Is atogepant (Qulipta) effective in reducing headache frequency in adults with chronic migraines?
Atogepant is more effective than placebo in preventing acute migraines in highly selected adults with chronic migraine. While it is unclear if atogepant is any better than other preventive therapies, it is certainly more expensive.
Randomized controlled trial (double-blinded)
The calcitonin gene-related peptide (CGRP) receptor antagonists (the so-called “gepants”) have been used primarily for treating acute (not chronic) migraines. In this industry-sponsored international multicenter study, the researchers enrolled adults with at least 1 year of chronic migraines (at least 15 headache days/month, at least 8 of which are migraines) and who were highly adherent to completing an electronic headache diary during a 4-week baseline screening period. The 142 participating centers identified 1489 potentially eligible participants, of whom 711 were excluded (658 due to “screen failure”) leaving 778 total participants. That translates to only 5 to 6 active participants from each center. After the screening period, the participants were randomized to receive atogepant 30 mg twice daily (n = 257), atogepant 60 mg once daily (n = 262), or placebo (n = 259) for 12 weeks. To preserve the masking, each participant took 2 tablets twice daily. The researchers assessed each participant every 2 to 4 weeks until 16 weeks after randomization. The participants could continue pre-study preventive therapy if the dose was stable for at least 12 weeks before beginning the study. In the event of an acute migraine, the participants could use anything other than a gepant. The researchers used a modified intention-to-treat analysis that included only participants who received at least one dose of study medication and also had at least one evaluable 4-week block of headache diary data in addition to the baseline diary data.
At baseline, the participants averaged approximately 19 migraine days per month. At the end of the study, the average number of migraine days decreased for each group (-7.5 days, -6.9 days, and -5.1 days, respectively). Compared with placebo, participants who took 30 mg atogepant twice daily had 2.4 fewer migraine days and those taking 60 mg atogepant had 1.8 fewer migraine days. Additionally, compared with placebo the participants who took atogepant needed fewer days of acute therapy (-2.6 and -2.1 days, respectively). More atogepant-treated participants experienced at least a 50% reduction in migraine days (43% and 41%, respectively) than those who took the placebo (26%). One would need to treat 6 to 7 adults for 16 weeks with atogepant to decrease migraine frequency by 50%. Adverse effects were slightly more frequent in the atogepant-treated participants (56% and 63%, respectively) than in the placebo group (49%), and those adverse effects were largely gastrointestinal. However, drug discontinuations due to side effects were similar in each group (3% - 5%). Finally, this stuff is expensive. At GoodRx.com, 30 of the 60-mg tablets cost more than $1000 and 60 of the 30-mg tablets are double that. Before recommending this drug to a patient, I’d suggest a trial of other therapies (such as beta-blockers, angiotensin receptor blockers, amitriptyline, or anticonvulsants, or even riboflavin.
Henry C. Barry, MD, MS
Michigan State University
East Lansing, MI