2016 and June 2017 and the median follow-up period was 7.3 years. This study is registered at the University Hospital Medical Information Network Clinical Trials Registry as C000000154. Results: Of the 344 eligible patients, 319 (93%) achieved CR. After completing consolidation chemotherapy, 269 patients underwent maintenance random assignment; 135 to ATRA, and 134 to tamibarotene. Among 344 eligible patients, 325 were assessable for CD-phenotypes, and 45 (14%) were CD56-positive (CD56+). Among 269 patients who underwent the maintenance assignment, 34 (13%) were CD56+. CD56 expression was significantly associated with obvious bleeding (p<0.001). The CR rate and mortality during induction therapy were not significantly different compared with CD56- APL. RFS and CIR was significantly inferior in CD56+ APL (77% vs. 91%, HR 3.04, 95% CI 1.34-6.90, p=0.005 and 24% vs. 8%, p=0.004, respectively), whereas OS was not significantly different between the two groups 80% vs. 89%, p=0.069). In patients whose initial WBC counts were more than 3.0 x 109/L, RFS for the CD56+ group (n=14) was significantly inferior (64% vs. 87%, p=0.028), while in patients whose initial WBC count was under 3.0 x 109/L (n=20), RFS was not different (85% vs. 93%, p=0.164). Other surface markers such as CD13 and CD33 did not show any prognostic significance except for CD34 (p=0.040). By multivariate analysis, CD56 expression was an independent unfavourable prognostic factor for RFS (HR=3.19, 95% CI 1.40-7.25, p=0.006) together with more than 3.0 x 109/L WBC counts (p=0.001) and the ATRA arm in maintenance therapy (p=0.028). Conclusions: CD56 expression is an independent unfavorable prognostic factor for RFS in APL patients treated with ATRA and chemotherapy followed by ATRA or tamibarotene maintenance therapy, especially in patients whose initial WBC count was more than 3.0 x 109/L. The present study supports the prognostic significance of CD56 in the treatment of APL using more potent agents. Figure. Figure. Disclosures Takeshita: Chugai Pharmaceutical Co. Ltd.: Research Funding; Pfizer Japan Inc.: Research Funding; Astellas Pharma Inc.: Research Funding; Takeda Pharmaceutical Co. Ltd.: Research Funding; Bristol-Myers Squibb Co.: Research Funding; Kyowa Hakko Kirin Co. Ltd.: Research Funding. Asou:Asahi Kasei Pharma Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; SRL Inc.: Consultancy; Yakult Honsha Co., Ltd.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Astellas Pharma Inc.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding. Sawa:Celgene Corporation: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis International AG: Honoraria; CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria; Mundipharma K.K.: Honoraria. Dobashi:Celgene Co.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co. Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Pfizer Inc.: Research Funding; Sysmex Co.: Research Funding. Kobayashi:Pfizer: Research Funding; Ohtuka: Research Funding; Astellas: Research Funding. Kiyoi:Kyowa Hakko Kirin Co., Ltd.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Bristol-Myers Squibb: Honoraria; FUJIFILM Corporation: Research Funding; Celgene Corporation: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Sanofi K.K.: Research Funding; Astellas Pharma Inc.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Phizer Japan Inc.: Research Funding; Takeda Pharmaceutical Co., Ltd.: Research Funding; Novartis Pharma K.K.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding.

