Ischaemic Colitis in Rheumatoid Arthritis Patients Receiving Tumour Necrosis Factor-α Inhibitors: An Analysis of Reports to the US FDA Adverse Event Reporting System

Background Tumour necrosis factor-alpha (TNF-alpha) inhibitors are immunosuppressants, approved for the treatment and maintenance of rheumatoid arthritis (RA). Immunosuppression has been shown to induce ischaemic colitis (IC) in an animal model; however, a relationship between TNF inhibitors and IC has rarely been reported in the published literature. Objective The aim of this study was to better characterize the association between TNF-alpha inhibitors with IC in RA patients, by analysing adverse event reports submitted to the US FDA Adverse Event Reporting System (AERS) and the published literature. Methods The FDA AERS database was searched and we identified all reports between January 2003 and June 2011. The search was limited to an indication of RA, a 'primary suspect' drug of TNF-alpha inhibitors and a reaction of IC. Full-length reports were obtained and analysed utilizing the Freedom of Information Act. The cases were organized by age, sex, type of TNF-alpha inhibitor, concomitant drugs and medical co-morbidities. Cases were labelled as definite, probable, possible or doubtful drug-induced adverse events based on the Naranjo Scale. A PubMed search was performed to obtain published literature documenting events of anti-TNF-associated IC. Results Twelve cases were eliminated because of more likely causes for IC. Thirty-five primary suspect reports of TNF-alpha inhibitors associated with IC in RA patients were identified in the FDA AERS. Thirteen cases were reported with infliximab, 12 with adalimumab, 7 with etanercept and 3 with certolizumab. The majority of the cases were in females (29/35) and those between the ages of 50 and 65 years (18/35). Use of the Naranjo Scale revealed 17 probable and 18 possible cases of anti-TNF-induced IC. In the literature, one report of IC associated with adalimumab was identified. Conclusion TNF-alpha inhibitors may be initiating factors or co-factors in the development of IC in RA patients, and further research to determine the mechanism of this association is warranted.