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1
Allen, Rosamund Elizabeth. "Liposomes as drug delivery systems." Thesis, University of Essex, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.352982.
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2
Webster, Amy Philomena. "Epigenetics of response to biologic drug therapy in rheumatoid arthritis." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/epigenetics-of-response-to-biologic-drug-therapy-in-rheumatoid-arthritis(d1518a5c-ef1c-4d8f-b210-8a2342139a45).html.
Повний текст джерелаАнотація:
Background: Rheumatoid arthritis (RA) is a common complex autoimmune disorder which is influenced by both genetic and environmental factors. While multiple factors that influence susceptibility to and outcome of disease have been identified there is still a large proportion of missing heritability and limited understanding of disease pathogenesis. In recent years, biologic drug therapies have advanced treatment of RA; however good disease control is achieved in just 30% of patients, making identification of predictors of treatment response important. One area of research which is yet to be explored in relation to treatment response, and requires further evaluation in RA susceptibility, is epigenetics. Epigenetics is the study of modifications of the DNA which can influence gene expression but do not alter genetic sequence, and the most commonly studied epigenetic phenomenon, to date, is DNA methylation. Objectives: To identify DNA methylation signatures predictive of treatment response to anti-TNF biologics, to explore the role of DNA methylation in RA susceptibility using disease discordant monozygotic (MZ) twins, and to assess the effect of cryopreservation of cells on DNA methylation. Methods: Genome-wide DNA methylation levels were measured using the HumanMethylation450 BeadChip in pre-treatment whole blood DNA samples from individuals who had extremely good or extremely poor response to the anti-TNF therapies, etanercept and adalimumab, and in MZ twins discordant for RA (n=79 pairs). I also compared genome-wide methylation in cells which had been cryopreserved with fresh cells, to investigate if this technique is suitable for epigenetic investigations. Results: I identified four methylation sites which were significantly related to response to etanercept at a false discovery rate of 5%, the most significantly differentially methylated of which maps to the LRPAP1 gene (p=1.46E-8). Indeed, four other sites at the same locus also showed evidence for differential methylation indicating that this represents a differentially methylated region. No sites were significantly associated with response to adalimumab after correction for multiple testing. I identified subtle differences in DNA methylation between RA discordant twins. Although these were not statistically significant following adjustment for cell composition, one of the most differentially methylated positions mapped to the ZNF74 gene (p=4.97E-6), and replicated a methylation difference identified in the largest previous epigenome-wide association study of RA cases and unrelated healthy controls. I found that cryopreservation of cells does not significantly alter the methylome, an important observation that will impact upon design of future studies. Conclusions: In the largest studies of DNA methylation in RA treatment response and RA discordant MZ twins to date, I identified significant differential methylation in etanercept response, but not adalimumab response, and found small differences in methylation in RA discordant MZ twins. I also concluded that cryopreservation does not significantly alter the methylome.
3
Vugler, Alexander David. "Predicting anti-arthritic drug effects in collagen-induced arthritis using short-term mechanistic models of collagen II immunity." Thesis, Open University, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494617.
Повний текст джерелаАнотація:
Novel anti-arthritic drugs are often assessed in murine collagen-induced arthritis (CIA), which is a widely used pre-clinical model of rheumatoid arthritis. However, CIA studies are lengthy, development of arthritis is not synchronised and not all animals develop disease. Work conducted in this thesis addressed some of these issues by developing short-term mechanistic models of collagen II (CII) immunity. Drug effects on Cll-induced hypersensitivity, anti-CII antibodies and ex vivo CII stimulated CD4⁺ T cell proliferation in mice 14 days post-CII sensitisation were assessed and compared to their anti-arthritic effect in CIA.
4
Gregg, Catherine Nicola. "Structure-activity studies in non-steroidal anti-inflammatory drugs." Thesis, Liverpool John Moores University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238686.
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5
Speirs, A. "Gold chemistry and its use in the treatment of rheumatoid arthritis." Thesis, University of Strathclyde, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371977.
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6
Mina, James. "Hyaluronic acid based polymer drug conjugates for the treatment of rheumatoid arthritis." Thesis, University of the West of Scotland, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.739391.
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7
Kou, Eric Yao-Chung. "Child resistant drug packaging and arthritis can older consumers access their medications? /." Diss., Connect to online resource - MSU authorized users, 2006.
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8
Dunagan, Fiona M. "Non-steroidal anti-inflammatory drugs : pharmacokinetics and clinical response in rheumatoid arthritis." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236497.
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9
Singh, Jennifer. "Polymer-drug conjugates based on hyaluronic acid for the treatment of rheumatoid arthritis." Thesis, University of the West of Scotland, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415937.
Повний текст джерелаАнотація:
The work represents an initial appraisal ofhow polymer-drug conjugates based upon hyaluronic acid (HA) may behave at sites of inflammation relative to unmodified HA. Three polymer drug conjugates were synthesized in which a model drug, p-nitroaniline (pNA) has been joined to HA via a peptide spacer group containing alanine (ala) and valine (val). The conjugates are: HA-ala-pNA, HA-val-ala-pNA, and HA-ala-ala-ala-pNA. Each of the conjugates was subjected to the degradative effects of both hyaluronidase and hydroxyl radicals by the Fenton reaction (generated by Fe2 + ions and H202) . Hyaluronidase digestion was followed both by measurement of reducing hexosamine end-groups and rheologically. The degradative effects of hydroxyl radicals were followed by rheology alone. On incubation with hyaluronidase, end-group analysis showed that the rate of degradation of HA-ala-ala-ala-pNA preparation did not appear to differ significantly from that of unmodified HA. The hyaluronic acid-val-ala-pNA sample appeared to show a higher degradation rate than HA itself initially, after which it slowed relative to HA itself. With HA-ala-pNA the rate of hydrolysis of the HA backbone was found to be considerably lower that that observed for the other materials. Viscometric studies on the effects of hydroxyl radicals showed that, as expected, the rate of decrease in viscosity of the unmodified HA increased with increasing [Fe2J and that H202 alone showed a depolymerising effect on the HA in a concentration-dependent manner. The initial viscosity of the HA-ala-pNA and HA-ala-ala-ala-pNA was considerably lower than that of the unmodified H.-and hence any degradation was difficult to follow although some effects could Q\? observed with the higher concentrations of Fe::+. The HA-\al-ala-pNA conjugate showed a higher initial viscosity than native HA. The reason for this is not clear and would require more experimentation. Like the unmodified hyaluronic acid, on exposure to hydroxyl radicals, a rapid initial depolymerization of the conjugates was observed the rate of which increased with increasing concentration of Fe:!+.
10
Walker, K. A. "An investigation into the mechanisms responsible for altered drug disposition in adjuvant-induced arthritis." Thesis, University of Aberdeen, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372625.
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11
Peltomaa, Ritva. "Outcome of early rheumatoid arthritis : with special reference to early institution of drug treatment." Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/peltomaa2/.
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12
Barrie, Nicola. "ENDOCANNABINOID-BASED NANOPARTICLES TARGETED TO THE SYNOVIUM FOR THE TREATMENT OF ARTHRITIS." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/21185.
Повний текст джерелаАнотація:
Chronic inflammatory joint disease represents an emerging public health issue, occupying a sizeable proportion of the adult population in the industrialized world. Recently, there has been a resurgence of interest in marijuana and its natural and synthetic derivatives, cannabinoid receptor agonists and antagonists, as well as chemically related compounds, for their therapeutic potential as both an anti-inflammatory and analgesic. Whilst the benefits of endocannabinoid-based treatments appear promising, very few studies have investigated the use of the self-assembled nanoparticles (NPs) for targeted drug delivery. In this study, the nanostructure mesophase behaviour of a series of mixed monoethanolamide lipids of oleoylethanolamide (OEA) and linoylethanolamide (LEA) into higher order NP structures for the encapsulation and delivery of drugs was investigated. In addition to drug encapsulation, active targeting through the conjugation of a synovium-targeting peptide, HAP-1, to the surface of these NP’s was used to facilitate selective accumulation of therapeutic agents the inflamed joint. The inhibitory cytokine effects of these targeted NPs was demonstrated in vitro, and in vivo using an adjuvant induced arthritis model of inflammation. The ability to deliver endocannabinoid based NPs to specific sites of the body mediating pharmacological endocannabinoid-like effects to influence key physiological pathways, provides a novel drug delivery system and medicinal potential to treat many diseases in many fields of medicine in which inflammation is a key feature of the disease.
13
Nama, Nelisa Petronella Vuyo. "Potentiometric and spectrophotometric investigation of copper diclofenac as an anti inflammatory drug for the treatment of Rheumatoid Arthritis." Master's thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/6349.
Повний текст джерелаАнотація:
Includes bibliographical references.Copper and Diclofenac (DCL) separately, are used to alleviate inflammation associated with RA. It has been postulated that their combination would have a synergistic effect i.e., their combination would be more effective than when administered independently. Cu(II)-DCL system is studied potentiometrically in order to evaluate this hypothesis.