Abstract Background: Essential thrombocythemia (ET) is a subtype of chronic myeloproliferative neoplasms (MPN) characterized by thrombocytosis and disease-related symptoms, which may be difficult to manage. Patients with ET are also at higher risk of thrombosis and hemorrhage. Ideal therapeutic approaches should achieve adequate cytoreduction, reduce the risk of thrombo-hemorrhagic complications, and prevent progression to post-ET myelofibrosis (PET-MF) or secondary acute myeloid leukemia (AML). Low-dose aspirin with hydroxyurea (HU) is typically given as first-line therapy in high-risk patients. However, approximately 20-40% of ET patients become HU-intolerant or -resistant. In ET, resistance and/or intolerance portend an increased risk of thrombosis, hemorrhage, disease transformation and death. There is a paucity of prospective clinical trial data to guide management of ET patients who are HU resistant or intolerant. P1101 is a next generation monopegylated interferon (IFN) alfa-2b, developed specifically to treat MPNs, including ET. Study Design and Methods: The SURPASS-ET trial (NCT04285086) is a Phase 3, open-label, multicenter, randomized, active-controlled study to assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of P1101 after 12 months of treatment compared with anagrelide as second line therapy for subjects with ET who have shown resistance or intolerance to HU. The primary endpoint is durable modified ELN composite response at 9 and 12 months from dosing. Cochran-Mantel-Haenszel test will be used for comparing the primary endpoint in the two treatment arms. The PK parameters of P1101, including (but not limited to) C min, T max, C max, and area-under-curve (AUC) will be derived using PPK analysis and the relationship between exposure and efficacy and safety endpoints will be examined using E-R analysis. Evaluation of efficacy will include clinical laboratory assessments, allelic burden measurements of CALR, JAK2, and MPL, spleen size measurements, bone marrow sampling (optional), EQ-5D-3L, and MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) assessments. A total of 130 randomized subjects is planned to detect a difference of 40% (P1101) versus 15% (anagrelide) in durable ELN response rate with 90% power at alpha level = 0.05 using the chi-square test. To account for possible non-evaluability (e.g., no follow-up data), approximately 160 subjects will be randomized in this study to get 130 completed patients. Because of uncertainty in the assumptions on which the calculation of the sample size is based, an interim analysis for sample size adjustment will be implemented. Major inclusion criteria include subjects diagnosed with high-risk ET (either older than 60 years and JAK2V617F-positive at screening or having disease-related thrombosis or hemorrhage in the past), diagnosed according to the World Health Organization (WHO) 2016 criteria, documented resistance/intolerance to HU and IFN naïve or anti-P1101 binding antibody negative. Key exclusion criteria include pregnant females, significant cardiovascular disease, documented autoimmune disease and a history or presence of clinically significant depression or neurological disease. The study involves approximately 65 sites across the US, Taiwan, Japan, China, Hong Kong, Singapore, S. Korea, Canada, and Europe. To-date 55 patients (54 Asians, 1 Caucasian) have been randomized. The mean and median age at recruitment was 58.9 years (SD: 14.34) and 63 years (range 21 to 80 years) respectively. Twenty-seven men (49.1%) and twenty-eight women (50.9%) were recruited. Forty-two subjects (76.4%) had a TSS &lt; 20. The study is being overseen by a Data Safety Monitoring Board (DSMB). Figure 1 Figure 1. Disclosures Mesa: Gilead: Research Funding; Promedior: Research Funding; AOP: Consultancy; Incyte Corporation: Consultancy, Research Funding; Abbvie: Research Funding; Genentech: Research Funding; La Jolla Pharma: Consultancy; Novartis: Consultancy; Sierra Oncology: Consultancy, Research Funding; Samus: Research Funding; Pharma: Consultancy; CTI: Research Funding; Celgene: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; CTI: Research Funding. Komatsu: Fujifilm Wako Pure Chemical Corporation: Research Funding; Fuso Pharmaceutical Industries, Ltd.: Research Funding; Japan Tobacco Inc.: Consultancy; Otsuka Pharmaceutical Co. Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharma KK: Consultancy, Research Funding, Speakers Bureau; Shire Japan KK: Consultancy, Research Funding, Speakers Bureau; PharmaEssentia Japan KK: Consultancy, Current Employment, Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding. Sato: PharmaEssentia Japan KK: Current Employment. Qin: PharmaEssentia Corp.: Current Employment. Urbanski: PharmaEssentia Corporation: Current Employment. Shih: PharmaEssentia Corporation: Consultancy. Zagrijtschuk: PharmaEssentia U.S.A. Corp.: Current Employment. Zimmerman: PharmaEssentia Corporation: Current Employment. Verstovsek: Gilead: Research Funding; Protagonist Therapeutics: Research Funding; NS Pharma: Research Funding; Incyte Corporation: Consultancy, Research Funding; PharmaEssentia: Research Funding; Ital Pharma: Research Funding; CTI BioPharma: Research Funding; Blueprint Medicines Corp: Research Funding; AstraZeneca: Research Funding; Promedior: Research Funding; Genentech: Research Funding; Celgene: Consultancy, Research Funding; Roche: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy.

