Comparison of Certolizumab Pegol with Other Anticytokine Agents for Treatment of Rheumatoid Arthritis: A Multiple-treatment Bayesian Metaanalysis

Abstract

Objective.To compare the clinical efficacy of certolizumab pegol (CZP) with that of other anticytokine agents indicated for the treatment of rheumatoid arthritis (RA) with identical therapeutic indication (anti-tumor necrosis factor-α, anti-interleukin 1 or 6), with the objective of determining the noninferiority of CZP.Methods.A systematic review was performed to identify randomized controlled trials that assessed the efficacy of anticytokine agents in combination with conventional disease-modifying antirheumatic drugs (DMARD) after 6 months of treatment, using the American College of Rheumatology (ACR) response criteria, in patients with RA who have shown inadequate response to DMARD including methotrexate. Indirect treatment comparisons were carried out by a multiple-treatment Bayesian random-effects metaanalysis. Data were analyzed using the Markov chain Monte Carlo simulation. Noninferiority of CZP was assessed in comparison with a predefined equivalence margin of 5%.Results.Nineteen placebo-controlled studies were identified: 14 evaluated the efficacy of 5 anti-TNF-α agents (infliximab, etanercept, adalimumab, golimumab, CZP) and 5 evaluated efficacy of 2 anti-interleukin agents (anakinra, tocilizumab). Every treatment showed significant efficacy versus placebo in individual studies. The multiple-treatment metaanalysis showed a highest OR for CZP on ACR20 response. Metaanalysis indicates that the efficacy of CZP according to ACR20 response is superior to that of infliximab, adalimumab, and anakinra, and equivalent or superior to that of etanercept, golimumab, and tocilizumab. According to ACR50 response, the efficacy of CZP is equivalent or superior to that of all other anticytokines.Conclusion.Results of this original multiple-treatment Bayesian metaanalysis indicate that certolizumab pegol is at least as efficacious as the preexisting antirheumatic anticytokine biotherapies.

A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach

“…A number of indirect comparisons have been performed to date3 4 6 8 11 38 39; this is the first such that examines the HAQ improvement incorporating baseline disease severity in a Bayesian framework. The value of MTC to evidence-based healthcare evaluations was recently highlighted 40.…”

“…Five of these studies have used a Bayesian method to combine the evidence4–6 10 11; the remaining studies used a frequentist approach. The outcomes chosen for these analyses have primarily been American College of Rheumatology (ACR) response.…”

Bayesian Inference: Statistical Gimmick or Added Value?

“…In this issue of The Journal, Launois, et al apply Bayesian methods of metaanalysis to evaluate the non-inferiority of certolizumab with other anticytokine agents for the treatment of rheumatoid arthritis 8 . Traditionally, metaanalysis is used to synthesize data from multiple studies.…”

Application of Novel Quantitative Proteomic Technologies to Identify New Serological Biomarkers in Autoimmune Diseases

“…However, it has been reported that substantial numbers of patients with autoimmune diseases still do not respond to one or more anticytokine biological agents. Among biological agents, TNF inhibitors have been extensively investigated with regard to the frequency of inadequate responders (Launois et al, 2011;Lovell et al, 2008;Maini et al, 2006;Yokota et al, 2008), because anti-TNF antibodies were the first agents approved as the therapy of RA. For example, 20~40 % of patients treated with a TNF inhibitor failed to achieve an improvement of 20 % in American College of Rheumatology criteria Rubbert-Roth and Finckh, 2009).…”