1539 Drug-Induced Colitis as a Side Effect of Calcitonin Gene-Related Peptide (CGRP) Antagonist for Migraines

Abstract

INTRODUCTION: Drug-induced colitis is a documented though relatively uncommon side effect of several drug classes, and is under-recognized and under-reported. In May 2018, an injectable calcitonin gene-related peptide (CGRP) antagonist, erenumab, was approved by the FDA for migraine prophylaxis. In the following case, this new medication is implicated as a possible cause for severe colitis resembling an inflammatory bowel disease-like picture both clinically and endoscopically. CASE DESCRIPTION/METHODS: A 33-year-old Caucasian female presented with complaints of rectal bleeding, diarrhea, and abdominal pain 2 weeks after starting a CGRP antagonist, erenumab, for chronic refractory migraine headaches. Pertinent laboratory studies showed leukocytosis with bandemia. CT Abdomen/Pelvis showed diffuse colonic wall thickening. Stool studies did not indicate any infectious etiology and an IBD panel was negative. She underwent a colonoscopy that showed severe, deep punched out ulcerations throughout the entire colon. Biopsy showed active colitis. She had a prior colonoscopy in 2009 for work up of IBS, which was endoscopically and microscopically normal. The patient's symptoms and clinical findings resolved after discontinuing the drug. A follow up colonoscopy performed one month after discharge showed evidence of ulcer healing with no new areas of inflammation. DISCUSSION: Blocking CGRP receptors of the central nervous system may reduce headaches, however blocking those of the enteric system can promote breakdown of the colonic mucosal barrier and induce a systemic inflammatory reaction. In animal models, extensive mucosal damage was noted in the subjects receiving CGRP receptor antagonists. This case implies that certain patients may be at risk for developing mucosal barrier disruption from the blockade of the calcitonin gene-related peptide receptor with erenumab or similar drugs. Further research may be needed to elucidate risk factors that may contribute to susceptibility to these deleterious effects. Once those patients that are more at risk are identified, there may be a role for endoscopic surveillance in certain patients taking these medications. While drug-induced colitis is likely to be an uncommon manifestation of blocking CGRP, clinicians should be aware of this potential side effect of targeted therapy and counsel patients receiving this therapy.