Safety of combination therapies in early rheumatoid arthritis: a systematic comparison between antirheumatic drugs and TNF inhibitors with methotrexate

We evaluated the frequency and type of adverse effects associated with combination disease-modifying antirheumatic drugs and TNF inhibitors combined with methotrexate (MTX) compared with MTX monotherapy by systematically reviewing trials in early rheumatoid arthritis. We identified 15 relevant trials by searching EMBASE, Medline and Cochrane databases (1960 to March 2010). Combination therapy gave more withdrawals for toxicity than MTX monotherapy. There was more nausea with combination disease-modifying antirheumatic drugs and more serious adverse events with TNF inhibitors combined with MTX. The total numbers of adverse events, serious infections, malignancies and deaths were similar with combination therapy and monotherapy. However, the short follow-up period may have been inadequate to detect new malignancies. Events in individual systems were uncommon and did not show major differences between groups. We conclude there is no evidence that intensive therapy in early rheumatoid arthritis causes unaccep...