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

Research output: Contribution to journalReview articlepeer-review

Original languageEnglish
Pages (from-to)4450-4462
Number of pages13
Issue number10
Early online date18 May 2021
E-pub ahead of print18 May 2021
Published1 Oct 2021

Bibliographical note

Funding Information: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. However, M.D.R. receives funding from the National Institute for Health Research, V.A. receives funding from the National Institute for Health Research, and B.D.C. receives funding from Innovate UK. Publisher Copyright: © 2021 The Author(s) 2021.

King's Authors


Objectives: To evaluate the safety of treatment strategies in patients with early RA. Methods: Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomized controlled trials (RCTs) of licensed treatments conducted on completely naïve or MTX-naïve RA patients were included. Long-term extension studies, post-hoc and pooled analyses and RCTs with no comparator arm 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 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 with MTX monotherapy, rate ratio 1.39 (95% CI: 1.12, 1.73). Biologic monotherapy rates were higher than those for 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 revealed the different risk profiles for various early RA treatment strategies. Observed differences were overall small, and in contrast to the findings of established RA studies, steroid-based regimens did not emerge as more harmful.

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