Introduction: Myelodysplastic syndromes (MDS) is thought to develop and progress as a result of accumulation of genetic mutations. This multicenter, open-label, phase II study examined impact of gene mutations on the effect of darbepoetin alfa (DA) for anemia. Death within 1 year and progression to acute myeloid leukemia (AML) were also examined. Methods: DA ≤240 μg was administered once weekly for 16 weeks to DA-naive, low-risk MDS (low or Intermediate-1 [Int-1] risk defined by the International Prognostic Scoring System [IPSS] risk classification) patients with anemia. DNA was extracted from the peripheral blood of patients, and presence of previously reported high-frequency gene mutations in MDS (SF3B1, TET2, SFRS2, ASXL1, DNMT3A, etc.) was analyzed by next-generation sequencing. Primary endpoint was association between frequently observed mutated genes and therapeutic effect of DA (IWG criteria 2006 (HIE)) at 16 weeks. A secondary endpoint was survival analysis results for death and progression to AML within one year after 16 weeks of treatment, with the date of first treatment as the starting date. For AML, progression to AML and subsequent death were stated as events, and the patients without confirmed progression to AML were censored at the date of last known survival. For overall survival, death from any cause was considered an event, and for the survival cases, the study was terminated at the date of last known survival. For the primary endpoint, relative risk and 95% confidence intervals (CI) were calculated using Wilson's score method; statistical significance was assessed using Pearson's chi-square test. Multivariate analysis was performed by adding baseline erythropoietin (EPO) levels (low: &lt;91.8, high: 91.8+ [mIU/mL]) to the explanatory variables, and odds ratio was calculated using logistic regression model. Survival curve was estimated using Kaplan-Meier method and median survival time (MST) was calculated using Brookmeyer and Crowley method. Results: Of the 85 patients enrolled between August 2016 and May 2019, 4 patients who were judged ineligible and 2 patients who discontinued the study prior to the start of treatment were excluded, and 79 subjects were included in the analysis (full analysis set). Of 79 subjects, 52 (65.8%) were male (median age 77.0 [29-90] years). IPSS risk was low in 27 (36.7%) and Int-1 in 50 (63.3%) subjects. The frequently mutated genes (³10%) were SF3B1 (24, 30.4%), TET2 (20, 25.3%), SRSF2 (10 cases, 12.7%), ASXL1 (9, 11.4%), and DNMT3A (8, 10.1%). Overall response rate was 70.9%. Univariate logistic regression analaysis did not show any significant association between these mutations and therapeutic efficacy of DA. The same results were obtained when the analysis was limited to red blood cell transfusion-dependent subjects (n=15). After adjusting against baseline EPO values, mutations of ASXL1 gene were associated with significantly worse response (odds ratio 0.180 [0.035-0.928], p = 0.040). Six (7.6%) confirmed cases of AML and 17 (21.5%) deaths (death before confirmed AML) were observed. Overall, 21 deaths were observed including 4 deaths after progression to AML. The median survival time (95% confidence interval) from the start of treatment to confirmed AML or death was 41.3 months (30.6 months - Not reached). Conclusions: The results of this exploratory study suggest that the presence of ASXL1 gene mutations may result in poor response to the anemic treatment with DA in low-risk MDS. The current analysis of progression to AML and death included subjects whose observation period did not reach the prespecified number of days. For such cases, the outcome research will be conducted around October 2020 and updated results will be presented at the ASH 2020 conference. Disclosures Ichikawa: Novartis, Takeda: Honoraria. Shibayama:Taiho: Research Funding; Shionogi: Research Funding; Ono: Honoraria, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Takeda: Honoraria, Research Funding; Merck Sharp & Dohme: Research Funding; Sumitomo Dainippon: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Kirin: Honoraria; Otsuka: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Fujimoto: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Teijin: Research Funding; Mundi Pharma: Honoraria. Maeda:Kyowa Kirin Co.Ltd.: Honoraria, Research Funding. Kawabata:Celgene Corporation: Consultancy; Celgene Corporation: Honoraria; Sanofi K. K: Honoraria; Novartis Pharma K. K.: Honoraria; Chugai Pharmaceutical Co., Ltd: Honoraria. Matsumura:Shionogi & Co., Ltd.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Kyowa Kirin Co., Ltd.: Research Funding; ONO PHARMACEUTICAL CO., LTD.: Research Funding; Eisai Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Janssen Pharmaceutical K.K: Speakers Bureau; Amgen K.K.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; Astellas Pharma Inc.: Speakers Bureau; DAIICHI SANKYO COMPANY, LIMITED.: Speakers Bureau; Pfizer Japan Inc.: Speakers Bureau; Novartis Pharma KK: Speakers Bureau; Bristol-Myers Squibb Company: Speakers Bureau. Ogawa:Eisai Co., Ltd.: Research Funding; KAN Research Institute, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chordia Therapeutics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Asahi Genomics Co., Ltd.: Current equity holder in private company; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding. Mitani:CHUGAI: Research Funding; Takeda: Research Funding; KYOWA KIRIN: Consultancy, Research Funding.

