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

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.