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

J Clin Gastroenterol. 2017 May/Jun;51(5):394-401. doi: 10.1097/MCG.0000000000000758.

Abstract

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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adrenal Cortex Hormones / adverse effects*
  • Biological Products / adverse effects*
  • Epstein-Barr Virus Infections / chemically induced*
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / virology
  • Gastrointestinal Agents / adverse effects*
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / pathogenicity
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / adverse effects*
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Opportunistic Infections / chemically induced*
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / immunology
  • Opportunistic Infections / virology
  • Purines / adverse effects*
  • Risk Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology
  • Virus Activation / drug effects*

Substances

  • Adrenal Cortex Hormones
  • Biological Products
  • Gastrointestinal Agents
  • Immunosuppressive Agents
  • Purines
  • Tumor Necrosis Factor-alpha