14
Baecklund, Eva. "Associations Between Rheumatoid Arthritis and Malignant Lymphomas." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5928.
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15
Aust, Julia Katharina. "Einfluss von Polymorphismen der Methylentetrahydrofolat Reduktase sowie des Multi-Drug-Resistance Proteins auf die Therapie der Rheumatoiden Arthritis mit Methotrexat." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-130248.
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16
Krasnitski, Raisa [Verfasser]. "Calprotectin bei DMARD (Disease Modifying Anti-Rheumatic Drug)-naiver früher rheumatoider Arthritis als Aktivitäts- und Verlaufsmarker unter Therapie / Raisa Krasnitski." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1228861064/34.
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17
He, Bing. "Toward precision medicine: a combination of leflunomide and ligustrazine attenuates progressive bone erosion in rheumatoid arthritis patients with high baseline serum c-reactive protein level." HKBU Institutional Repository, 2016. https://repository.hkbu.edu.hk/etd_oa/316.
Повний текст джерелаАнотація:
Leflunomide is widely prescribed for Rheumatoid Arthritis (RA) patients in China. However, a number of RA patients still demonstrated progressive bone erosion (PBE+) after receiving Leflunomide in our clinical data. Moreover, the PBE+ is predicted by high baseline serum CRP level (CRPBH). Further, the changes of serum bone resorption marker (Tartrate-resistant acid phosphatase 5b, TRAP5b) strongly correlated with those of CRP in PBE+ RA patients during Leflunomide treatment. Those were consistently observed in collagen-induced-arthritis (CIA) rats. To precisely address the issue, we screened a series of marketed drugs combined with Leflunomide to inhibit CRP production and CRP-related osteoclastic signaling pathway using bioinformatics analysis. Ligustrazine was postulated as an optimal candidate drug. In vitro studies demonstrated that the combination of Ligustrazine and Leflunomide not only suppressed hepatic CRP production, but also suppressed CRP-related osteoclastic signaling and osteoclast activities. In vivo studies showed that the combination attenuated bone erosion in CIA rats. Further, the randomized parallel controlled clinical trial in 120 CRPBH RA patients showed that the combination therapy reduced serum CRP levels and attenuated bone erosion in those patients (ChiCTR-TRC-10001014). Together, this work presents a precision combination therapy for PBE+ in CRPBH RA patients.
18
Smith, Christine. "Efficacy and Safety of Pharmacological and Non-Pharmacological Interventions in Juvenile Idiopathic Arthritis: A Series of Systematic Reviews and Network Meta-Analyses." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/35744.
Повний текст джерелаАнотація:
There is little head-to-head evidence comparing interventions available for juvenile idiopathic arthritis (JIA). This review involved a series of systematic reviews and network meta-analyses (NMAs) to evaluate the comparative efficacy and safety of pharmacological and non-pharmacological interventions among patients with JIA. Outcomes were the American College of Rheumatology Pediatric 30 (ACR Pedi 30) (disease response), its six composite outcomes, pain relief, health-related quality of life, and physical and emotional functioning. There was some evidence that etanercept had greater reduction in the number of joints with active arthritis compared to abatacept for polyarticular-course JIA and that canakinumab had improved ACR Pedi 30 over rilonacept. Non-pharmacological interventions showed no significant results for efficacy but were safe overall. Most included studies were low-quality and many were excluded from analysis because of unclear reporting or no results for outcomes of interest. As more studies are conducted this will improve the estimates from the NMAs.
19
Knight-Schrijver, Vincent. "Towards systems pharmacology models of druggable targets and disease mechanisms." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289731.
Повний текст джерелаАнотація:
The development of essential medicines is being slowed by a lack of efficiency in drug development as ninety per cent of drugs fail at some stage during clinical evaluation. This attrition in drug development is seen not because of a reduction in pharmaceutical research expenditure nor is it caused by a declining understanding of biology, if anything, these are both increasing. Instead, drugs are failing because we are unable to effectively predict how they will work before they are given to patients. This is due to limitations of the current methods used to evaluate a drug's toxicity and efficacy prior to its development. Quite simply, these methods do not account for the full complexity of biology in humans. Systems pharmacology models are a likely candidate for increasing the efficiency of drug discovery as they seek to comprehensively model the fundamental biology of disease mechanisms in a quantit- ative manner. They are computational models, designed and hailed as a strategy for making well-informed and cost effective decisions on drug viability and target druggability and therefore attempt to reduce this time-consuming and costly attrition. Using text mining and text classification I present a growing landscape of systems pharmacology models in literature growing from humble roots because of step-wise increases in our understanding of biology. Furthermore, I develop a case for the capability of systems pharmacology models in making predictions by constructing a model of interleukin-6 signalling for rheumatoid arthritis. This model shows that druggable target selection is not necessarily an intuitive task as it results in an emergent but unanswered hypothesis for safety concerns in a monoclonal antibody. Finally, I show that predictive classification models can also be used to explore gene expression data in a novel work flow by attempting to predict patient response classes to an influenza vaccine.
20
Tettey-Amlalo, Ralph Nii Okai. "In vitro release of ketoprofen from proprietary and extemporaneously manufactured gels." Thesis, Rhodes University, 2005. http://eprints.ru.ac.za/295/.
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21
Rafei, Moutih. "Fusokine design as novel therapeutic strategy for immunosuppression." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115882.
Повний текст джерелаАнотація:
The societal burden of autoimmune diseases and donor organ transplant rejection in developed countries reflects the lack of effective immune suppressive drugs. The main objective of my thesis was to develop novel fusion proteins targeting receptors linked to autoimmunity; strategies that will allow the suppression of autoreactive cells while sparing resting lymphocytes. Interleukin (IL) 15 has been demonstrated to exert its effects mainly on activated T-cells triggered via their T-cell receptor (TCR). Since we found that the fusion of granulocyte-macrophage colony stimulating factor (GMCSF) to IL15 - aka GIFT15 - paradoxically leads to aberrant signalling downstream of the IL15R and blocks interferon (IFN)-gamma secretion in a mixed lymphocyte reaction (MLR), we hypothesized to use this fusokine in proof-of-principle cell transplantation models and shown that GIFT15 can indeed block the rejection of allogeneic and xenogeneic cells in immunocompetent mice. Additionally, we found that ex vivo GIFT15 treatment of mouse splenocytes lead to the generation of regulatory B-cells (Bregs). These Bregs express high levels of MHCII, IL10 and are capable to block antigen (Ag)-presentation in vitro as third party bystander cells. Moreover, a single injection of these GIFT15-generated Bregs in mice with pre-developed experimental autoimmune encephalomyelitis (EAE) leads to long lasting remission of disease.Along those lines, we also found that mesenchymal stromal cells (MSCs) lead to the paracrine conversion of CCL2 to an antagonist form capable of specifically inhibiting plasma cells and activated Th17 cells. This mechanistic insight informed the design of a second class of suppression fusokine. Namely, the fusing of antagonist CCL2 to GMCSF - aka GMME1. We tested its potential use in autoimmune diseases such as EAE and rheumatoid arthritis (RA). We demonstrated that GMME1 leads to asymmetrical signalling and inhibition of plasma cells as well as Th17 EAE/RA-reactive CD4 T-cells. The net outcome of these pharmacological effects is the selective depletion of CCR2-reactive T-cells as demonstrated both in vitro and in vivo.
Overall, our data support the use of our fusion proteins as part of a powerful and specific immunosuppressive strategy either as directly injectable protein biopharmaceuticals or through the ex vivo generation of autologous Bregs in the case of GIFT15.
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Mendes, Mariana Trivilin. "Efeito de drogas sintéticas inibidoras do fator de necrose tumoral alfa na artrite reumatoide em ratos." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/41/41135/tde-28102017-113448/.
