PRODROME trial shows CGRP in migraine prodrome can stop headache and reduce severity
11 December, 2023: Research shows that taking a specific class of migraine medication during the prodromal phase reduces the development and severity of the subsequent headache. In the randomised, placebo-controlled 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.
The findings were presented at 17th European Headache Congress (EHC) and were also recently published online in The Lancet.
[Read clinical article: Monoclonal CGRP- (R) antibodies for the prevention of migraine by Uwe Reuter in ACNR]
The prodrome, the earliest stage of a migraine attack, 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.
At present there isn’t much which can be done to prevent the headache. Triptans are only recommended during the headache phase, due to the risk of medication overuse headache and the fact they don’t work during the prodromal phase. However, ubrogepant and other members of the “gepant” class do not seem to have the tendency for medication overuse problems. Instead, they seem to have a preventative effect and also reduce severity. The incidence of moderate to severe headache was almost halved when ubrogepant was taken in the prodrome.
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.
Peter Goadsby, Study Investigator
Goadsby 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.
He said the current study opens up a whole new area of interest, emphasising the clinical value of identifying the prodrome in individuals with migraine, better characterising the symptomology of the prodrome and understanding more about how to treat it.
The trial
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 PRODROME study was funded by AbbVie.
[Read more Headache articles in ACNR]
