Effect of Tumor Necrosis Factor-α Inhibitors on Drug-Induced Pancreatitis in Inflammatory Bowel Disease

Background:Mesalamine and thiopurines (6-mercaptopurine and azathioprine) have been shown to increase the risk of developing acute pancreatitis in inflammatory bowel disease (IBD) patients. Tumor necrosis factor-alpha (TNF-alpha) inhibitors have been shown to protect against pancreatitis in animal models. Objective: To determine the risk of pancreatitis when comparing thiopurine monotherapy, mesalamine monotherapy, and thiopurine and mesalamine dual therapy to identical treatments but with the addition of a TNF-alpha inhibitor. Methods: Using a case-control design, the Food and Drug Administration Adverse Event Reporting System was queried for cases of pancreatitis and control reactions in IBD patients on a thiopurine or mesalamine. The proportional reporting ratio method was used to compare the different therapy regimens with the same regimen combined with a TNF-alpha inhibitor. Results: In all, 549 cases and controls were identified. When comparing thiopurine monotherapy with thiopurines combined with a TNF-alpha inhibitor, the odds of pancreatitis were lower in those on combination therapy (odds ratio [OR] = 0.04; 95% Cl = 0.01-0.12). A similar trend was seen when comparing mesalamine monotherapy to mesalamine combined with a TNF-alpha inhibitor (OR = 0.08; 95% Cl = 0.04-0.14) and when comparing those on both a thiopurine and mesalamine with those on all 3 therapies (OR = 0.04; 95% Cl = 0.01-0.16). Conclusions: Combination therapy with TNF-alpha inhibitors appears to be associated with a lower risk of pancreatitis in IBD patients on mesalamine, thiopurines, or a combination of both. Physicians should consider using TNF-alpha inhibitors in those with the greatest risk of pancreatitis, although prospective studies are needed.