Повний текст джерелаАнотація:
A artrite reumatoide (AR) é uma doença autoimune, inflamatória, crônica, sistêmica e de etiologia desconhecida que pode ser induzida experimentalmente em animais por administração de colágeno e adjuvante (CIA). Os medicamentos biológicos contra o fator de necrose tumoral (TNF)-α são indicações terapêuticas atualmente consolidadas para os casos mais severos de AR. As limitações ao uso dessa classe de medicamentos têm sido o alto custo e a dificuldade em fabricar genéricos ou similares com composição, qualidade e desempenho equivalentes na mesma dose e via de administração. O presente estudo avaliou a hipótese de que drogas sintéticas que inibam a produção de TNF-α e / ou fatores relacionados teriam potencial para tornarem-se terapias complementares ou alternativas eficientes para esta doença. Para isso, foram utilizados ratos submetidos ao modelo CIA e tratados cronicamente com pentoxifilina (PTX), rolipram (ROL), talidomida (TAL) e rupatadina (RUP). Um tratamento com prednisolona (PRED) foi também efetuado para avaliar sua influência na eventual ação antiartrítica de PTX, ROL, TAL e RUP, de modo a mimetizar seu efeito imunossupressor, quando administrada agudamente (AG) antes de medicamentos biológicos, bem como pelo seu conhecido efeito anti-inflamatório, quando administrada cronicamente (CR) no tratamento da AR. O desenvolvimento da AR e a efetividade dessas drogas sobre a AR foram avaliadas, de forma seletiva e sequencial, por meio da detecção de eritema e cianose, bem como medidas de edema, massa corporal, hemograma, TNF-α no plasma, fator reumatoide (FR) e anticorpo antinuclear (ANA) no soro, interleucina (IL)-1β e IL-6 no soro e líquido sinovial, atividade de aminopeptidase básica (APB) na fração solúvel (FS) do tecido sinovial (TS) e de células mononucleares do sangue periférico (PBMCs), densitometria óssea e análise histológica. A hepatotoxicidade dessas drogas foi avaliada pelas medidas de alanina-transaminase (ALT) e aspartato-transaminase (AST) no plasma. A AR caracterizou-se pelo aumento de TNF-α plasmático e de IL-1β e IL-6 no líquido sinovial, alterações histológicas na articulação tíbio-tarsal, bem como edema, cianose, eritema, diminuição de linfócitos e atividade APB de FS aumentada no TS e diminuída em PBMCs. A AR aumentou ALT e AST. O tratamento com PRED crônico promoveu um efeito antiedematogênico. O coquetel (MIX de PTX+ROL+RUP+TAL) também apresentou efeito antiedematogênico. A administração concomitante de PRED AG ou PRED CR com MIX não produziu sinergismo ou potenciação do efeito antiedematogênico da administração isolada do MIX ou da PRED crônica. Além do MIX, ROL e TAL diminuíram o edema. MIX, ROL e TAL melhoraram TNF-α no plasma e APB na FS do TS e não causaram hepatotoxicidade, tal como refletido nos níveis de ALT e AST. TAL recuperou ALT e AST, sem alteração do hemograma. Uma vez que PTX e RUP não apresentaram efeito antiedematogênico, ROL e TAL foram hipotetizados como os prováveis responsáveis pela atividade antiartrítica do MIX. Então, os tratamentos com ROL, TAL e ROL+TAL foram selecionados para avaliação da histologia óssea e medidas de parâmetros diferenciais entre animais controles sadios e artríticos. Esta avaliação mostrou que o tratamento isolado da AR com ROL ou TAL não alterou IL-6, mas recuperou IL-1β no líquido sinovial, efeitos esses que não se diferenciaram do tratamento combinado de ROL+TAL, exceto pelo fato de que essa combinação também diminuiu a massa corporal. TAL se destacou por seu efeito hepatoprotetor nos animais AR. Considerando os efeitos conhecidos de RUP, PTX, TAL e ROL é possível hipotetizar que a ação antiartrítica de TAL e ROL deve-se à inibição da síntese de TNF-α decorrente da inibição de PDE4 em suas principais fontes celulares. Os dados deste estudo prospectivo fornecem subsídios adicionais que estimulam a realização de novos ensaios clínicos, mais amplos e sistematizados, sobre os efeitos antiartríticos de ROL e TAL. Conclui-se que o uso isolado de TAL emerge como uma alternativa terapêutica econômica, simples e eficaz para a AR, enquanto a combinação de ROL+TAL pode ser uma opção viável para portadores de AR com sobrepeso ou obesidadeRheumatoid arthritis (RA) is an autoimmune, inflammatory, chronic and systemic disease with unknown etiology that can be experimentally induced in animals by administration of collagen and adjuvant (CIA). Biological drugs against tumor necrosis factor (TNF)- α are therapeutic indications currently consolidated for the most severe cases of RA. The limitations for the use of this class of drugs have been the high cost and the difficulty to manufacture a generic or similar ones with equivalent composition, quality and performance under the same dosage and route of administration. The present study evaluated the hypothesis that synthetic drugs that inhibit the production of TNF-α and/or related factors would have potential to become efficient complementary or alternative therapies for this disease. For this purpose, male rats submitted to the CIA model were chronically treated with pentoxifylline (PTX), rolipram (ROL), thalidomide (TAL) and rupatadine (RUP). The treatment with prednisolone (PRED) was also performed to evaluate its influence on the possible antiarthritic action of PTX, ROL, TAL and RUP, in order to mimic its immunosuppressive effect when acutely (AG) administered prior to biological drugs, as well as due to its known anti-inflammatory effect when administered chronically (CR) to treat RA. The development of RA and the efficacy of these drugs on RA were evaluated, by selective and sequential ways, through the detection of erythema and cyanosis, as well as measurements of edema, body mass, hemogram, plasma TNF-α, rheumatoid factor (FR) and anti-nuclear antibody (ANA) in serum, interleukin (IL)-1β and IL-6 in serum and synovial fluid, basic aminopeptidase activity (APB) in soluble fraction (FS) from synovial tissue (TS) and from peripheral blood mononuclear cells (PBMCs), bone densitometry and histological analysis. The hepatotoxicity of these drugs was evaluated by measurements of alanine-transaminase (ALT) and aspartate-transaminase (AST). RA was characterized by increased TNF-α in plasma and IL-1β and IL-6 in synovial fluid, histological alterations in the tibio-tarsal joint, as well as edema, cyanosis, erythema, decreased lymphocyte number and increased APB activity in TS and decreased APB activity in PBMCs. RA produced increased ALT and AST. As expected, the chronic treatment with PRED promoted an antiedematogenic effect. The cocktail (MIX of PTX+ROL+RUP+TAL) also presented antiedematogenic effect. Concomitant administration of acute or chronic PRED with MIX did not produce synergism or potentiation of the antiedematogenic effect due to the single administration of MIX or chronic PRED. In addition to MIX, ROL and TAL were also antiedematogenic. MIX, ROL and TAL ameliorated plasma TNF-α and APB in FS from TS without hepatotoxicity, as reflected by ALT and AST levels. TAL recovered ALT and AST, but it did not affect the hemogram. Since PTX and RUP did not present antiedematogenic effects, ROL and TAL were hypothesized as probable responsible for the antiarthritic activity of MIX. Thus, the treatments with ROL, TAL and ROL+TAL were selected for evaluation of bone histology and measurements of differential parameters between healthy control and arthritic animals. This evaluation showed that the treatment of RA with ROL or TAL alone did not alter IL-6 levels, but recovered IL-1β in the synovial fluid. Both these effects were not different from those of the concomitant treatment with ROL+TAL, except that this combination also decreases the body mass. TAL stands out for its hepatoprotective effect in RA animals. Considering the known effects of RUP, PTX, TAL and ROL it can be hypothesized that antiarthritic action of TAL and ROL is due to the inhibition of TNF-α synthesis as consequence of its inhibition in its main cellular sources by PDE4. Data from this prospective study provide additional subsidies that stimulate further and more comprehensive clinical trials on the antiarthritic effects of ROL and TAL. In conclusion, the treatment with TAL alone emerges as an economical, simple and effective therapeutical alternative for RA, while the combination of ROL+TAL can be a viable option for RA sufferers with overweight or obesity
23
Mohajane, Mamohale. "Dipeptides as potential anti-flammatory drugs for rheumatoid arthritis." Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/6340.
Повний текст джерелаАнотація:
Includes abstract.Includes bibliographical references.
The H⁺ and Cu²⁺ equilibria of four glycine peptides (glycyl-glycine, glycyl-L-leucine, glycyl-L-phenylalanine and glycyl-L-histidine) and four sarcosine peptides (sarcosylglycine, sarcosyl-L-leucine, sarcosyl-L-phenylalanine and sarcosyl-L-histidine) have been studied using glass electrode potentiometry and isothermal titration calorimetry at 25 °C and an ionic strength 0.15 M (NaCl). The terminal amine of the sarcosine peptides is more basic than the glycine analogues. The methyl group on the terminal amine (for sarcosine peptides) does not affect the stability constants of the ML species, significantly. Log K for ML species for all the Cu(II)/peptides complexes ranged between 5.79 and 6.54, except for glycyl-L-histidine that showed log KML = 9.16. Heat accompanying the formation of ML for all the species ranged between -5.1 kcal mol⁻¹ and-6.6 kcal mol⁻¹, except for glycyl-L-histidine that showed ΔHML = -3.6 kcal.mol⁻¹. Structures for the different species in solution were postulated based on nuclear magnetic resonance and ultraviolet-visible spectrophotometry data. Molecular mechanics was used to investigate the possible structures. The minimum energy of the trans form of most the complexes was less than the cis form of the complexes.
24
Bondeson, Jan. "Effects of disease-modifying antirheumatic drugs on macrophage signal transduction and the induction of proinflammatory cytokines." Lund : Section of Molecular Pathogenesis, Dept. of Cell and Molecular Biology, Lund University, 1996. http://books.google.com/books?id=dgxsAAAAMAAJ.
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25
Beverly, Bart J. "Mechanism of action of aurothioalkyl antiarthritic drugs : role of myeloproxidase /." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487330761219101.
