UM Commentary: A Novel Treatment for Migraines

In a recent article by Lipton et. al. (Lipton RB, Croop R, Stock EG, et al. Rimegepant, an oral calcitonin Gene–Related peptide receptor antagonist, for migraine. N Engl J Med. 2019;381:142-149), the authors attempted to identify a novel pharmaceutical therapy for patients suffering from migraine attacks. The Phase 3 trial reports on the efficacy of the oral calcitonin gene-related peptide receptor (CGRP) antagonist rimegepant for treatment of the acute pain associated with moderate to severe migraines. The authors conclude that rimegepant is effective in the relief of pain for patients suffering from migraine attacks, a common presentation to the ED. However, for several reasons, we are concerned that the conclusions may be overstated.

  • First, there are many effective medications for abortive therapy for migraines currently available such as triptans, traditional anti-emetics and non-steroidal anti-inflammatory medications, and a new class of medication would be especially relevant to patients who are refractory to treatment or who have a contraindication to current treatments. Unfortunately, this study did not identify a subject population resistant to triptans and/or other currently used medications.
  • Second, this study does not inform clinicians if rimegepant is more or less effective than other commonly used medications for migraine attacks because the control arm was a traditional placebo and not standard of care nor an active comparator.
  • Third, the benefit observed in the experimental arm is modest: a 7.6% increase in patients who are pain-free at two hours. This is compared to 12% who are pain-free with no intervention.
  • Fourth, there is inadequate attention paid to a large number of patients in each group (21% and 37%) who requested rescue medication (censured from analysis) and to those patients whose pain relapsed within 48 hours (50% in each group, unchanged.)
  • Finally, the study is susceptible to multiple levels of bias given that every author is either employed by or an owner of the manufacturer Biohaven pharmaceuticals.

For these reasons, we urge caution in the early adoption of this promising new medication. Rimegepant appears to address the unmet need for a novel, alternative therapy for triptan-refractory and contraindicated patients. However, design limitations may misinform the clinical utility of rimegepant in acute migraine treatment.

Ameer KhalekAmeer Khalek '18, MPH is a research fellow for Urgent Matters and a medical student at Touro University Nevada.

Erica ChemtobErica Chemtob is a research fellow for Urgent Matters and a 3rd year Medical Student at the George Washington University School of Medicine & Health Sciences. She received her Bachelor’s Degree in Public Health from the George Washington University and was a Presidential Academic Scholar, a NCAA D1 Student-Athlete on the Varsity Squash Team, and a music minor studying violin. Prior research experience includes the National Institute of Drug Abuse (NIH) and the Washington-Baltimore High Intensity Drug Trafficking Areas Office. She also served as a research assistant for the Center for Advancing Correctional Excellence Lab under Dr. Faye Taxman. She was also a squash coach at Squash On Fire, and performed violin at the Kennedy Center and Carnegie Hall.