Biologic DMARDs and targeted synthetic DMARDs and the risk of all-cause mortality in rheumatoid arthritis: A systematic review and meta-analysis

Background: The aim of this study was to perform a meta-analysis to compare the risk of all-cause mortality between biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and non-b/tsDMARDs involving patients with rheumatoid arthritis (RA). Methods: We performed a systematic review of articles published up to August 2021 using electronic databases. We included studies that reported all-cause mortality in RA patients and compared b/tsDMARDs and non-b/tsDMARDs. Results: We included a total of 77 studies involving 64,428 patients. These comprised 44,227 patients treated with b/tsDMARDs and 20,201 treated with non-b/tsDMARDs. The occurrence of all-cause mortality was the primary outcome. The risk of all-cause mortality between the 2 treatments was not significantly different (relative risk = 1.08; 95% confidence interval = 0.98-1.19). However, subgroup analyses showed significant increase in risks of mortality in anti-TNFs users with RA compared with non-b/tsDMARDs (relative risk = 1.47, 95% confidence interval = 1.02-2.12). No significant differences were found after subgroup analyses based on other molecules involved and study duration. Conclusion: In comparison with non-b/tsDMARDs, our results suggest that antitumor necrosis factor therapy is associated with observed increased risks of mortality and further investigation is needed.