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

Jawad Bilal, Adam Berlinberg, Irbaz Bin Riaz, Warda Faridi, Sandipan Bhattacharjee, Gilbert Ortega, Mohammad H. Murad, Zhen Wang, Larry J. Prokop, Abdullah A. Alhifany, C. Kent Kwoh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)e1913102
JournalJAMA Network Open
Volume2
Issue number10
DOIs
StatePublished - Oct 2 2019

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Interleukins
Opportunistic Infections
Meta-Analysis
Infection
Odds Ratio
Placebos
Neoplasms
MEDLINE
Safety
Information Storage and Retrieval
Rheumatic Diseases
Randomized Controlled Trials
Research Personnel
Outcome Assessment (Health Care)
Databases
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors : A Systematic Review and Meta-analysis. / Bilal, Jawad; Berlinberg, Adam; Riaz, Irbaz Bin; Faridi, Warda; Bhattacharjee, Sandipan; Ortega, Gilbert; Murad, Mohammad H.; Wang, Zhen; Prokop, Larry J.; Alhifany, Abdullah A.; Kwoh, C. Kent.

In: JAMA Network Open, Vol. 2, No. 10, 02.10.2019, p. e1913102.

Research output: Contribution to journalArticle

Bilal, J, Berlinberg, A, Riaz, IB, Faridi, W, Bhattacharjee, S, Ortega, G, Murad, MH, Wang, Z, Prokop, LJ, Alhifany, AA & Kwoh, CK 2019, 'Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors: A Systematic Review and Meta-analysis', JAMA Network Open, vol. 2, no. 10, pp. e1913102. https://doi.org/10.1001/jamanetworkopen.2019.13102
Bilal, Jawad ; Berlinberg, Adam ; Riaz, Irbaz Bin ; Faridi, Warda ; Bhattacharjee, Sandipan ; Ortega, Gilbert ; Murad, Mohammad H. ; Wang, Zhen ; Prokop, Larry J. ; Alhifany, Abdullah A. ; Kwoh, C. Kent. / Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors : A Systematic Review and Meta-analysis. In: JAMA Network Open. 2019 ; Vol. 2, No. 10. pp. e1913102.
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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.",
author = "Jawad Bilal and Adam Berlinberg and Riaz, {Irbaz Bin} and Warda Faridi and Sandipan Bhattacharjee and Gilbert Ortega and Murad, {Mohammad H.} and Zhen Wang and Prokop, {Larry J.} and Alhifany, {Abdullah A.} and Kwoh, {C. Kent}",
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AU - Faridi, Warda

AU - Bhattacharjee, Sandipan

AU - Ortega, Gilbert

AU - Murad, Mohammad H.

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AU - Alhifany, Abdullah A.

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N2 - 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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