Background: Pretreatment status assessment at diagnosis in patients with chronic myeloid leukemia in chronic phase (CML-CP) is more important for successful treatment in the tyrosine kinase inhibitors (TKIs) era. For instance, the Charlson comorbidity index (CCI) score is considered the useful tool for predicting overall survival (OS) in patients with CML treated with imatinib (IM) (Saussele S et al., 2015). However, the effect of CCI in patients with CML treated with second-generation TKI (2nd TKI) and clinical practice setting was unknown. This study aimed to evaluate the effect of pretreatment statuses, including CCI, on OS of participants of the New TARGET observational study 1 conducted by the Japanese Society of Hematology (JSH). Methods: Patients newly diagnosed with CML-CP were registered to the New TARGET observational study 1 from April 2010 to March 2013. They were treated with TKIs (IM, nilotinib [NIL], or dasatinib [DAS]) after registration. Exclusion criteria were defined as follows: (1) accelerated phase/blast crisis (AP/BC) CML and (2) pretreatment with interferon-alfa, any TKIs, or hydroxyurea for more than 3 months, or allogeneic hematopoietic stem cell transplantation before registration. Other details of the protocol were previously reported (Kizaki et al., 2019). Patients were classified into CCI risk groups of 2, 3, and ≥4 for analysis. The New TARGET observational study 1 was supported by research fundings from Novartis Pharmaceuticals and Bristol-Myers Squibb to JSH. This subgroup analysis was approved by the institutional review board of the Hamamatsu University School of Medicine. The chi-square test was used to compare clinical characteristics for categoricaldata and the Wilcoxon rank-sum test for continuous data. OS was calculated using the Kaplan-Meier method and compared by the log-rank test. Gray's test was used to compare cumulative incidence curves. Cox proportional hazard analyses were performed to determine prognostic indicators of OS. The Wald test was used to assess the prognostic significance of a candidate variable. Statistical analyses were performed using EZR, a graphical user interface for R (Kanda Y, 2013). Results: Among 506 enrolled patients, 475 with a median age of 56 years were assessable. The median follow-up period was 5.4 years. In total, 103 patients (21.7%) had various types of comorbidities, with diabetes mellitus, mild liver disease, peripheral vascular disease, myocardial infarction, renal disease, and peptic ulcer disease (7.3%, 4.1%, 3.2%, 2.6%, 2.2%, and 2.2%, respectively) as the most common. The lowest CCI score was 2 owing to CML. CCI scores were stratified as follows: 2, 372 patients (78%); 3, 74 patients (16%); and ≥4, 29 patients (6%). Higher CCI scores were significantly associated with older age (P <.001). Overall, 151 patients were treated with IM, 175 with NIL, and 149 with DAS. Patients with higher CCI scores tended to be treated with IM. Differences in cumulative incidence of complete cytogenetic response, major molecular response, and AP/BC were not statistically significant in the observational period according to CCI scores (P = 0.46, P = 0.58, and P = 0.63, respectively). No differences in the treatment response among the CCI risk scores were found in the IM and 2nd TKI cohorts. The OS of patients with CCI scores of 2, 3, and ≥4 were 94.3%, 89.3%, and 73.9%, respectively (P <.001). Similar results for OS were observed in IM and 2nd TKI cohorts. In the multivariate analysis including the CCI, performance status (PS), the presence of additional chromosomal abnormalities (ACAs), EUTOS long-term survival score (ELTS), age (≥65 years), and the choice of initial TKI treatment (IM vs. 2nd TKIs), the CCI score of ≥4 and PS of ≥2 were identified as adverse prognostic factors for OS (Wald test, P <.01 and P = 0.02). Hazard ratios for the CCI score of ≥4 (vs. score 2) and PS of ≥2 (vs. PS 0) were 5.94 (95% confidence interval [CI]: 1.94-18.2; P <.01) and 6.01 (95% CI: 1.67-21.6; P <.01), respectively. ACAs, ELTS, and older age did not significantly affect OS in this cohort including patients treated with 2nd TKI. Conclusion: Our results demonstrated that comorbidities and poor