Infectious Complications of TNF-α Inhibitor Monotherapy versus Combination erapy with Immunomodulators in In ammatory Bowel Disease: Analysis of the Food and Drug Administration Adverse Event Reporting System*

Background & Aim: Incremental increase in the risk of serious infections with combinations of tumor necrosis factor-alpha (TNF-α) inhibitors and immunomodulators compared to monotherapy with these agents in in ammatory bowel disease (IBD) is unclear. Our aim was to analyze whether there is such an incremental increase in the odds of serious infections. Methods: e FDA Adverse Event Reporting System (2003 June 2011) was queried for ‘Primary Suspect’ reports of various infections with TNF-α inhibitors, systemic corticosteroids and immunomodulators with usage indication of IBD. Odds ratios (ORs) were calculated for baseline odds of infections as well as serious infections (requiring hospitalization and/or death) with monotherapy and combination therapy (compared to 5-Aminosalicylates) as well as incremental increase in odds for dual or triple combination therapy (compared to monotherapy or dual combination therapy respectively) using Fisher’s exact test with SPSS 20 (IBM Co. Armonk, NY, USA). Results: TNF-α inhibitor (OR 1.95; CI, 1.06-3.59) and immunomodulator (OR 9.99; CI, 1.28-78.16) monotherapy as well as in combination augmented baseline odds of serious infection for IBD patients. No incremental increase in the odds with combination therapy was seen when an immunomodulator was added to a TNF-α inhibitor (OR 0.37; CI, 0.05-2.80) and when both were used with a systemic corticosteroid (OR 0.91; CI, 0.50-1.66). Variations in these were seen for the individual infection subtypes. Conclusions: TNF-α inhibitor and immunomodulator monotherapy increase the baseline odds of acquiring a serious infection. Combination therapy with these drugs does not further increase the odds of serious infections compared to monotherapy.