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26
Aird, Sheelagh Ann. "The pharmacokinetics of D-penicillamine in normal and adjuvant arthritic rats." Thesis, University of Bath, 1987. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376332.
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27
Coste, Emmanuel. "Development of small molecules as anti-inflammatory and anti-resorptive drugs." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/9941.
Повний текст джерелаАнотація:
Rheumatoid arthritis is an auto-immune inflammatory disease that leads to stiff and swollen joints. Patients also have severe bone destruction of the affected joints and another common symptom of rheumatoid arthritis is a generalised bone loss that can lead to osteoporosis. Currently, there are many treatments for rheumatoid arthritis, which provide a recession of the inflammatory symptoms. However, none of these treatments are able to provide a complete protection against the rheumatoid arthritis-induced bone loss. Furthermore, the most effective available treatments such as glucocorticoids or the new biological drugs are not optimal since they either cause severe side effects or are very expensive and difficult to produce. Hence, there is a real need for new cost-effective treatments that can act on both inflammation and bone loss symptoms of rheumatoid arthritis. ABD compounds are small molecules, relatively easy to synthesize at reasonable cost. In this thesis, I discuss the effects of these small molecules on both rheumatoid arthritis-induced inflammation and bone loss. Daily treatments with the ketones ABD328 and ABD345, or with the sulphonamide ABD455 prevent inflammation in an animal model of rheumatoid arthritis. Furthermore, micro-CT and histology analysis showed that these treatments also provide a reliable protection against bone destruction of affected joints and generalised bone loss. In vitro data showed that this protective effect on bone was osteoclast specific. Indeed, Ishow here that treatment of other bone cells (such as osteoblasts or macrophages) with ABD compounds does not affect their biology. The mechanism of action of these compounds has also been studied and I show here that ABD compounds inhibit both inflammation and osteoclastogenesis by inhibiting the signalling pathways that are activated in response to pro-inflammatory cytokines such as TNF . This work led to the design and synthesis of further improved compounds, such as ABD599, that are currently considered as very interesting candidates for clinical trials. In conclusion, the ABD compounds, as small cost-effective molecules, represent a novel class of rheumatoid arthritis treatments by acting on both inflammation and bone loss symptoms of the disease.
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Mohamed, Ahmed A. "Redox studies on the anti-rheumatoid arthritis gold drugs : Auranofin and Solganol /." Fogler Library, University of Maine, 2000. http://www.library.umaine.edu/theses/pdf/MohamedAA2000.pdf.
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29
Frean, Stephen Philip. "Effects of anti-arthritic drugs on equine articular tissue metabolism." Thesis, Royal Veterinary College (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263731.
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30
Garrett, Neil Edward. "Substance P and experimental joint inflammation." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244679.
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31
Mulhearn, Ben. "Identifying immune biomarkers to predict treatment response to biologic drugs in rheumatoid arthritis." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/identifying-immune-biomarkers-to-predict-treatment-response-to-biologic-drugs-in-rheumatoid-arthritis(c311fc8c-4239-444a-9912-ddd4fde5f7fa).html.
Повний текст джерелаАнотація:
Rheumatoid arthritis (RA) is a chronic, heterogeneous, autoimmune disease that causes inflammation of synovial joints leading to pain, stiffness and swelling. If left untreated, RA results in irreversible joint destruction and long term disability. Initial treatment with glucocorticoids and other immunosuppressive agents suppresses inflammation. However, many of these drugs are not well-tolerated due to extensive side effects or are simply ineffective. The discovery of tumour necrosis factor-α (TNF) as a key mediator of inflammation in RA led to the development of monoclonal anti-TNF antibody therapy. Since then, other biologic drugs targeting immune pathways have been developed for RA, including interleukin-6 (IL-6) blockade, B cell depletion, and T cell co-stimulation blockade. Not all patients will respond to their first biologic drug and currently there is no way to predict which patient will respond to each different class of drug. Generally, 3 – 6 months are required to determine clinical efficacy, during which time joint inflammation proceeds. Therefore, discovering biomarkers to predict treatment response is a research priority. Biologic drugs target immune pathways. As single cell technology advances and has increasing capacity to identify subtle changes in many cell subsets, I hypothesise that studying the blood immune cell landscape will define cellular biomarker profiles relevant to each individual patient’s disease.
32
Tsumbu, Evariste Umba. "Evaluation of tissue permeability of novel copper based anti-arthritic drugs." Master's thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/12361.
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33
Rinaudo-Gaujous, Mélanie. "Etude de marqueurs biologiques prédictifs de la perte de réponse aux anti-TNF." Thesis, Saint-Etienne, 2015. http://www.theses.fr/2015STET016T/document.
Повний текст джерелаАнотація:
L’utilisation d’agents anti-TNF a grandement amélioré la prise en charge de certaines maladies inflammatoires chroniques comme la polyarthrite rhumatoïde (PR) ou les maladies inflammatoires chroniques de l’intestin (MICI). Cependant, le quart des patients environ ne vont pas répondre au traitement ou présenteront une perte de réponse secondaire. Des marqueurs prédictifs de réponse sont nécessaires afin limiter les effets secondaires et les coûts inutiles en ciblant les patients qui pourraient être améliorés par les anti-TNF. Ces travaux de recherche se sont dans un premier temps concentrés sur l’importance de l’immunogénicité de ces traitements. Des anticorps anti-médicaments (ADAs) étaient bien associés à un taux bas d’anti-TNF avec des conséquences cliniques en termes de perte de réponse clinique et d’absence de cicatrisation muqueuse dans les MICI. Des seuils cliniques d’interprétation des tests biologiques pour la détection du médicament et de ses anticorps ont pu être définis et correspondent à 4.9 μg/ml pour l’infliximab et 200 ng/ml pour les ADAs. Ces résultats obtenus par ELISA sont bien corrélés avec les tests fonctionnels réalisés en parallèle et confirment l’intérêt de cette technique dans ce dépistage. Les ADAs étaient diminués par traitement immunosuppresseur concomitant. Ensuite, la persistance d’une infection chronique mise en évidence par des anticorps anti-bactériens a été évaluée en tant que marqueur prédictif de réponse aux anti-TNF. Aucun résultat statistiquement significatif n’a pu être relevé sur ces premières données, que ça soit pour les anticorps dirigés contre la flore intestinale pour les MICI ou contre le microbiote oral dans la PR. Seul un taux élevé de MMP-3 à l’initiation de l’infliximab chez les patients PR prédisait d’une bonne réponse clinique selon les critères de l’EULAR par la suiteThe use of anti-TNF agents has greatly improved the management of chronic inflammatory diseases such as rheumatoid arthritis (RA), or chronic inflammatory bowel disease (IBD). However, about a quarter of patients will not respond to treatment or will present a secondary loss of response. Predictive biomarkers of response are needed to reduce side effects and unnecessary costs by targeting patients that could be improved by anti-TNF. This research work was initially focused on the importance of immunogenicity of these treatments. Anti-drug antibodies (ADAs) were well associated with low levels of anti-TNF with clinical consequences in terms of loss of clinical response and absence of mucosal healing in IBD. Clinical thresholds for drug and ADAs have been defined and correspond to 4.9 μg/ml for infliximab and 200 ng/ml for ADAS. These results obtained by ELISA correlate well with functional tests done in parallel, and confirm the value of this technique for screening. The ADAs were decreased with concomitant immunosuppressive therapy. Then, the persistence of chronic infection as evidenced by anti-bacterial antibody was evaluated as a predictive marker for response to anti-TNF. No statistically significant results could be raised on these first data, for antibodies against the intestinal flora in IBD or against the oral microbiota in RA. Only high levels of MMP-3 at the initiation of infliximab in RA patients predicted a good clinical response according to the EULAR criteria
34
Hatch, Lashley. "Statistical Information Included in Labeling for Disease-Modifying Anti-Rheumatic Drugs for Rheumatoid Arthritis." The University of Arizona, 2012. http://hdl.handle.net/10150/623641.
Повний текст джерелаАнотація:
Class of 2012Specific Aims: To evaluate the presence of statistical information from clinical studies in official product labeling specific for disease-modifying anti-rheumatic drugs (DMARDs) used in the treatment of rheumatoid arthritis. Methods: Data were abstracted from official product labeling DMARDs with FDA approval for treatment of rheumatoid arthritis. Each document was examined for the presence of statement regarding a priori type 1 error rate, p-values, and measures of variance. Medications were classified as either biologic or non-biologic. Main Results: A total of 14 DMARDs, 7 biologics (50%) and 7 non-biologics (50%), were found to be FDA approved for the treatment of rheumatoid arthritis. Primary outcomes consisted of American College of Rheumatology (ACR) response rates, radiographic changes, and health assessment questionnaire score (HAQ). Any measure of variance and the presence of a p-value were both found in six (43%) of the drug labels. Inclusion of p- values was found to be significantly greater in biologics compared to non-biologics for both ACR and radiographic results. Inclusion of variance was found to be significantly greater in biologics compared to non-biologics for radiographic changes only. No package inserts contained statements regarding the a priori type I error rate. Conclusions: Measures of variance are not frequently included in product labeling for either biologic or non-biologic DMARDs. However, inclusion of variance and p-values for ACR response rates and radiographic changes were more likely to be reported for biologics therapies as compared to non-biologics. A statement regarding Type 1 error rates were absent from labels regardless of outcome assessed.
