Date: January 10th, 2020

Reference: Dodick DW et al. Ubrogepant for the Treatment of Migraine. NEJM 2019

Guest Skeptic: Dr. Anand Swaminathan is an Assistant Professor of Emergency Medicine at St. Joseph’s Hospital in Paterson, NJ. He is also the managing editor of EM:RAP and associate editor at REBEL EM.

Case: A 23-year-old man with a history of migraines presents with two days of headache, nausea and photo-photophobia typical of his prior migraines. He’s tried a number of medications at home including ibuprofen, acetaminophen, aspirin and sumatriptan without any considerable improvement in symptoms. You start to offer him your standard medications like metoclopramide and haloperidol when he asks about a new drug he heard about called ubrogepant.

Background: Migraine headaches are a chronic neurologic disease characterized by throbbing, often unilateral headaches that are often associated with nausea, vomiting, photophobia and phonophobia. It is a common disease and can be severe enough to impede on people’s lives.

Headaches themselves are not only a common emergency department presentation but one that is filled with potential dangers. There are a number of causes of headache that are life and limb threatening – subarachnoid hemorrhage (SGEM#201), meningitis, encephalitis, cerebral venous thrombosis, vertebral artery dissection among other things but, most headaches are benign in nature.

There is an international classification system of headaches (IHS 2018). The current system classifies them into primary and secondary headaches. An important part of our job as emergency physicians is to differentiate the lethal headache from the benign headache.

Though we rarely make a de novo diagnose of migraines in the emergency department, many patients with migraines present to us for symptom management. The pathophysiology of migraines is both complicated and poorly understood but there are a number of potential treatments including NSAIDs, acetaminophen, aspirin, neuroleptics, triptans and even propofol.

More recently, calcitonin gene-related peptide antagonists (CGRPs) have emerged as a new potential treatment. The first big study that came out on these drugs was published in the NEJM in 2019 and was entitled Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist for Migraine (Lipton et al).

Now, we have a second study published in the NEJM on a related drug, ubrogepant.

Clinical Question: Does ubrogepant increase the percentage of patients who were free from pain and absent of the most bothersome migraine-associated symptom at two hours from initial dose in comparison to placebo?

Reference: Dodick DW et al. Ubrogepant for the Treatment of Migraine. NEJM 2019

* Population: Adult patients (18-75 years of age) with at least a one-year history of migraine with or without aura that met criteria from the International classification of headache disorders and had migraine onset before the age of 50. Patients had to have a history of migraines between 4-72 hours and a history of migraine attacks separated by at least 48 hours of freedom from headache. Additionally, they had to have suffered from two to eight migraines per month over the last three months.

* Exclusions: Patients with 15 or more headaches/month on average in the previous six months. Hard to distinguish the type of headache.