Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate: a network meta-analysis

Abstract

IntroductionThe goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR).MethodsA systematic literature review identified controlled trials investigating the efficacy of abatacept (three studies), etanercept (two studies), infliximab (two), adalimumab (two), certolizumab pegol (two) ritixumab (three), and tocilizumab (two) in MTX-IR patients with RA. The clinical trials included in this analysis were similar with respect to trial design, baseline patient characteristics and background therapy (MTX). The key clinical endpoints of interest were HAQ CFB, ACR-50 and DAS28 < 2.6 measured at 24 and 52 weeks. The results were analysed using network meta-analysis methods that enabled calculation of an estimate for expected relative effect of comparative treatments. Analysis results were expressed as the difference in HAQ CFB score and odds ratio (OR) of achieving an ACR-50 and DAS28 response and associated 95% credible intervals (CrI).ResultsThe analysis of HAQ CFB at 24 weeks and 52 weeks showed that abatacept in combination with MTX is expected to be more efficacious than MTX monotherapy and is expected to show a comparable efficacy relative to other biologic DMARDs in combination with MTX. Further, abatacept showed comparable ACR-50 and DAS28 < 2.6 response rates with other biologic DMARDs at 24 and 52 weeks, except for ACR-50 compared to certolizumab pegol at 52 weeks and for DAS28 < 2.6 compared to tocilizumab at 24 weeks. Sensitivity analyses confirmed the robustness of the findings.ConclusionsAbatacept in combination with MTX is expected to result in a comparable change from baseline in HAQ score and comparable ACR-50 and DAS28 < 2.6 response rates in MTX-IR patients compared to other approved biologic agents.

Effectiveness of abatacept for patients with Sjögren’s syndrome associated with rheumatoid arthritis. An open label, multicenter, one-year, prospective study: ROSE (Rheumatoid Arthritis with Orencia Trial toward Sjögren’s syndrome Endocrinopathy) trial

“…Especially, in 29 bio-naïve patients, the remission rate was 37.9% (11/29 patients) at 52 weeks, compared with 14.3% in 7 bio-switch patients. A previous meta-analysis study that examined the effectiveness of abatacept combined with MTX against active RA, reported that the remission rate, defined by DAS28-ESR52.6, was 40.2% (95% confidence interval: 10.4-80.3%) [25]. Thus, the remission rate in our study seems to be comparable with that of previous studies on similar RA patients.…”

Inflammatory signaling induced bone loss

“…Subsequently, the use of additional therapeutic agents targeting alternate cytokines, including IL-6 in RA, as well as IL-23 or IL-17 in the SpAs, represent additional "activation nodes" involving these cytokines [24][25][26][27][28][29] . Therapies targeting T cell co-stimulatory effector pathways also have been shown to be effective in controlling synovial inflammation and joint damage in RA 30 . More recently, therapies targeting B cells also have shown efficacy, providing evidence of the importance of both T and B cells in RA pathogenesis 31 .…”

Why the findings of published multiple treatment comparison meta-analyses of biologic treatments for rheumatoid arthritis are different: an overview of recurrent methodological shortcomings

“…RA is a complex area with many clinical factors potentially influencing the relative efficacy and safety of the individual bDMARDs (eg, treatment and response history, concomitant use of MTX, dosing of the administered bDMARD, and pretreatment disease duration) 8 10 11 15 16 18. Similarly, MTC is a relatively new statistical approach that has little established guidance on how to perform a gold-standard analysis 17.…”