PS at diagnosis were important predictive factors for OS, regardless of the type of TKI in patients with CML-CP. The risk-adopted management based on comorbidities and PS may be important to further improve the clinical outcomes of CML-CP. Disclosures ONO: Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Chugai Pharmaceutical Co.,Ltd.: Research Funding; Kyowa Hakko Kirin: Research Funding; ONO Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Merck Sharp & Dohme: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Pfizer: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria. Takahashi:Novartis Pharmaceuticals: Research Funding, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Ono Pharmaceutical: Research Funding; Bristol-Myers Squibb: Speakers Bureau; Otsuka Pharmaceutical: Research Funding, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Eisai Pharmaceuticals: Research Funding; Astellas Pharma: Research Funding; Asahi Kasei Pharma: Research Funding; Chug Pharmaceuticals: Research Funding. Kizaki:Kyowa Kirin: Research Funding; Chugai Pharm: Research Funding; Novartis: Speakers Bureau; Ono Pharm: Research Funding, Speakers Bureau; Takeda Pharm: Research Funding, Speakers Bureau; Janssen Pharm: Speakers Bureau; Sumitomo Dainippon Pharm: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Celgene: Speakers Bureau; Daiichi Sankyo: Research Funding. Kawaguchi:Alexion: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Suzuki:Merck Sharp & Dohme: Honoraria; Bristol-Myers Squibb: Honoraria; Chugai Pharmaceutical Co.,Ltd.: Honoraria; Eisai: Honoraria; Janssen: Honoraria; ONO Pharmaceutical Co., Ltd.: Honoraria; Celgene: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria; Meiji Seika: Honoraria; Kyowa Hakko Kirin: Honoraria; AbbVie: Honoraria; Novartis: Honoraria. Yamamoto:Pfizer: Honoraria; Sanofi: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Gilead Sciences: Research Funding; Otsuka: Honoraria; Novartis: Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Solasia Pharma: Research Funding; SymBio: Research Funding; MSD: Consultancy, Honoraria; Janssen: Honoraria; Sumitomo Dainippon: Honoraria; ARIAD: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Bayer: Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Ono: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; HUYA/IQVIA Services Japan: Consultancy, Honoraria; Incyte: Research Funding; Kyowa Kirin: Honoraria; Meiji Seika Pharma: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria, Research Funding. Matsumura:Otsuka Pharmaceutical: Consultancy, Research Funding; Novartis: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau.

Background:A number of previous reports suggested that obesity is one of the baseline factors indicates refractory to biologic disease-modifying antirheumatic drugs (bDMARDs). However, difference of the significant responses appears on obesity patients depending on each kind of drug is yet unclear. However, it is yet unclear how the significant responses on obesity patients vary on each kind of drug.Objectives:To assess whether obesity affects clinical outcome in rheumatoid arthritis (RA) treated with each molecular-targeted agent including bDMARDs and tofacitinib.Methods:In Kansai consortium for well-being of rheumatic disease patients (ANSWER) cohort, which was the real-world retrospective cohort of clinical database for rheumatic diseases, RA patients who initiated biological / targeted disease modifying anti-rheumatic drugs were included and consecutively followed. Obesity was defined as BMI over than 25, and patients were divided between obese (“Ob”) and non-obese (“non-Ob”) patients. SDAI (simplified disease activity index) was compared between non-Ob and Ob at month 0, 3, 6, 9, 12 after the indicated drugs were administered. Using logistic regression analysis, odds ratio (OR) and their corresponding 95% confidence intervals (95% CIs) were further calculated to estimate achievement rate of SDAI remission defined as lower than 3.3 by obesity and other relevant clinical parameters. Once after the drugs were discontinued by any unfavorable reason, disease activities were no more scored and the Last Observation Carried Forward (LOCF) imputation