Objective: To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom.
Methods: A systematic literature search identified 11 individual studies investigating the efficacy of abatacept, infliximab, adalimumab, etanercept, certolizumab pegol, and golimumab in adult patients with RA that did not respond to MTX. The clinical trials included in this analysis were similar in trial design, baseline patient characteristics, and background therapy (i.e., MTX). The key clinical endpoints of interest were the Health Assessment Questionnaire (HAQ) change from baseline (CFB) and the American College of Rheumatology (ACR) responses at 6 months (24-28 weeks). Results were analyzed using Bayesian network metaanalysis methods, and were expressed as differences in HAQ CFB and ACR20/50/70 relative risks, with 95% credible limits (CrL).
Results: Analysis of HAQ CFB at 6 months showed that abatacept is more efficacious than placebo [mean difference in HAQ CFB: -0.30 (95% CrL -0.42; -0.16)] and comparable to all other biologic agents, in patients receiving MTX as background treatment. Abatacept is also expected to result in a higher proportion of ACR responders compared to placebo, with relative risks ranging from 1.90 (95% CrL 1.24; 2.57) for ACR20 to 3.72 (95% CrL 1.50; 10.52) for ACR70, and to result in comparable proportions of ACR responders as other biologic agents, at 6 months.
Conclusion: Abatacept is expected to result in improvement in functional status comparable to other recommended biologic agents in patients with RA who are unresponsive to MTX in the UK.
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http://dx.doi.org/10.3899/jrheum.111345 | DOI Listing |
Mol Biol Cell
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Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
β-tubulin isotypes exhibit similar sequences but different activities, suggesting that limited sequence divergence is functionally important. We investigated this hypothesis for TUBB3/β3, a β-tubulin linked to aggressive cancers and chemoresistance in humans. We created mutant yeast strains with β-tubulin alleles that mimic variant residues in β3 and find that residues at the lateral interface are sufficient to alter microtubule dynamics and response to microtubule targeting agents.
View Article and Find Full Text PDFMetab Brain Dis
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School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
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View Article and Find Full Text PDFPlanta
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Department of Vegetable and Medicinal Plants, Institute of Horticulture Sciences, Warsaw University of Life Sciences, 159 Nowoursynowska Street, 02-776, Warsaw, Poland.
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J Membr Biol
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Cancer is a leading cause of death worldwide and its treatment is hampered by the lack of specificity and side effects of current drugs. Cardiotonic steroids (CTS) interact with Na/K-ATPase (NKA) and induce antineoplastic effects, but their narrow therapeutic window is key limiting factor. The synthesis of digitoxigenin derivatives with glycosidic unit modifications is a promising approach to develop more selective and effective antitumor agents.
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