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Meta-Analysis
. 2019 Oct 2;2(10):e1913102.
doi: 10.1001/jamanetworkopen.2019.13102.

Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors: A Systematic Review and Meta-analysis

Jawad Bilal  1 , Adam Berlinberg  2 , Irbaz Bin Riaz  3 , Warda Faridi  4 , Sandipan Bhattacharjee  5 , Gilbert Ortega  6 , Mohammad H Murad  7 , Zhen Wang  7 , Larry J Prokop  8 , Abdullah A Alhifany  9 , C Kent Kwoh  1   10
Affiliations
Meta-Analysis

Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors: A Systematic Review and Meta-analysis

Jawad Bilal et al. JAMA Netw Open. .

Erratum in

  • Error in Figure 2, Figure 3, and Results.
    [No authors listed] [No authors listed] JAMA Netw Open. 2020 Apr 1;3(4):e205507. doi: 10.1001/jamanetworkopen.2020.5507. JAMA Netw Open. 2020. PMID: 32275317 Free PMC article. No abstract available.

Abstract

Importance: The safety profile of interleukin (IL) inhibitors is not well established.

Objective: To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors.

Data sources: 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).

Study selection: 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.

Results: 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, 1.52; 95% CI, 1.05-2.19; 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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kwoh reported receiving grants and personal fees from EMD Serono, grants from Pfizer, and personal fees from Astellas, Regulus, Kolon Tissue Gene, Taiwan Liposome Company, Fidia, Thuasne, GlaxoSmithKline, Regeneron, and Express Scripts outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Flow Diagram
RCT indicates randomized clinical trial.
Figure 2.
Figure 2.. Risk of Serious Infections
Size of box indicates relative weights of the studies. IL indicates interleukin; M-H, Mantel-Haenszel; and OR, odds ratio.
Figure 3.
Figure 3.. Risk of Cancer
Size of box indicates relative weights of the studies. IL indicates interleukin; M-H, Mantel-Haenszel; and OR, odds ratio.
See this image and copyright information in PMC

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