First-line biologic and targeted synthetic DMARDs versus methotrexate in early rheumatoid arthritis: a meta-analysis of remission outcomes

Abstract Objectives To evaluate initial therapy with biologic and targeted synthetic DMARDs (b/tsDMARDs), compared with methotrexate, in patients with early RA. Methods We systematically reviewed and meta-analysed randomized-controlled trials comparing initial b/tsDMARDs, combined with methotrexate or as monotherapy, against methotrexate in methotrexate-naïve adults with early RA. Pairwise and network meta-analysis were performed to compare DAS28 remission attainment, with the primary analysis at 6 months and secondary analyses at 3 and 12 months. Secondary outcomes included ACR50 response and CDAI remission. Results Twenty-nine trials (13 387 participants) were included. Compared with methotrexate alone, initial b/tsDMARDs plus methotrexate significantly increased DAS28 remission at 6 months (risk ratio [RR] 1.62; 95% CI: 1.39, 1.89), 3 months (RR 1.95; 1.47, 2.57) and 12 months (RR 1.54; 1.39, 1.71), with benefits also observed for CDAI remission and ACR50 response. In network meta-analysis, all b/tsDMARD classes combined with methotrexate had higher remission rates than methotrexate alone. The benefits of b/tsDMARDs plus methotrexate were greater in studies with higher baseline disease activity and a greater proportion of rheumatoid factor-positive participants. As monotherapy, b/tsDMARDs increased DAS28 remission attainment compared with methotrexate at 6 months (RR 1.81; 1.42, 2.31), 3 months (RR 1.92; 1.31, 2.83) and 12 months (RR 1.46; 1.25, 1.71); however, at individual class level, significantly higher remission rates were observed only with tocilizumab and Janus kinase (JAK) inhibitor monotherapy. Conclusion Initial therapy with b/tsDMARDs in combination with methotrexate is associated with higher remission rates than methotrexate alone in patients with early RA. As monotherapy, higher remission rates were observed for JAK inhibitors and tocilizumab.