35
Hatch, Lashley, and Daniel C. Malone. "Statistical Information Included in Labeling for Disease-Modifying Anti-Rheumatic Drugs for Rheumatoid Arthritis." The University of Arizona, 2012. http://hdl.handle.net/10150/614497.
Повний текст джерелаАнотація:
Class of 2012 AbstractSpecific Aims: To evaluate the presence of statistical information from clinical studies in official product labeling specific for disease-modifying anti-rheumatic drugs (DMARDs) used in the treatment of rheumatoid arthritis. Methods: Data were abstracted from official product labeling DMARDs with FDA approval for treatment of rheumatoid arthritis. Each document was examined for the presence of statement regarding a priori type 1 error rate, p-values, and measures of variance. Medications were classified as either biologic or non-biologic. Main Results: A total of 14 DMARDs, 7 biologics (50%) and 7 non-biologics (50%), were found to be FDA approved for the treatment of rheumatoid arthritis. Primary outcomes consisted of American College of Rheumatology (ACR) response rates, radiographic changes, and health assessment questionnaire score (HAQ). Any measure of variance and the presence of a p-value were both found in six (43%) of the drug labels. Inclusion of p-values was found to be significantly greater in biologics compared to non-biologics for both ACR and radiographic results. Inclusion of variance was found to be significantly greater in biologics compared to non-biologics for radiographic changes only. No package inserts contained statements regarding the a priori type I error rate. Conclusions: Measures of variance are not frequently included in product labeling for either biologic or non-biologic DMARDs. However, inclusion of variance and p-values for ACR response rates and radiographic changes were more likely to be reported for biologics therapies as compared to non-biologics. A statement regarding Type 1 error rates were absent from labels regardless of outcome assessed.
36
Roux, Ilanca. "Prescribing patterns of biologic immunomodulating medicine in the South African private health care sector / Ilanca Roux." Thesis, North-West University, 2010. http://hdl.handle.net/10394/4936.
Повний текст джерелаАнотація:
Advances in molecular immunology and rapid technical evolution during the past two
decades have led to a new class of medicines called biologics. Recently, a large number of
biologics, or biologic immunomodulators, directed towards an array of immune–mediated
diseases, have entered the market. This has lead to a dramatic change in the
immunotherapy of autoimmune diseases, as biologics present new potential to improve or
substitute conventional immunosuppressive therapies. According to literature, biologics are
used by only a small number of a health plan’s members, (approximately one per cent), but a
single occurrence can be relatively expensive. Furthermore, there is an indication that the
frequency of use and cost of biologics are on the rise, and as more biologics enter the
market, health plans and employers face the challenge of controlling costs while ensuring
that biologics are affordable.
The general objective of this study was to determine the prevalence and cost of biologic
immunomodulating medicine in the treatment of certain autoimmune diseases during the
period 2005 to 2008 in a section of the private health care sector of South Africa, by
employing a medicine claims database as a source to obtain necessary information.
A quantitative, retrospective drug utilisation review (rDUR) was performed on computerised
medication records (medicine claims data) for four consecutive years (i.e. 2005 to 2008)
provided by a pharmacy benefit management company (PBM). The study population
consisted of all patients on the database who received at least one medicine item with
adalimumab, etanercept, infliximab, interferon beta–1a, interferon 1–b or rituximab as active
ingredient and who were diagnosed with either rheumatoid arthritis (RA), multiple sclerosis
(MS) or Crohn’s disease between 1 January 2005 and 31 December 2008.
Between 2005 and 2008, an average of 1,305,201 patients appeared on the total database,
and of these 0.055% (n = 713) received biologic immunomodulating medicine. More than two
thirds of biological users were female and most patients who received these medicine items
were between the ages of 39 and 64 years, followed by those patients aged between 25 and 39 years. Biologic immunomodulating medicine items (n = 11,914) and biologic prescriptions
(n = 9,537) represented 0.016% of the total number of medicine items (N = 76,129,173) and
0.030% of the total number of prescriptions (N = 31,985,153). The percentage contribution
of biologic immunomodulators to the total number of medicine items and prescriptions on the
total database increased each year, and in four years’ time the percentage of all the
medicine items on the total database that included biologic immunomodulators had tripled,
from 0.009% to 0.023%.
The total cost of biologic immunomodulating medicine accounted for 1.278% of the total cost
(N = R7, 483,759,176.23) of all medication claimed through the PBM between 2005 and
2008. The percentage contribution of biologic immunomodulators to the total medicine
expenditure also increased from one year to another for the four–year study period. The
average cost of a biologic immunomodulating medicine item increased with 71.10% from
2005 (R5602.71 ± 2166.61) to (R9586.25 ± 5956.56) in 2008. The CPI for biologic
immunomodulators, (CPI = 60.00 for 2005; CPI = 74.62.17 for 2006; CPI = 85.26 for 2007;
and CPI = 86.96 for 2008) indicated that biologic immunomodulating medicine items were
relatively expensive and the d–value between the average cost per biologic
immunomodulator and the average cost per non–biological medicine item (d–value = 2.54 in
2005, d–value = 3.32 in 2006, d–value = 2.23 in 2007 and d–value = 1.59 in 2008) furthermore
indicated that the impact of biological therapies was large and practically significant.
Rheumatoid arthritis patients represented 19.78% of the total number of patients (n = 713)
who claimed the biologic immunomodulators during the four–year period, MS patients (n =
172) represented 24.12% and Crohn’s patients (n = 11) represented 1.5%. Biological drugs
prescribed to RA patients represented 0.28% (n = R20, 708,818.82) of the total cost (N = R7,
483,759,176.23) of all medication claimed through the PBM during the four–year period, while
those prescribed to MS patients represented 0.41% (R30, 922,520.07) and those prescribed
to Crohn’s disease patients represented 0.015% (R1, 108,568.02).
Although biologic immunomodulating medicine items used in the treatment of RA, MS and
Crohn’s disease are relatively expensive, it seems that the number of other medication
prescribed to patients with these diseases decreased after treatment with biologics, which
may influence the medicine treatment cost of these patients.
It can be concluded that even though biologic immunomodulators are used by only a very
small percentage of the total patient population in a section of the private health care sector
of South Africa, they are relatively expensive and have a considerable impact not only the
medical aid scheme, but also on the patient.Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.
37
Leblanc, Daren James. "Thiol complexes of gold(I), structure and chemistry of the gold based anti-arthritis drugs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0018/NQ30153.pdf.
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38
LeBlanc, Daren James. "Thiol complexes of gold(I) : structure and chemistry of the gold based anti-arthritis drugs /." *McMaster only, 1996.
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39
Warhurst, Jannette. "DRUMBEAT© for arthritis “ a shared purpose” rather than a “lonely struggle”." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2021. https://ro.ecu.edu.au/theses/2452.
Повний текст джерелаАнотація:
Australia is regarded as a healthy nation, with life expectancy one of the highest in the world. Yet the latest National Health Survey tells a very different story. Almost 50% of Australians are now living with one or more chronic conditions, with arthritis and other musculoskeletal (MSK) conditions representing the most expensive chronic disease group in Australia. As the leading cause of chronic pain and second most common cause of disability and early retirement due to ill health in Australia, Arthritis is costing the economy over $7 billion a year, in addition to over $1.1 billion in extra welfare costs and lost tax revenue. Although personal, social and economic burdens of arthritis are immense they tend to be poorly recognised, with government investment considerably lower than for any other major disease group, with the exception of asthma.
While very common, arthritis is not well understood. Prevailing myths inaccurately portray arthritis as an old person's disease and an inevitable part of aging. More than 150 types of arthritis and related MSK conditions have been described; classified as either inflammatory, or non-inflammatory. Osteoarthritis (OA) is the most common type of non-inflammatory, characterised by progressive damage to cartilage and other joint tissues. Rheumatoid arthritis (RA) is the prototypical inflammatory arthritis, followed by gout, psoriatic arthritis (PsA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (lupus), among others. Classified as chronic autoimmune disorders, the symptoms of inflammatory arthritis (IA) are not localised to the damaged joint, and individuals may also experience fever, weakness, and organ damage, in addition to the stiffness and pain in the joints. As the sample size of this pilot study is small, it was decided to not recruit from the entire target population but rather to focus on those individuals living with IA.