method was used for SDAI at month 3 and thereafter.Results:A total of 1936 patients met in the inclusion criteria were under the analysis. In each drug, SDAI remission rate (non-Ob, Ob, p-value by Chi-square test) at month 12 was as follows; Infliximab (IFX, n=135): 43%, 38%, NS (not significant); Etanercept (ETN, n=188): 44%, 19%, p=0.0122; Adalimumab (ADA, n=169): 50%, 56%, NS; Golimumab (GLM, n=315): 36%, 30%, NS; Certolizumab pegol (CZP, n=131): 33%, 56%, p=0.0287; Tocilizumab (TCZ, n=423): 41%, 29%, p=0.0456; Abatacept (ABT, n=144): 26%, 23%, NS; Tofacitinib (TOF, n=69): 27%, 23%, NS. In multivariate analysis to predict SDAI remission at month 12, obesity was an independent protective factor in CZP (OR: 0.29, 95% CIs: 0.10 – 0.83), but was an independent risk factor in TCZ (OR: 1.9, 95% CIs: 1.01 – 3.61) irrespective of age, sex, disease duration, SDAI at month 0 or number of previous bDMARDs. Any other drug including ETN did not show significant result between non -Ob and Ob in the multivariate analysis.Conclusion:Obese patients were more resistant to TCZ but more effective in CZP than non-obese patients.References:[1]Ann Rheum Dis. 2018;77(10):1405-1412. Joint Bone Spine. 2019;86(2):173-183.Disclosure of Interests:Kosaku Murakami Speakers bureau: AbbVie, Eisai, and Mitsubishi Tanabe Pharma., Motomu Hashimoto Grant/research support from: Bristol-Myers Squibb, Eisai, and Eli Lilly and Company., Speakers bureau: Bristol-Myers Squibb and Mitsubishi Tanabe Pharma., Koichi Murata Grant/research support from: KMurata belong to a department that has been financially supported by four pharmaceutical companies (Mitsubishi-Tanabe, Chugai, AYUMI and UCB Japan)., Employee of: KMurata belong to a department that has been financially supported by four pharmaceutical companies (Mitsubishi-Tanabe, Chugai, AYUMI and UCB Japan)., Speakers bureau: KMurak has received speaking fees, and/or consulting fees from Eisai Co. Ltd, Chugai Pharmaceutical Co. Ltd., Pfizer Japan Inc, Bristol-Myers Squibb, Mitsubishi-Tanabe Pharma Corporation, UCB, Daiichi Sankyo Co. Ltd. and Astellas Pharma Inc., Wataru Yamamoto: None declared, Ryota Hara Speakers bureau: RH received a speaker fee from AbbVie, Masaki Katayama: None declared, Akira Onishi Speakers bureau: AO received a speaker fee from Chugai, Ono Pharmaceutical, Eli Lilly, Mitsubishi-Tanabe, Asahi-Kasei, and Takeda, Kengo Akashi: None declared, Koji Nagai: None declared, Yonsu Son: None declared, Hideki Amuro: None declared, Toru Hirano Grant/research support from: TH received a research grant and/or speaker fee from Astellas, Chugai, Nippon Shinyaku, Abbvie, Eisai, and Ono Pharmaceutical, Speakers bureau: TH received a research grant and/or speaker fee from Astellas, Chugai, Nippon Shinyaku, Abbvie, Eisai, and Ono Pharmaceutical, Kosuke Ebina Grant/research support from: KE has received research grants from Abbie, Asahi-Kasei, Astellas, Chugai, Eisai, Ono Pharmaceutical, and UCB Japan., Employee of: KE is affiliated with the Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, which is supported by Taisho., Speakers bureau: KE has received payments for lectures from Abbie, Asahi-Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Sanofi, and UCB Japan., Kohei Nishitani Grant/research support from: KN belong to a department that has been financially supported by four pharmaceutical companies (Mitsubishi-Tanabe, Chugai, AYUMI and UCB Japan)., Masao Tanaka Grant/research support from: AbbVie, Asahi Kasei Pharma, Astellas Pharma, Ayumi Pharmaceutical, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Taisho Pharmaceutical, and UCB Japan., Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Novartis Pharma, Pfizer, Taisho Pharmaceutical, Takeda Pharmaceutical, and UCB Japan., Hiromu Ito: None declared, Koichiro Ohmura Grant/research support from: Astellas Pharma, AYUMI Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Japan Blood Products Organization, Mitsubishi Tanabe Pharma, Nippon Kayaku, Nippon Shinyaku, Sanofi, and Takeda Pharmaceutical., Speakers bureau: AbbVie, Actelion Pharmaceuticals Japan, Asahi Kasei Pharma, AYUMI Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Novartis Pharma, and Sanofi.

