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Bilal J, Berlinberg A, Riaz IB, et al. Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019;2(10):e1913102. doi:10.1001/jamanetworkopen.2019.13102
What is the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with interleukin inhibitors?
In this systematic review and meta-analysis of 74 randomized clinical trials comprising 29 214 patients, pooled results suggest that risk of serious infections, opportunistic infections, and cancer is increased in patients with rheumatologic diseases who are treated with interleukin inhibitors compared with placebo.
This analysis suggests estimates of risk for infections and cancer associated with the use of interleukin inhibitors that can inform shared decision-making when patients and clinicians are contemplating the use of interleukin inhibitors for rheumatologic diseases.
The safety profile of interleukin (IL) inhibitors is not well established.
To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors.
Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus were searched (inception to November 30, 2018).
Randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic diseases and reported safety data were included in the analyses.
Data Extraction and Synthesis
This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two investigators independently extracted study data and assessed risk of bias and certainty in the evidence. Fixed-effects meta-analysis was conducted to pool odds ratios (ORs) for serious infections, opportunistic infections, and cancers for IL inhibitors vs placebo.
Main Outcomes and Measures
The outcomes of interest were the number of serious infections, opportunistic infections, and cancers in individuals receiving IL inhibitor therapies compared with placebo.
In this meta-analysis, 74 studies comprising 29 214 patients (24 236 patients for serious infections, 9998 for opportunistic infections, and 21 065 for cancer [number of patients overlaps for each outcome]) were included. Patients receiving IL inhibitors had a higher risk of serious infections (OR, 1.97; 95% CI, 1.58-2.44; P < .001, I2 = 0%; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P = .03, I2 = 0%; moderate certainty), and cancer (OR, 1.49; 95% CI, 1.04-2.16; P = .03, I2 = 11%; moderate certainty).
Conclusions and Relevance
The risk of serious infections, opportunistic infections, and cancer appears to be increased in patients with rheumatologic diseases who are treated with IL inhibitors compared with placebo.
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