The measure of prevalence of arthritis and other MSK conditions in Australia poses a challenge as there are wide variations in condition specific data. A snapshot from the Australian Institute of Health and Welfare (AIHW) and the Australian Bureau of Statistics (ABS) indicates almost 4 million Australians, 1 in 6 people, live with some form of arthritis – this number has almost doubled since the 1950’s and is expected to significantly increase by 2030. Limited national statistics and publications show an estimated 456,000 Australians (1.9% of the total population) with RA; JIA as affecting around 1 child in every 1,000 aged 0–15; PsA occurring in up to 30% of people who have psoriasis, a common skin disorder that affects approximately 2% of the population; and suggest AS affects one in 200 Australians. The limited data relating to incidence, treatment, costs and outcomes of the many types of arthritis is seen as a major barrier to recognition of the impact and potential severity of the disease group by the general public, clinicians and policymakers.
statistics and publications show an estimated 456,000 Australians (1.9% of the total population) with RA; JIA as affecting around 1 child in every 1,000 aged 0–15; PsA occurring in up to 30% of people who have psoriasis, a common skin disorder that affects approximately 2% of the population; and suggest AS affects one in 200 Australians. The limited data relating to incidence, treatment, costs and outcomes of the many types of arthritis is seen as a major barrier to recognition of the impact and potential severity of the disease group by the general public, clinicians and policymakers.
The study investigated whether individuals living with various forms of IA could improve levels of self-management by participating in a drumming intervention based on the Holyoake DRUMBEAT (Discovering Relationships Using Music -Beliefs, Emotions, Attitudes, & Thoughts) format, that uses hand drumming to allow participants to explore and engage connections between making music together as a group and development of emotional skills, such as self-regulation and self-confidence.
The initial aim of the study was to help understand the unique experiences of those individuals living with IA, as expressed by research participants in this study. The subsequent and overarching aims of the research were to investigate what benefits persons living with IA might derive through their participation in innovative and novel hand-drumming programs such as DRUMBEAT.
Seven participants with varied forms of IA were invited to take part in a 6-week hand-drumming intervention based on the Holyoake DRUMBEAT program. The 2.5hour weekly sessions were held in 2019 at the headquarters of AOWA. Each session consisted of playing djembe drums and/or percussion, and discussions to facilitate effective interaction between participants. Additionally, the inclusion of breaks before, after and during the sessions was an important consideration to encourage social interaction with others possibly facing similar challenges in life. Ad hoc adaptations led to change in peripheral delivery components of the program so as to suit the participants’ abilities, rather than their disabilities. Modification was about flexibility and this is inherent in the way the sessions were delivered. The core content of the program remained the same. Exclusion criteria included presence of a major depressive disorder, or a previously diagnosed depressive disorder that had not been stabilised through treatment; or presence of any co-existing musculoskeletal conditions that prevented participation.
A sequential mixed-methods action research design was adopted for this exploratory health promotion intervention. The integration of mixed methods and action research allowed for various research tools to be used: researcher observations; weekly transcripts; one-on-one interviews; final focus group transcripts; and pre, interim, and post – program questionnaires. Depression, anxiety and quality of life (QoL) were assessed using the RAND 36-Item Health Survey 1.0 and the Hospital Anxiety and Depression scale (HADS). In analysing the results, each participant’s general self-efficacy was assessed using the Rheumatoid Arthritis Self-Efficacy (RASE) questionnaire and the Locus of Control of Behaviour Scale (LoCBS). The UCLA Loneliness Scale (Version 3) was utilised to measure loneliness and social support, together with a simple, four-item Session Rating Scale (SRS) administered, scored and discussed at the end of each session, to get real-time feedback from participants. The Visual Analogue Scale (VAS) was also completed at the end of each session to help capture any differences in pain intensity and / or severity, pre- and post-drumming.
Quantitative results show depression was significantly lower from baseline to follow up. Depression had decreased from a mean (Median; SD; IQR) of 6.29 (7.0; 3.15; 5.0) to 4.42 (5.0; 2.82; 5.0) during the 6-week intervention. Anxiety reduced from a mean (Median; SD; IQR) of 7.86 (7.0; 4.98; 10.0) to 7.14 (7.0; 4.91; 9.0). Statistically significant improvements in QoL scores were observed in physical functioning from a mean (Median; SD; IQR) of 55 (65; 20.41; 30) to 65 (75; 18.26; 25). Trends in improvement in role physical / role emotional scale was noted, together with reduced bodily pain. There were smaller non-significant improvements in energy / fatigue, emotional wellbeing and general health. All QoL measures appeared to improve, though all but physical did not reach statistical significance due to small sample size and inadequate exposure to the intervention for some participants. The study encountered poor participation rates, with fatigue and lack of confidence identified as the main reasons for non-attendance. Only 28.57% (n=2) of the participants completed the full 6-week DRUMBEAT program, with 57.14% (n=4) completing four, or more sessions. Social function and differences in loneliness, as measured by UCLA scale (version 3) were the only scales to remain unchanged. The degree of change was also not significant in self‐report measures of locus of control. The majority of participants (n=6) indicated small non-significant improvements in self-efficacy. Qualitative analysis revealed a significant sense of community and by week two there was a noticeable sense of bonding within the group. In addition to community features the qualitative analysis revealed some positive signs of improvement in multiple domains of social-emotional behaviour.
We conclude that the drumming intervention may have a beneficial effect on both mental and physical self-reported health, in the short term, in an IA population. These findings add to the growing evidence on how engagement in a group drumming intervention, such as DRUMBEAT may influence participants to utilise experiences drawn from their own lives to find solutions to challenges, and promote healthy behaviour changes.
To support these results, further studies are needed to measure outcomes and the potential usefulness of incorporating DRUMBEAT into a successful management strategy of IA. This will allow for the opportunity to produce more evidence and determine the effects of outside factors.
While appreciating the role of medications to alleviate symptoms, clearly the current approach to the management of chronic conditions, such as IA, is not working and therein presents an opportunity for innovative interventions such as DRUMBEAT. Based upon the findings and recommendations of this study, DRUMBEAT appears to be an easily accessible, fun, sustainable program that may help participants gain the social support and skills necessary for them to thrive, learn, work, earn and participate in community life.
40
Mhlambiso, Zizile. "Design of novel copper(II) based anti-inflammatory drugs for the elevation associated with Rheumatoid Arthritis." Master's thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/9280.
Повний текст джерелаАнотація:
Includes bibliographical references.It has been shown that copper complexes are able to alleviate inflammation associated with Rheumatoid Arthritis (RA). Serum copper levels are elevated in RA and it has been postulated that endogenous copper might have a protective function in chronic inflammatory conditions. In designing Cu(I1) anti-inflammatory drugs, one needs to know the stability constants of the ligand together with Cu(I1) and the competitive metal ions, Zn(I1) and Ca(I1) in blood plasma. For this purpose glass electrode potentiometry, infrared (lR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, UV/Visible spectroscopy as well as blood plasma modelling were used to explore the coordination chemistry of a newly designed ligand, PCUL (Bis-(3- aminoethy-2-aminomethylpyridine )-oxahexacyclo-dodecane). PCUL protonation and formation constants with Cu(I1) and Zn(I1) were investigated by potentiometric analysis at 2SoC and 0.ISmol/dm3 Na + (CI) The potentiometric analysis showed that CU(I1) formed far more stable complexes at physiological pH with PCUL than the in vivo competitor Zn(I1). In this study the IR spectroscopic analysis was used to determine the Cu(I1)-PCUL complexation sequence. The IR spectra show that the central amines are coordinated to the metal ion first. The small frequency shift between pH 4.02 to 6.91 proves that the pyridyl nitrogen atoms are also coordinated to CU(I1).
41
Madeira, Jocelyn Marie. "Old drugs in a new light : investigating the gold Rheumatoid Arthritis medications as novel inhibitors of neuroinflammation." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43622.
Повний текст джерелаАнотація:
Several degenerative disorders of the central nervous system including Alzheimer’s and Parkinson’s diseases are characterized by chronic inflammation. The main contributors to this inflammation are glial cells, including microglia and astrocytes. Even though they are normally protective, disease specific stimuli can activate glial cells to start secreting neurotoxic molecules. There is no effective treatment for neurodegenerative diseases, though it is hypothesized that reducing neuroinflammation may diminish neuronal loss. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) has been linked with lower incidence of neurodegenerative disorders, though mixed results have been obtained in clinical trials of NSAIDs when these drugs are used for treatment of established disease. Gold thiol compounds, including aurothiomalate, aurothioglucose, and auranofin, comprise another class of medications effective at reducing peripheral inflammation in rheumatoid arthritis patients. Their effects on neuroinflammation are unknown. In this thesis I demonstrate that 0.1 – 5 µM auranofin, but not the other gold thiol compounds, inhibits human microglia and astrocyte-mediated neurotoxicity in vitro. The anti-neurotoxic properties of auranofin are selective; treatment with auranofin does not inhibit expression or secretion of several cytokines by glia but does upregulate heme-oxygenase (HOX)-1. Interestingly, low micromolar concentrations of auranofin directly protect neuronal cells from toxicity induced by hydrogen peroxide or stimulated glial supernatants, possibly through the upregulation of HOX-1. Lastly, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to demonstrate that auranofin reaches low micromolar concentrations in mouse brains following daily oral administration for one week. Since auranofin can protect against neuroinflammation by inhibiting glial toxicity and is directly neuroprotective, it may be useful in neurodegenerative diseases where sustained inflammation contributes to disease progression including neuronal loss.
