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

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To evaluate the safety of treatment strategies in patients with early rheumatoid arthritis (RA).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-naïve or methotrexate (MTX)-naïve 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).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.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.

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Authors: Maryam A Adas, Victoria B Allen, Mark Yates, Katie Bechman, Benjamin D Clarke, Mark D Russell, Andrew I Rutherford, Andrew P Cope, Sam Norton, James B Galloway


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