A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis

Objective. We examined how combination DMARD therapies and TNF inhibitors therapies plus MTX (TNF/MTX) affect clinical and radiological outcomes compared with MTX monotherapy in early RA. Methods. We systematically searched EMBASE, PubMed and Ovid Medline for randomized controlled trials (RCTs) of combination therapy in early RA. We evaluated ACR responses, withdrawals for inefficacy and toxicity, HAQ and radiographic progression. Meta-analysis using Review Manager evaluated random effects odds ratios (ORs) and random effects weighted mean differences (WMDs) between treatments. Results. A preliminary search identified 2029 citations; 15 were relevant RCTs (4200 randomized patients). Patients with active disease were enrolled. Compared with MTX monotherapy, both combination DMARDs and TNF/MTX increased ACR20-70 responses (OR 1.64-2.02 and 2.03-2.30, respectively), reduced withdrawals for inefficacy (OR 0.52 and 0.29), reduced HAQ (WMD -0.17 and -0.16) and reduced annual X-ray progression (WMD -1.20 and -0.84%). DMARD combinations increased withdrawals for toxicity (OR 2.69; there was no difference with TNF/MTX). The only head-to-head RCT showed comparable efficacy for combination DMARDs and TNF/MTX combinations. Conclusions. In early active RA, both combination DMARDs and TNF/MTX are more effective than MTX monotherapy. DMARD and TNF/MTX combinations had equal efficacy on ACR response, withdrawals for inefficacy, disability and erosive progression. There is an apparent advantage for TNF/MTX combinations in the effect on toxicity with fewer consequent patients. We conclude that there is strong evidence in favour of combination treatment for RA but there is still uncertainty about which regimen is preferable.