BARCELONA, SPAIN — In the randomized, placebo-controlled crossover PRODROME trial, treatment with ubrogepant (Ubrelvy) 100 mg, one of the new CGRP receptor antagonists, during the prodrome prevented the development of moderate/severe headache at both 24 hours and 48 hours post-dose. The medication also reduced headache of any intensity within 24 hours and functional disability compared with placebo.
“This represents a totally different way of treating a migraine attack – to treat it before the headache starts. This is a paradigm shift in the way we approach the acute treatment of migraine,” study investigator Peter Goadsby, MBBS, MD, PhD, professor of neurology at Kings College London, UK, said in an interview.
The findings were presented at 17th European Headache Congress (EHC) and were also recently published online in The Lancet.
A New Way to Manage Migraine?
The prodrome is usually the earliest phase of a migraine attack and is believed to be experienced by the vast majority of patients with migraine. It consists of various symptoms, including sensitivity to light, fatigue, mood changes, cognitive dysfunction, craving certain foods, and neck pain, which can occur several hours or days before onset.
Dr. Goadsby notes that, at present, there isn’t very much a patient can do about the prodrome.
“We advise patients if they feel an attack is coming not to do anything that might make it worse and make sure they have their acute treatment available for when the headache phase starts. So, we just advise people to prepare for the attack rather than doing anything specific to stop it. But with new data from this study, we now have something that can be done. Patients have an option,” he said.
Dr. Goadsby explained that currently patients are not encouraged to use acute migraine medications such as triptans in the prodrome phase.
“There is actually no evidence that taking a triptan during the prodromal phase works. The advice is to take a triptan as soon as the headache starts, but not before the headache starts.”
He noted that there is also the problem of medication overuse that is seen with triptans, and most other medications used to treat acute migraine, which leads to medication overuse headache, “so we don’t like to encourage patients to increase the frequency of taking triptans for this reason.”
But ubrogepant and other members of the “gepant” class do not seem to have the propensity for medication overuse problems. “Rather, the more a patient takes the less likely they are to get a headache as these drugs also have a preventative effect,” Dr. Goadsby said.
Major Reduction in Severity
The PRODROME trial was conducted at 75 sites in the United States in 518 patients who had at least a 1-year history of migraine with or without aura and a history of two to eight migraine attacks per month with moderate to severe headache in each of the 3 months before study entry.
Participants underwent a rigorous screening period during which they were required to show that they could identify prodromal symptoms that were reliably followed by migraine headache within 1-6 hours.
They were randomly assigned to receive either placebo to treat the first qualifying prodrome event and ubrogepant 100 mg to treat the second qualifying prodrome event or vice versa, with instructions to take the study drug at the onset of the prodrome event.
Efficacy assessments during the double-blind treatment period were recorded by the participant in an electronic diary. On identifying a qualifying prodrome, the patient recorded prodromal symptoms, and was then required to report the absence or presence of a headache at regular intervals up to 48 hours after the study drug dose. If a headache was reported, participants rated the intensity as mild, moderate, or severe and reported whether rescue medication was taken to treat it.
The primary endpoint was absence of moderate or severe intensity headache within 24 hours after study-drug dose. This occurred after 46% of 418 qualifying prodrome events that had been treated with ubrogepant and after 29% of 423 qualifying prodrome events that had been treated with placebo (odds ratio, 2.09; 95% CI, 1.63 - 2.69; P < .0001).
“The incidence of moderate to severe headache was almost halved when ubrogepant was taken in the prodrome,” Dr. Goadsby reported.
Ubrogepant also showed similar impressive results for the secondary endpoints in the absence of moderate to severe headache within 48 hours post-dose and the absence of any headache of any intensity at 24 hours.
Little to No Disability
The researchers also evaluated functional ability, and more participants reported “no disability or able to function normally” during the 24 hours after treatment with ubrogepant than after placebo (OR, 1.66; P < .0001).
Other findings showed that the prodromal symptoms themselves, such as light sensitivity and cognitive dysfunction, were also reduced with ubrogepant.
Dr. Goadsby said he was pleased but not surprised by the results, as the “gepant” class of drugs are used in both the acute treatment of migraine and as preventive agents, although different agents have been approved for different indications in this regard.
“The ‘gepants’ are a class of medication that can be used in almost any way in migraine — to treat an acute migraine headache, to prevent migraine if taken chronically, and now we see that they can also stop a migraine from developing if taken during the initial prodromal phase. That’s unique for a migraine medication,” he said.
While the current study was conducted with ubrogepant, Dr. Goadsby suspects that any of the “gepants” would probably have a similar effect.
He noted that the prodromal phase of migraine has only just started to be explored, with functional imaging studies showing that structural brain changes occur during this phase.
Dr. Goadsby said the current study opens up a whole new area of interest, emphasizing the clinical value of identifying the prodrome in individuals with migraine, better characterizing the symptomology of the prodrome and understanding more about how to treat it.
“It’s the ultimate way of treating migraine early, and by taking this type of medication in the prodromal phase, patients may be able to stop having pain. That’s quite an implication,” he concluded.
The PRODROME study was funded by AbbVie. Dr. Goadsby reports personal fees from AbbVie.
A version of this article appeared on Medscape.com.