A systematic review and network meta-analysis on the safety of early interventional treatments in rheumatoid arthritis.

Objectives To evaluate the safety of treatment strategies in patients with early rheumatoid arthritis (RA). Methods Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomised controlled trials (RCTs) of licensed treatments conducted on completely-naive or methotrexate (MTX)-naive RA were included. RCTs with no comparator arm, long-term extension studies, post-hoc and pooled analyses were excluded. Serious adverse events, serious infections and non-serious adverse events were extracted from all RCTs, and event rates in intervention and comparator arms were compared using a meta-analysis and network meta-analysis (NMA). Results From an initial search of 3423 studies, 20 were included. Involving 9202 patients. From the meta-analysis, the pooled incidence rates per 1000 patient years for serious adverse events were 69.8 (95% CI: 64.9-74.8), serious infections 18.9 (95% CI: 16.2-21.6) and non-serious adverse events 1048.2 (95% CI: 1027.5-1068.9). NMA showed that serious adverse event rates were higher with biologic monotherapy than MTX monotherapy, rate ratio 1.39 (95% CI: 1.12-1.73); biologic monotherapy rates were higher than MTX and steroid therapy, rate ratio 3.22 (95% CI: 1.47-7.07). Biologic monotherapy had a higher adverse event rate than biologic combination therapy, rate ratio 1.26 (95% CI: 1.02-1.54). NMA showed no significant difference between strategies with respect to serious infections and non-serious adverse events rates. Conclusion The study demonstrated the different risk profiles for early RA treatment strategies. Observed differences were overall small, and in contrast to established RA studies, steroid-based regimens did not emerge as more harmful.