People with chronic migraine who overused pain medication had fewer monthly migraine and headache days and fewer days using pain medication when taking the migraine prevention drug atogepant.

“There is a high prevalence of pain medication overuse among people with migraine as they try to manage what are often debilitating symptoms,” said study author Peter J. Goadsby, MD, PhD, of King’s College London and a member of the American Academy of Neurology. “However, medication overuse can lead to more headaches called rebound headaches, so more effective preventive treatments are needed. Our findings are encouraging, suggesting atogepant may help reduce the need for pain medication among people with chronic migraine.”

The study involved 755 participants who had chronic migraine, defined as having 15 or more headache days per month with eight or more qualifying as migraine.

Of this group, 66% met the criteria for medication overuse defined as taking pain medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for 15 or more days in a month, triptans or ergots for 10 or more days a month, or any combination for 10 or more days.

At the start of the study, average monthly migraine days ranged from 18 to 19, and average monthly pain medication days ranged from 15 to 16.

For 12 weeks, participants were either given 30 milligrams (mg) of atogepant twice daily, 60 mg once daily, or a placebo. Atogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in starting the migraine process.

Participants recorded their migraines and headaches in an electronic diary, noting characteristics including duration and intensity, whether they experienced aura or nausea, and if they took other medications.

Researchers found for participants with medication overuse, those taking atogepant twice daily had an average of three fewer migraine days a month and three fewer headache days when compared to those taking placebo. Those taking the drug once a day had two fewer migraine days a month and two fewer headache days compared to placebo. Both groups also had three fewer days of taking pain medications to treat their symptoms when compared to placebo. Researchers say similar reductions were found among participants without medication overuse.

In those with medication overuse, 45% of those taking the drug twice daily and 42% of those taking it once a day had a 50% or more reduction in average monthly migraine days compared to 25% taking the placebo.

The number of people meeting the criteria for medication overuse also declined by 62% among those taking the drug twice daily and by 52% among those taking it once a day.

“Based on our findings, treatment with atogepant may potentially decrease the risk of developing rebound headache by reducing the use of pain medications,” said Goadsby. “This could lead to an improved quality of life for those living with migraine.”

Goadsby noted more studies are needed to evaluate the long-term safety and effectiveness of atogepant, as well as to assess the potential risk of medication overuse relapse among people with migraine.

A limitation of the study was that participants recorded their headaches and medication use in electronic diaries, so it is possible some participants may not have recorded all information accurately.

The study was funded by AbbVie, the maker of atogepant. Goadsby reported that he received personal fees from AbbVie during the study.

The findings of the ELEVATE study were presented on April 25, 2023 at the annual meeting of the American Academy of Neurology.

“These results are exciting, as migraine can be debilitating, and this treatment led to fewer days with migraine for people who had already tried up to four other types of drugs to prevent migraine and either had no improvement or had side effects that outweighed any benefits,” said author Patricia Pozo-Rosich, MD, PhD, Director of Headache and Craniofacial Pain Clinical Unit at Vall d’Hebron University Hospital in Barcelona, Spain.

ELEVATE was a randomized, double-blind, placebo-controlled trial assessing the safety, tolerability, and efficacy of atogepant 60 mg once daily (QD) compared with placebo for the prevention of episodic migraine in adults who previously not responded to two to four classes of oral prophylactic treatments.

The primary endpoint was the change over a period of 12 weeks in mean monthly migraine days (MMDs).

The investigators enrolled 309 subjects. Of these, 56% had already failed to respond to two classes of oral migraine preventive medications, and 44% had already failed to respond to three or more classes.

The researchers reported that subjects in the atogepant 60 mg once daily arm group achieved a mean decrease of 4.20 days in MMDs across the 12-week treatment period, which was statistically significantly greater than the 1.85 day mean reduction achieved by the placebo group (p<0.0001).

Atogepant 60 mg once daily was well tolerated, and safety was consistent with prior studies of the drug.

The authors concluded, “Atogepant demonstrated statistically significant reductions in mean monthly migraine days among participants with CM [chronic migraine] and was safe and generally well-tolerated.

Pozo-Rosich added, “People who thought they may not find a way to prevent and treat their migraines may have hope of finding relief with a tolerable oral easy-to-use drug. This treatment was safe, well-tolerated and effective for people with difficult-to-treat migraine.”