Abstract

Introduction: Tumour-necrosis-factor (TNF) inhibitors, used to treat rheumatoid arthritis (RA), have non-specific (placebo effect) and specific effects. This meta-analysis appraises these effects within the first 3 months of treatment. Data were collected from ACR 20, 50 and 70 scores at week-24 from RA patients receiving TNF-blockers or a placebo after methotrexate (MTX) failure. Methods: A systematic literature review evaluated RCTs of TNF-blockers vs. placebo given to patients after MTX failure (10 mg/week during 6 months), published until October 2015. RA patients were naive to biotherapies. Results: Twenty-two RCTs (out of 1,388) were evaluated: six studied infliximab, five etanercept, four adalimumab, three certolizumab and four golimumab. Thirteen RCTs were available for the ACR 20 score at week-24. The overall placebo effect was 24.7% (CI95% [0.192;0.301] p = 0), the adalimumab one was 26.7% ((CI95% [0.161;0.373]) p = 0.001), certolizumab 16.4% ((CI95% [0.068;0.26]) p = 0), and infliximab 31.9% ((CI95% [0.154;0.485]) p = 0.001). Subgroup analyses showed the i.v. route generated a 31.90% placebo effect vs. 23.30% via the subcutaneous route (95%CI [0.154;0.485] p = 0.001). The placebo ACR-50 response was 10.90% ((CI95% [0.074;0.144]) p = 0) for 14 RCTs: only adalimumab was significant (15.40%, (CI95% [0.026;0.281]) p = 0). The ACR-70 placebo effect was 3.40% (95% (CI [0.019; 0.049]) p = 0) in 13 studies (NS). Conclusions: Even though TNF-blockers had greater efficacy, placebo effect should be considered. Indeed, it is estimated at ~20% even treatment failure. Adalimumab, certolizumab and infliximab had higher placebo effects, as did the i.v route. The greater the stringency of ACR criteria, the more the placebo effect was decreased.

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