Abstract Background: Bendamustine and rituximab (BR) is a commonly chosen frontline treatment for grade 1-2 (G 1-2) follicular lymphoma (FL). This regimen resulted in significantly longer progression-free survival (PFS) and less toxicity compared to R-CHOP in the STiL trial [Rummel et al., 2013] and similar results were observed when comparing BR vs. R-CHOP/R-CVP in the confirmatory BRIGHT trial [Flinn et al., 2014, updated ASCO 2017]. Importantly, patients (pts) with grade 3A (G 3A) FL were excluded from these studies, yet the conclusions are often extrapolated to the treatment of G 3A pts. Notably, G 3A pts were included in the GALLIUM trial which used both bendamustine as well as CHOP backbones. Several retrospective studies of FL pts treated with frontline R-CHOP have demonstrated equivalent or improved overall survival (OS) for G 3A relative to G 1-2 FL (Koch et al., 2016, Mustafa et al., 2017, Yuan et al., 2017, Maeshima et al., 2013). Early disease progression after diagnosis and treatment with frontline R-CHOP has been identified as a strong predictor of poor OS in FL pts [Casulo et al. 2015], but has not been assessed in pts treated with frontline BR. We retrospectively evaluated outcomes of a large cohort of FL pts treated with frontline BR and stratified the results based on histologic grade and early vs. late progression. Methods: We reviewed medical records of adult (age >18) pts with FL treated with frontline BR at 18 US cancer centers. There was no central pathology review; each academic institution confirmed the diagnosis and grade of FL. Pts with unknown grade, grade 3B, or cutaneous FL were excluded. Baseline characteristics between grades were evaluated with the Chi-Square test for categorical variables and the Mann-Whitney U for continuous variables. Outcomes were calculated from time of initiation of BR. Patients were grouped according to whether or not they had progression of disease within 24 months of BR initiation (POD24). OS and PFS were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: 687 pts were included (616 G 1-2, 71 G 3A). Median age at diagnosis was 60 years (range 21-94) with 53% men. The median time from diagnosis to treatment with BR was 1 month (range 0-139). The median duration of follow up for the entire cohort was 39 months. Characteristics including age, gender, ethnicity, ECOG, stage, LDH, and FLIPI are shown in the Table, and did not significantly differ between G 1-2 and G 3A pts. Rates of complete response (CR) and partial response (PR) to BR were similar between G 1-2 and G 3A (72%/22% vs. 66%/21%, respectively, p=0.114) but progressive disease (PD) was higher in G 3A pts (11.9%) relative to G 1-2 (4.8%, p=0.025). As shown in the Figure (A and B), 3-year PFS and OS was significantly longer for G 1-2 vs. G 3A pts (75% vs. 65%, log rank p= 0.035 and 90% vs. 86%, log rank p=0.007, respectively). Seventy-six (12.3%) of the 616 G 1-2 pts and 13 (18.3%) of the 71 G 3A pts experienced POD24 (p=0.19). For pts with both G 1-2 and G 3A FL, POD24 was associated with inferior OS (3-year OS 95% vs. 57% for G 1-2 pts, log rank p<0.0001 and 3-year OS 93% vs. 37% for G 3A pts, log rank p<0.0001) compared to patients without POD24. Conclusions: G 3A FL pts have an inferior OS and are significantly more likely to have PD to frontline BR compared to G 1-2, which differs from the published experience with R-CHOP. Similar to outcomes after frontline treatment with R-CHOP, POD24 after frontline BR for FL is associated with very poor OS. Future studies are needed to address optimal frontline management of pts with G3A as well as for pts with any grade FL with POD24 after frontline BR. Disclosures Nastoupil: Novartis: Honoraria; Genentech: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; TG Therappeutics: Research Funding; Karus: Research Funding; Merck: Honoraria, Research Funding; Spectrum: Honoraria; Janssen: Research Funding; Juno: Honoraria. Cerhan:Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding; Nanostring: Research Funding. Maurer:Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Smith:Genentech: Research Funding; Incyte Corporation: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Merck Sharp and Dohme Corp.: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Seattle Genetics: Research Funding. Lossos:Affimed: Research Funding. Portell:TG therapeutics: Research Funding; Amgen: Consultancy; Kite: Research Funding; AbbVie: Research Funding; BeiGene: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Research Funding; Infinity: Research Funding. Calzada:Seattle Genetics: Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; BioInvent: Consultancy. Ghosh:Spectrum: Consultancy; SGN: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics, an Abbvie Company: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Honoraria, Research Funding; Celgene: Consultancy; Juno: Consultancy, Research Funding; Abbvie: Consultancy, Speakers Bureau; Genentech: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; PCYC: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Forty seven Inc: Research Funding. