Comparative efficacy of biologics as monotherapy and in combination with methotrexate on patient reported outcomes (PROs) in rheumatoid arthritis patients with an inadequate response to conventional DMARDs – a systematic review and network meta-analysis

Abstract

ObjectiveTo compare biologics as monotherapy or in combination with methotrexate (MTX) in terms of patient reported outcomes (PROs) in RA patients with an inadequate response to conventional DMARDs (DMARD-IR).MethodsWith a systematic literature review 17 RCTs were identified that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, abatacept, anakinra or tocilizumab. Treatment effects in terms of pain (0-100 mm), patient’s global assessment of disease activity (PGA; 0-100 mm), Health Assessment-Questionnaire (HAQ) disability index (DI; 0–3), and the physical component summary (PCS) of the SF36 Health Survey (0–100) at 24 weeks were combined by means of Bayesian network meta-analyses.ResultsWith tocilizumab monotherapy, greater improvements in pain (difference = -11.1; (95% Credible Interval -21.3, -0.1)) and PGA (-10.3 (-20.4, 0.8)) were observed than with aTNF monotherapy. Tocilizumab was at least as efficacious as aTNF in HAQ-DI improvements (-0.16; (-0.37, 0.05)). aTNF + MTX (-17.9 (-23.1, -13.0) & -19.1 (-24.2, -14.4)), abatacept + MTX (-23.0 (-47.3, 1. 5) & -13.6 (-28.4, 2.0)) and tocilizumab + MTX (-16.0 (-26.3, -6.3) & -15.1 (-25.1, -5.7)) showed comparable reductions in pain and PGA relative to MTX. Efficacy of anakinra + MTX was much smaller as compared to other biologics. The greatest improvements in HAQ-DI relative to MTX were observed with aTNF + MTX (-0.30 (-0.37, -0.22)) and tocilizumab + MTX (-0.27 (-0.42, -0.12)), followed by abatacept + MTX (-0.21 (-0.37, -0.05)) and anakinra + MTX (-0.11 (-0.26, 0.05)). The improvements in SF36-PCS with abatacept + MTX, aTNF + MTX and tocilizumab + MTX were comparable. There is a >90% probability that aTNF + MTX results in a greater improvement in pain (-12.4), PGA (-16.1) and HAQ-DI (-0.21) than aTNF as monotherapy. Efficacy of tocilizumab + MTX showed comparable improvements in PROs as tocilizumab monotherapy.ConclusionsBased on a network meta-analysis involving indirect comparison of trial findings, the following observations were made for DMARD-IR patients. In monotherapy, tocilizumab was associated with a greater improvement in pain and self-reported disease activity than aTNF, and was at least as efficacious regarding functional ability. The improvements in PROs with aTNF, abatacept and tocilizumab in combination with MTX were comparable. Improvements in PROs with tocilizumab as monotherapy were similar to that of tocilizumab + MTX, whereas aTNF as monotherapy was likely to be less efficacious than aTNF + MTX.

Frequency and Factors Associated with Biologic Monotherapy in Patients with Rheumatoid Arthritis; Experience from an Argentine Center

“…Notwithstanding, we know that adalimumab, etanercept and certolizumab are approved for use as monotherapy, in spite of not being so by international guidelines [35]. Even though, this data is supported by multiple pivotal anti-TNF clinical studies, some metaanalysis have shown that overall anti-TNF have an 87% and 90% probability of achieving ACR 20 and 50 respectively, with an 2.4 OR with regards to monotherapy [36].…”

Pain in systemic inflammatory rheumatic diseases

“…It may be due to active inflammation or joint damage arising from previous inflammation and tissue destruction, but it is frequently multifactorial in origin and has both central and peripheral components [34]. Treatment with DMARDs and NSAIDs reduces the inflammatory pain symptoms [35], although the fact that many patients continue to experience moderate pain [36,37] suggests the existence of a non-inflammatory component with a different aetiology and/or alterations in central pain regulation mechanisms [38].…”

Is it the time to rethink clinical decision-making strategies? From a single clinical outcome evaluation to a Clinical Multi-criteria Decision Assessment (CMDA)

“…Some network meta-analysis (NMA) have been performed to compare the clinical efficacy of EU licensed-dose bDMARDs for the treatment of RA patients after failure on cDMARDs [44][45][46][47]. Efficacy was measured using American College of Rheumatology (ACR) response end points from RCTs.…”