Tumor Necrosis Factor-Alpha Blockers do not Augment the Risk of Viral Infection in Inflammatory Bowel Disease (IBD): A Review of the Food and Drug Administration Adverse Event Reporting System (FDA AERS)

Abstract

Purpose: Tumor Necrosis Factor-alpha (TNF-α) blockers have been reported to cause hepatitis B reactivation as well as an increased risk of herpes zoster. We sought to clarify the risk of viral infections with TNF-α blockers compared to other approved drugs in IBD. Methods: A total of 2,562,390 files for the period 2003- June 2011 from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) were downloaded and analyzed using SPSS 20 (IBM Co. Armonk, NY, USA). Files were queried for viral infection reactions terms from the Medical Dictionary for Regulatory Activities (MedDRA) such as “Meningitis enteroviral”, “Cytomegalovirus viraemia”, “Epstein-Barr viraemia” for the three approved TNF-α blockers in IBD, as well as immunomodulators, systemicuse corticosteroids and control medications (5-Aminosalicylic acid) and all the trade names. Reports were selected where indication for usage was IBD, further analyzed for concomitant medications from the study drug classes. Additionally, four reaction terms -“syncope”, “hernia”, “deafness” and “vertigo” were selected as control reactions, predefined to have no association with the interest or control drugs. Odds ratios (ORs) for the risk of viral infections with TNF-α blockers, immunomodulators or corticosteroids as well as their combinations were calculated using Fisher's exact test using SPSS 20. Results: A total of 1,664 primary suspect reports of viral infections were reported with TNF-α blockers in IBD. The influenza virus was the most commonly reported virus type (593 reports) (Figure 1). Classifying by organ system, respiratory illness (627 reports) were most commonly reported. ORs for viral infections were non-significant for use of TNF-α blockers (OR 1.062, confidence interval (CI) 0.33-3.03), steroids (OR 0.52, CI 0.13-2.01) or immunomodulators alone (OR 5.4, CI 0.59-49.91) or TNF-α blockers in combination with either steroids (OR 0.95, CI 0.30-2.98) or immunomodulators (1.14, CI 0.37-3.51) or all 3 combined in IBD (OR 1.01, CI 0.32-3.19).Figure 1: Viral infection reports with TNF-α blockers by virus type.Conclusion: TNF-α blockers used alone or in combination with immunomodulators and/or corticosteroids do not appear to be associated with increased risk for viral infections in IBD.