Ischemic Colitis During Treatment with Tumor Necrosis Factor Alpha Inhibitors in Rheumatoid Arthritis

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Purpose: Tumor necrosis factor alpha (TNF-α) inhibitors are approved for the treatment and maintenance of rheumatoid arthritis (RA). Immunosuppression has been shown to induce ischemic colitis in animal models. A relationship between TNF-inhibitors and ischemic colitis has rarely been reported in published literature. We reviewed the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) and published literature for reports of ischemic colitis associated with TNF-α inhibitors in RA patients. Methods: 2,562,390 files between January 2003 and June 2011 from the FDA AERS were downloaded and analyzed using SPSS 20 (IBM Co. Armonk, NY, USA). A search was conducted for reports limited to ‘primary suspect' reactions of ischemic colitis with TNF-α inhibitors, used for treatment of RA. Full length reports were obtained and analyzed to establish authenticity with cases having more likely causes for ischemic colitis such as sepsis eliminated from analysis. The cases were organized by age, gender, specific TNF-α inhibitors, concomitant drugs, and medical comorbidities that are risk factors for ischemic colitis. A PubMed search was performed using MESH terms: “anti-TNF” or “tumor necrosis factor inhibitor” or “TNF-alpha” and “ischemic colitis” separated by the Boolean operator “AND” between the first three and last terms. Results: Thirty-seven primary suspect reports of TNF-α inhibitors associated with ischemic colitis in RA patients were identified. Thirteen (35.1%) cases were reported with infliximab, 12 with adalimumab, eight with etanercept, and four with certolizumab. The majority of the cases were in females (31/37) and those between the ages of 50 and 65 (20/37). Evidence of a colonoscopy, biopsy, or other documented medical confirmation for ischemic colitis was present in 21 cases. One patient had heart disease and five had diabetes. There were no reports describing vasculitis or congestive heart failure. In 20 cases, concomitant medications presented as potential risks for ischemic colitis: 12 patients were on NSAIDs, four on ACE inhibitors, three on estrogen, two each on lisinopril, amlopidine, and beta blockers, and one each on benidipine, olmesartan, and simvastatin. Sixteen patients did not have any listed risk factors or concomitant medications that could increase the risk of ischemic colitis. In the literature, one report of ischemic colitis associated with adalimumab was identified. Conclusion: Our study suggests that TNF-α inhibitors may be initiating factors or co-factors in the development of ischemic colitis in RA patients. Further research to determine the mechanism of this association is warranted.