42
Ometto, Francesca. "Validation of the italian version of the 5-item compliance questionnaire for rheumatology (i-cqr5) and a cross-sectional study on treatment adherence in rheumatoid arthritis patients." Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3421828.
Повний текст джерелаАнотація:
Background
The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely be high adherers (HA) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LA). The objective of the entire study was to validate an Italian version of I-CQR5 in rheumatoid arthritis (RA) patients. Furthermore, a cross-sectional analysis was conducted to investigate what factors are associated with high treatment adherence.
Methods
RA patients (with disease duration >1 year, undergoing treatment with ≥1 self-administered biological disease-modifying anti-rheumatic drugs (bDMARDs) or conventional synthetic DMARDs (csDMARDs), willing and capable of completing the questionnaire unaided) were enrolled in the study. The cross-cultural adaptation into Italian and validation of I-CQR5 followed standardized guidelines. The I-CQR5 was completed by patients on one occasion. Data were subjected to Partial Credit model Parametrisation (PCM) to assess the construct validity and reliability of I-CQR5. Patients who gave consent to retrieve their clinical data were included in the analysis of factors associated with high adherence to anti-rheumatic treatment. Factors included were demographic and social characteristics of the patients, and clinical and treatment information. Factors achieving a p<0.10 in univariate analysis were included in a multivariate regression analysis. Separate models were conducted in the entire cohort and in the csDMARD only- and bDMARD- treated groups.
Results
Among 604 RA patients, 401 were eligible for the analysis: 274 patients were included in the validation analysis and 328 in the cross-sectional analysis. Median age of the patients was 57 years (48-134), most were females (232, 82%), median disease duration was 12 years (7-19); 64.3% (193/300) of patients was treated with bDMARDs and 54.6% (107/300) with csDMARD treatment; 90.3% (270/299) of the patients was in low disease activity or
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remission.
Issues regarding the adaptation of CQR5 were discussed and solved by an expert committee assessment. The I-CQR5 was well understood by patients. Factor analysis and PCM confirmed the construct validity, unidimensionality and internal consistency of the I- CQR5.
HA were found to be 35.2% (109/310) of the patients: 40.2% (79/193) in patients treated with bDMARDs and 22.4% (24/107) with csDMARDs only. bDMARD treatment and employment were found to be independently associated with high adherence: OR 2.88 (1.36-6.1), p=0.006 and OR 2.36 (1.21-4.62), p=0.012 respectively. Older age, lower education level, higher prednisone daily dose, use of a csDMARD (particulary hydroxychloroquine and sulfasalazine) and higher patient-VAS were significantly more frequent in LA compared with HA but the association was not confirmed by the multivariate analysis. No independent predictors were found in the group of patients treated with csDMARDs only. Employment was also positively and significantly associated with high adherence considering patients treated with bDMARDs: OR 2.89 (1.3-6.44), p=0.009.
Conclusions
Only one third of Italian RA patients were found to be highly adherent to treatment according to the I-CQR5. Treatment with bDMARDs and employment status were the major determinants, increasing by almost 3-fold the likelihood of being adherent. Age, education level, PDN daily dose, and patient global assessment on a visual analogic scale, might contribute in explaining adherence in RA patients.Introduzione Il Compliance Questionnaire for Rheumatology (CQR5) a 5 domande permette l’identificazione dei pazienti che sono aderenti al trattamento anti-reumatico (high adherers, HA), ovvero pazienti che assumono ≥80% del trattamento correttamente, oppure poco aderenti (low adherers, LA). L’obiettivo dello studio era validare una versione italiana del CQR5 (I-CQR5) in pazienti con artrite reumatoide (AR). Inoltre è stata condotta una analisi trasversale per individuare i fattori associati ad elevata aderenza al trattamento. Metodi Sono stati arruolati pazienti con AR con una durata di malatti > 1 anno, in trattamento con ≥1 farmaco anti-reumatico biologico (bDMARD) o convenzionale (csDMARD) auto-somministrato, in grado di completare il questionario da soli e che avessero acconsentito alla partecipazione allo studio. L’adattamento cross-culturale in italiano di I-CQR5 ha seguito le linee guida stansardizzata. I-CQR5 è stato completato dai pazienti in una unica occasione. I dati sono stati analizzati con Partial Credit model Parametrisation (PCM) per valutare la validità strutturale e la reliability del I-CQR5. I pazienti che hanno acconsentito all’utilizzo dei loro dati clinici sono stati inclusi nell’analisi dei fattori associati all’aderenza al trattamento. I fattori analizzati erano: caratteristiche sociali e demografiche dei pazienti e informazioni cliniche e del trattamento. Tutti i fattori che hanno raggiunto una associazione con p<0.10 nell’analisi univariata sono stati inclusi nell’analisi di regressione multivariata. Modelli separati sono stati utilizzati per l’analisi nell’intera coorte di pazienti e nella coorte di pazienti in trattamento con soli csDMARD e nella coorte di pazienti trattati con bDMARDs. Risultati Di 604 pazienti con RA, 401 sono stati inclusi nell’analisi. Di questi 274 sono stati inclusi nell’analisi di validazione e 328 anche nello studio trasversale. L’età media dei pazienti era 57 anni (48-134), la maggior parte erano femmine (232, 82%) con durata mediana di malattia di 12 anni (7-19); 64.3% (193/300) erano trattati con bDMARDs e 54.6% (107/300) con csDMARD; 90.3% (270/299) presentavano una bassa attività di malattia o remissione. Le problematiche relative all’adattamento cross-culturale del CQR5 sono state discusse e risolte da una commissione di esperti. I-CQR5 è stato ben compreso dai pazienti. L’analisi dei fattori e la PCM hanno confermato la validità, l’unidimensionalità e la consistenza interna del I-CQR5. Gli HA erano 35.2% (109/310) dei pazienti: 40.2% (79/193) tra coloro trattati con bDMARDs e 22.4% (24/107) con soli csDMARDs. Il trattamento con bDMARD e l’impiego lavorativo sono rislutati indipendentemente associati con elevata aerenza al trattamento: OR 2.88 (1.36-6.1), p=0.006 e OR 2.36 (1.21-4.62), p=0.012 rispettivamente. Una età maggiore, un basso livello di educazione una dose maggiore giornaliera di corticosteroide e l’utilizzo di un csDMARD (in particolare idrossiclorochina e sulfasalazina) e la percezione di una maggiore attività di malattia da parte del paziente erano significativamente più frequenti tra i LA rispetto agli HA ma l’associazione non è stata confermata all’analisi multivariata. Nessun predittore di elevata aderenza al trattamento è emerso nel gruppo di pazienti trattati con soli csDMARDs. L’impiego lavorativo è risultato invece significativanente associato ad elevata aderenza al trattamento in pazienti trattati con bDMARDs: OR 2.89 (1.3-6.44), p=0.009. Conclusioni Solo un terzo di pazienti Italiani con AR sono risultati molto aderenti al trattamento misurando l’aderenza con I-CQR5. I maggiori determinanti di elevata aderenza al trattamento erano il trattamento con bDMARDs e l’impiego lavorativo aumentanto di circa 3 volte la probabilità di essere molto aderenti al trattamento.
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Garrett, Ian Ross. "Studies of the effect of metal containing drugs on acute and chronic inflammation /." Title page, table of contents and summary only, 1986. http://web4.library.adelaide.edu.au/theses/09PH/09phg2386.pdf.
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McCappin, Thomas Robertson. "The effects of adjuvant-induced arthritis and two models of renal failure on the hepatic uptake and pharmacokinetics of three drugs." Thesis, University of Aberdeen, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385477.
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Kalkan, Almina. "Diffusion, implementation and consequences of new health technology : The cases of biological drugs for rheumatoid arthritis and the Swedish national guidelines." Doctoral thesis, Linköpings universitet, Avdelningen för hälso- och sjukvårdsanalys, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-113306.