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Caimi:Kite Pharma: Other: Advisory Board Participation; Genentech: Other: Advisory Board PArticipation, Research Funding; Celgene: Speakers Bureau; Kite Pharma: Other: Advisory Board Participation. Danilov:Gilead Sciences: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; Astra Zeneca: Consultancy; Genentech: Consultancy, Research Funding; Takeda Oncology: Research Funding; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding. Martin:AstraZeneca: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy; Kite: Consultancy; Gilead: Consultancy; Bayer: Consultancy. Kamdar:Seattle Genetics: Speakers Bureau; Genentech: Consultancy. Kahl:AstraZeneca: Consultancy; Acerta: Consultancy; Juno: Consultancy; CTI: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy. Hill:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction & Objective: In the midst of the COVID-19 pandemic in 2020 and 2021, we reported a significant increase in homeostatic model assessment for insulin resistance (HOMA-IR) values among 14-15 years old students. In this study, we conducted prolonged surveys incorporating data until 2023. Methods: The study included 430 students aged 14-15 who underwent health examinations between 2015 and 2023 (236 males, 194 females). Using its data, HOMA-IR, BMI, and obesity levels were calculated, and temporal changes were assessed using the Kruskal-Wallis test. Insulin resistance (IR) is defined as HOMA-IR ≥2.5 and temporal changes were assessed using the Chi-square test. Results: A significant change in the median HOMA-IR was observed over the 8-year period (p &lt; 0.001). Conversely, no significant differences were observed in the median BMI and obesity levels over the 8-year period (p = 0.055, p = 0.064). Figure1 illustrated changes in the proportion of study participants with IR over time. Conclusion: The significant increase in HOMA-IR observed after 2020 significantly decreased to values similar to pre-COVID-19 levels by 2023. However, BMI and obesity levels showed no temporal changes. Our findings suggest that changes in lifestyle due to the COVID-19 pandemic may have influenced insulin resistance in 14-15 years old students, irrespective of obesity status during 2020-2022. Disclosure T. Ohno: None. M. Ishiguro: None. Y. Suganuma: None. R. Nishimura: Speaker's Bureau; Abbott. Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Medtronic, Sanofi, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Eli Lilly and Company, Novo Nordisk A/S. Consultant; Terumo Corporation. Funding Ministry of Education, Culture, Sports, Science, and Technology, Japan (Kiban [c] 23590815 and Kiban [c] 19590600)

This culture enables all employees to use their initiative, take risk, experiments, innovate and un-grade their potentialities to meet the existing and future challenges in short and long term perspectives. In this connection working conditions of employees within organization play a vital role for enhancing the economic productivity of an organization. At the national level, the dimension of HRD needs to be reviewed periodically and adjustments made according to the change in environment. India has one of the largest reservoirs of human resource in the World, which can combat any problem in the process of development especially at the economic level. The main objective of the study is to assess the levels of the utilization of human resources as well as to determine the functional status of the units. Keeping the above aspects under consideration, the study selected two large scale industrial units Viz., Hindustan Petroleum Corporation Ltd. and Coromandel Fertilizers Ltd. For the purpose of the study the data was collected from primary and secondary sources. Primary data was entered using SPSS (Statistical Package for Social Sciences) software and STATISTICA. Uni-variate and bi-variate tables were generated and chi-square tests and t-tests were carried out for testing the hypothesis at problem the level itself. The very purpose of this research is to know the opinion of the Employees on working conditions in Petrochemical and Fertilizer industries the effect of the development in industrial organizations and the development of productivity culture in the employees.

In recent years, economic transactions are carried out through electronic or online or cashless means all over the world especially in developed countries and developing countries like India. As a result of increased digital means of payment has brought down usage of cash transactions in the economy. Digital transactions have the features of speed, less cost, and comfort. A well functioning digital payment system has much relevance on overall economic activity, monetary policy, and financial stability of a country. This study tries to verify the impact of digital payments on the economic growth of India. The economic growth is measured through a proxy – real Gross Domestic Product. Digital payments are measured using Real Time Gross Settlement (RTGS), Clearing Corporation of India Ltd (CCIL) operated systems, paper clearing, retail electronic clearing, Card payments, and Prepaid Payment Instruments (PPIs). Data for digital payments and real GDP are collected from the year 2011 to 2019. Ordinary Least Square Regression, Auto-Regressive Distributed Lag (ADRL) co-integration approach and ARDL Bounds test are employed for the analysis. The study results reveal that digital payments impact economic growth significantly in the short run. But, digital payments don’t impact economic growth in the long-run.