Rimegepant Linked to Increased Rectal Compliance, Reduced Rectal Sensation in IBS, With Ayah Matar, MD

New research on rimegepant for the treatment of irritable bowel syndrome (IBS) highlights reduced rectal sensation and increased rectal compliance in participants with non-constipation IBS and abdominal pain.1

Ayah Matar, MD, a postdoctoral researcher at Mayo Clinic, presented the late-breaking abstract at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting, evaluating the safety and efficacy of rimegepant by measuring abdominal pain, bowel movements, rectal compliance and sensation, and gastrointestinal/ colonic transit.

Calcitonin gene-related peptide (CGRP) is a neurotransmitter expressed by visceral afferents and digestive organs. Rimegepant, a CGRP receptor antagonist, is the only oral CGRP antagonist approved in the United States for the acute and preventive treatment of migraine. Preclinical studies have shown CGRP significantly reduces visceral hypersensitivity to colonic distension in rats.2

In this randomized, double-blind, placebo-controlled study, investigators sought to assess whether rimegepant, at the same dosage used for migraine prevention, could alleviate IBS-related abdominal pain and bowel symptoms.

“There are multiple medication options [for IBS], but they have known side effects, and some of those medications can be only given to a specific population, such as women under 35,” said Matar in an interview with HCPLive. “This leaves the remaining patients with unmet pharmacological needs and treatment.”

Participants received either a placebo (n = 12) or oral rimegepant 75 mg every other day (n = 12). Eligible participants had non-constipated IBS with abdominal pain meeting Rome III criteria. The study included a 2-week run-in, a 4-week treatment phase, and a 4-week post-treatment follow-up.

Abdominal pain and bowel movements were recorded in daily diaries throughout the study. Rectal compliance and sensory thresholds were assessed using a validated barostat method with stepwise distensions of 0–44 mmHg in 4 mmHg increments. During phasic rectal distensions at 12, 24, and 36 mmHg, investigators used a 100 mm visual analog scale to record sensations of gas, urgency, and pain.

According to data presented at ACG, no significant differences were observed between groups regarding abdominal pain or bowel movements at baseline or during treatment. Investigators saw an association between rimegepant treatment and reductions in sensations of gas, urgency, and pain during 24 mmHg rectal distensions (P < .05), as well as gas and urgency sensations during 36 mmHg rectal distensions (P < .05).

Compared with placebo, rimegepant was associated with modest differences in daily symptom scores and rectal compliance. Median change from baseline in abdominal pain was -22.6 (Interquartile Range [IQR], -30.3 to -8.1) with placebo and -12 (IQR, -16.9 to -6.4) with rimegepant (P = .41).

For bowel movement frequency, investigators observed a median change of –0.2 (IQR, -0.8 to 0) with rimegepant (P = .043) compared to -0.9 (IQR, -1 to -0.4) with placebo, indicating a statistically significant difference. No significant differences were observed for bowel movement consistency (P = .61), bowel movement urgency (P = .81), or bloating (P = .51).

Investigators noted a statistically significant difference in rectal compliance between groups, with a median change of 2.1 (IQR, -1.3 to 7) for rimegepant (P = .041) and -0.1 (IQR, -4.2 to 2.2) for placebo.

“When I say it reduced rectal compliance, I mean that patients had a stiffer rectum, yet we also saw a reduced sensation to pain. This tells us that rimegepant was acting on the visceral effects and not just reducing pain sensation because of a looser rectum,” said Matar. “It's not just about reducing the sensation of the rectum, it's also about increasing the threshold of pain, so there was a need for more pressure to get a response or pain in the participants who received rimegepant.”

Editor’s Note: Matar reports no relevant disclosures.

References:

1. Matar, A, Halawi, H, Wang, I, et al. A Placebo-Controlled Trial of CGRP Antagonist Rimegepant on Visceral Sensation and Symptoms in Participants With Non-Constipated IBS Pain (Late-Breaking Abstract). Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

2. Scott LJ. Rimegepant: First Approval. Drugs. 2020;80(7):741-746. doi:https://doi.org/10.1007/s40265-020-01301-3