Повний текст джерелаАнотація:
Improvements in health technology raise hopes for better patient outcomes and a more efficient delivery of health care. However, the processes of diffusion and implementation of new health technology have been shown to be complicated and to pose a number of challenges for the healthcare sector. Many at tempts have been made to influence and manage the introduction and diffusion of health technology. One prominent example is the Swedish nat ional guidelines that aim at influencing both clinical and political decision - making in the health sector. The overall aim of this thesis is to describe and analyze the factors influencing the diffusion and economic consequences of the introduction of a new technology with large variations in use, and to explore the process of implementation of nationally produced guidelines as an instrument for improv ing effectiveness and equity. The empirical focus is kept on the biological drugs (bDMARDs) for rheumatoid arthritis (RA), since they implied a substantial treatment change when they were first int roduced and they are relatively costly; and on the national guidelines for cardiac care, since they were the first nat ional guidelines, hence allowing a long-term perspect ive in the exploration of their implementat ion. Paper I presents a register study that uses data from national and regional registries on healt hcare use and work disability of patients with RA and shows that there was a 32 percent increase in the total fixed cost of RA during 1990-2010, mainly after the introduct ion of bDMARDs. Paper II shows that choosing to initiate treatment with bDMARDs varied substantially among 26 rheumatologists presented with hypothetical patient cases, and that there were also disparities between rheumatologists practicing in the same clinic. Paper III presents data from the Swedish Rheumatology Quality Register covering 4010 patients with RA, and shows that when using multivariate logistic regression to adjust for patient characterist ics, disease activity and t he physician’s local context, physician preference was an import ant predict or for prescription of bDMARDs. Paper IV is a qualitative study about prescribing decisions, showing that a constellat ion of various factors and their interact ion influenced the prescribing decisions according to the 26 interviewed rheumatologists. The factors included the individual rheumatologist ’s experiences and perceptions of t he evidence, the structure of the department including responsibility for costs, peer pressure, political and administrative influences, and participat ion in clinical trials. The patient as an actor emerged as an important factor. Paper V is a longitudinal qualitat ive study exploring the responses among four Swedish county councils to the national guidelines for cardiac care through 155 interviews with politicians, administ rators and clinical managers. The results show that unilateral responses to the national guidelines within the county councils have been rare, but there have been at tempts to compromise and to at tain a balance between multiple constituents. There are examples of local information meetings, the use of the national guidelines in local healthcare programs, and performing audits with the national guidelines as a base. However, performing explicit prioritizat ion as advised in the NGCC is rarely found. Over t ime, however, a more systematic use of the national guidelines has been noted. In conclusion, the diffusion of new health technology is influenced by a wide array of factors both at individual and organizational levels, as well as their interact ion. The diffusion resulted in large economic consequences and unequal access due to variations also at clinical level. Moreover, given that healthcare decision-making is influenced by many different factors, the simple influx of evidence-based guidelines will unlikely result in automat ic implementat ion. At tempts to influence healthcare decisions need to have a systems perspect ive and to account for the interact ion of factors between different actors.
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Ho, Yee-wa Eva, and 何綺華. "Effects of Ganoderma lucidum on rheumatoid synovial fibroblasts." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29489933.
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Yue, Xiaomeng. "Medication Patterns and Comparative Effectiveness Research of Biologic Disease-modifying Antirheumatic Drugs in Children Newly Diagnosed with Juvenile Idiopathic Arthritis using Electronic Medical Records." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1613751938659097.
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Grant, Donna. "Mutations in the hypoxanthine phosphoribosyltransferase (hprt) gene in T lymphocytes from arthritis patients and in human B lymphoid cell lines exposed to nitric oxide-donating drugs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0001/MQ46576.pdf.
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Oliveira, Silvia Coimbra de. "Itinerário terapêutico de pacientes com artrite reumatoide em uso de medicamentos modificadores do curso da doença biológicos." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/6/6135/tde-05012018-095623/.
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Introdução A artrite reumatoide (AR) é uma doença crônica autoimune degenerativa, de alta prevalência e alta morbimortalidade, com difícil diagnóstico em todo o mundo. O seu pronto diagnóstico e o rápido início com medicamentos modificadores do curso da doença (MMCD) impactam de forma relevante o prognóstico do paciente. Para alguns pacientes os MMCDs sintéticos não serão eficazes e este paciente deverá receber então um MMCD biológico, medicamento este de alto custo para o paciente e o sistema de saúde. Objetivo - Explorar as trajetórias percorridas na busca por cuidado por pacientes com AR em uso de MMCD biológico no município de São Paulo. Métodos - Pesquisa qualitativa, de caráter exploratório, com orientação analítico-descritiva, mediante entrevistas semiestruturadas com questões abertas, iniciada após prévia aprovação do Comitê de Ética em Pesquisa e consentimento esclarecido dos entrevistados. Os sujeitos são pacientes em uso de MMCD biológico para tratamento de AR dispensados pelo SUS. Foi utilizada a ferramenta do itinerário terapêutico (IT) para entendimento do caminho escolhido por estes pacientes na busca por cuidado em saúde. Resultados e Discussão Entre os entrevistados, a busca de cuidado ocorreu tardiamente, normalmente sem a suspeita de que se tratasse de doença reumática degenerativa. Os primeiros profissionais acessados foram o médico clínico geral ou o ortopedista, que raras vezes investigaram com atenção os sintomas relatados para em seguida proceder o encaminhamento adequado e rápido do paciente para o reumatologista. Nos ITs descritos, os tratamentos na sua maioria são constituídos apenas pelos medicamentos, e sem a participação de outros profissionais no acompanhamento além do reumatologista. Os pacientes entrevistados chegaram até o MMCD biológico após tentativa de controle da doença com os MMCDs sintéticos, conforme descreve o protocolo de tratamento do Ministério da Saúde. Há nos ITs descritos diversos atores representantes da iniciativa privada, que apoiam e influenciam estes pacientes na escolha dos seus caminhos por cuidado de saúde, que devem ser melhor compreendidos em estudos futurosIntroduction Rheumatoid arthritis (RA) is a chronic degenerative autoimmune disease of high prevalence and with high morbidity and mortality, worldwide difficult to diagnose. Its prompt diagnosis and rapid onset with disease modifying drugs (DMARD) have a relevant impact on the patient\'s prognosis. For some patients, the synthetic DMARDs will not be effective so these patients should receive a biological DMARD - a high cost medication both to the patient and the health system. Objective - To explore the trajectories performed by patients with RA using biological DMARD in the search for care in the city of São Paulo. Methods - Qualitative research, with an exploratory character, with analytical-descriptive orientation, through semi-structured interviews with open questions, initiated after prior approval of the Committee on Ethics in Research and informed consent of the interviewees. The subjects are patients using biological DMARD to treat RA that were dispensed by SUS. The therapeutic itinerary tool (TI) was used to understand the path chosen by these patients in the search for health care. Results and Discussion Among those interviewees, the search for care occurred late, usually without the suspicion that there was a degenerative rheumatic disease. The first accessed professionals were the general practitioner or the orthopedist, who rarely ever investigated the reported symptoms with attention to direct the patient to the rheumatologist quickly. In the described TIs, the treatments are mostly composed only by the medicines, and without the participation of other professionals in the follow-up besides the rheumatologist. The patients interviewed reached the biological DMARDs after an attempt to control the disease with synthetic DMARD, as described in the Ministry of Health recommendations. There are several actors representing the private sector described in the TI\'s, who support and influence the patients in the choice of their care pathways, which should be better understood in future studies
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Xie, Fenglong. "Assessing the Comparative Effect of Tocilizumab on Risk of Cardiovascular Disease among Rheumatoid Arthritis Patients Using Claims Data| A Direct Comparison among Biologic Disease-Modifying Antirheumatic Drugs." Thesis, The University of Alabama at Birmingham, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10750692.
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Tocilizumab is a humanized monoclonal anti-body against the interleukin-6 receptor and is effective in the treatment of rheumatoid arthritis (RA). Multiple studies have observed unfavorable changes in the lipid profile of tocilizumab-treated RA patients. Few studies have compared the cardiovascular disease (CVD) risk associated with tocilizumab to other biologic disease-modifying antirheumatic drugs (bDMARDS). Due to limitations in existing studies, the real-world association of tocilizumab with CVD risk remains uncertain.
We conducted a retrospective cohort study using 2006–2015 Medicare and MarketScan claims data to assess the comparative effect of tocilizumab on CVD risk. Medicare claims data provide a unique opportunity to estimate disease burden and conduct comparative effectiveness studies with much larger sample sizes than cohorts, which require primary data collection. However, Medicare claims data lack information on cause of death. To address this limitation, we developed claims-based algorithms for identifying fatal CVD in Medicare claims data using The Reasons for Geographic and Racial Difference in Stroke (REGARDS) data linked to Medicare claims. CVD events iv and cause of death in the REGARDS study were adjudicated by two experts. Our algorithm can identify fatal CVD events with high sensitivity and specificity.
Our study confirmed that tocilizumab was not associated with increased or decreased CVD risk compared to etanercept: the hazard ratio for tocilizumab compared to etanercept was 0.91 (95%CI: 0.66, 1.25). However, unlike the clinical trial, which enrolled only high-risk patients, we extended this finding to “low CVD risk” RA patients. We also showed that tocilizumab was not associated with increased or decreased CVD risk compared to abatacept or rituximab. We further showed that tocilizumab was associated with reduced CVD risk when compared to a pooled TNFi group. This is most likely due to slightly increased CVD risk associated with infliximab.
We also conducted a retrospective cohort study using Medicare claims data to assess the effect of methotrexate on CVD risk among bDMARDS users and found that methotrexate was associated with an overall 27% (95%CI: 18–35%) reduction in CVD risk. The hazard ratio for tocilizumab concomitantly with methotrexate compared to tocilizumab only was 0.66 (95%CI: 0.40–1.09).