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Corticosteroids and Thiopurines, But Not Tumor Necrosis Factor Antagonists, are Associated With Cytomegalovirus Reactivation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Shukla, Tushar MD; Singh, Siddharth MD, MS; Tandon, Parul DO; McCurdy, Jeffrey D. MD, PhD

Journal of Clinical Gastroenterology: May/June 2017 - Volume 51 - Issue 5 - p 394–401
doi: 10.1097/MCG.0000000000000758
Clinical Review

Background: The association between cytomegalovirus (CMV) reactivation and individual immunosuppressive agents in inflammatory bowel disease (IBD) has not been clearly defined. Therefore, we performed a systematic review and meta-analysis to assess this association.

Methods: Multiple electronic databases were searched systematically through July 2015 for observational studies reporting CMV reactivation (based on serum-based or tissue-based tests) in IBD patients stratified by medication exposure. We estimated summary odds ratios (ORs) and 95% confidence intervals (CI) using random-effects model. Study quality was assessed using the Newcastle-Ottawa scale.

Results: Sixteen observational studies were identified. As compared with nonexposed patients, exposure to corticosteroids (CS) (12 studies, 1180 patients, 52.3% exposed; OR, 2.05; 95% CI, 1.40-2.99) and thiopurines (14 studies, 1273 patients, 24.1% exposed; OR, 1.56; 95% CI, 1.01-2.39) was associated with increased risk of CMV reactivation. In contrast, as compared with patients not exposed to tumor necrosis factor (TNF) antagonists, exposure to TNF antagonists was not associated with an increased risk of CMV reactivation (7 studies, 818 patients, 18.5% exposed; OR, 1.44; 95% CI, 0.93-2.24). The results remained stable for CS and thiopurines when the analysis was limited to hospitalized patients, and by a tissue-based diagnosis. Studies were limited in the ability to assess the impact of concomitant immunosuppressive therapy, duration of medication exposure, and disease severity.

Conclusions: On the basis of 16 observational studies, exposure to CS or thiopurines, but not TNF antagonists, was associated with an increased risk of CMV reactivation in IBD patients.

Supplemental Digital Content is available in the text.

*Division of Gastroenterology and Hepatology, The Ottawa Hospital, Ottawa, ON, Canada

Division of Gastroenterology, University of California San Diego, La Jolla, CA

T.S.: data acquisition, data analysis, drafting of the manuscript; P.T.: data acquisition; S.S.: data analysis, critical revision of the manuscript; J.D.M.: study concept design, data acquisition, data analysis, drafting of the manuscript.

The authors declare that they have nothing to disclose.

Address correspondence to: Jeffrey D. McCurdy, MD, PhD, Division of Gastroenterology and Hepatology, The Ottawa Hospital, 737 Parkdale Ave., Suite 468, Ottawa, ON, Canada K1Y 1J8 (e-mail:

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