Tocilizumab as monotherapy or combination therapy for treating active rheumatoid arthritis: a meta-analysis of efficacy and safety reported in randomized controlled trials

Abstract

Background

Previous studies in patients with rheumatoid arthritis (RA) have shown that switching to tocilizumab (TCZ) monotherapy (TCZ _MONO) or combination therapy (TCZ _COMBI) with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is efficacious in reducing disease activity in patients with inadequate response to csDMARDs. However, hitherto there is no consensus on whether TCZ _MONO is as effective as TCZ _COMBI. The objective of this study was therefore to evaluate the efficacy and safety of TCZ _MONO versus add-on TCZ _COMBI and both TCZ therapies versus continuing the current csDMARD therapy, by performing a systematic review and meta-analyses.

Method

The MEDLINE, EMBASE and CENTRAL databases were searched until February 2016 for relevant randomized controlled trials (RCTs). We performed meta-analyses of Disease Activity Score in 28 joints (DAS28 < 2.6), American College of Rheumatology (ACR) 20/50/70 responses, adverse events (AEs) and serious AEs (SAEs) to compare the three different strategies, whereas a random-effect model was used for pooling relative risks (RR) and 95 % confidence intervals (CI). In addition, sensitivity analyses were performed for evaluating differences in study duration.

Results

In total, 13 RCTs were included in the meta-analysis, involving 6679 patients. When comparing both TCZ strategies, a marginally greater proportion of patients achieving DAS28 < 2.6 (RR 1.21; 95 % CI 1.09, 1.36) and ACR50 response (RR 1.14; 95 % CI 1.03, 1.26) was found in favor of the TCZ _COMBI strategy. However, the risk of SAEs was also significantly higher using this strategy (RR 1.40; 95 % CI 1.03, 1.92, p = 0.03). Pooled effect estimates showed statistical superiority of switching to either TCZ strategy compared to continuing csDMARD therapy.

Conclusions

In the management of active RA, almost similar efficacy can be expected in patients unable to tolerate csDMARDs, who switch to TCZ _MONO compared to inadequate responders switching to add-on TCZ _COMBI. Although TCZ _COMBI is marginally superior to TCZ _MONO in achieving DAS28 < 2.6 and ACR50 response, this is at the cost of an increased risk of SAEs.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-016-1108-9) contains supplementary material, which is available to authorized users.