Atogepant was better tolerated and more effective than topiramate for migraine prevention

Design

Phase 3b, randomised, double-blind, double-dummy, active-controlled trial

Population

545 adults with at least 4 migraine days per month

Primary outcome

Discontinuation due to adverse events over 24 weeks

Effect

12% vs 30%; RR 0.4 (95% CI 0.3–0.6); ≥50% responders 64% vs 39%

TEMPLE was a phase 3b double-dummy trial in 12 countries comparing atogepant 60 mg daily with topiramate at the highest tolerated dose (50–100 mg daily) in 545 adults with at least four migraine days a month. It was published in July.

Over 24 weeks, 12% stopped atogepant because of adverse events against 30% stopping topiramate (RR 0.4, 95% CI 0.3–0.6). Treatment-related adverse events occurred in 56% vs 78%. Migraine days halved in 64% on atogepant and 39% on topiramate (RR 1.6, 1.4–2.0), with a mean reduction of 6.3 vs 4.5 days a month. One anaphylactic reaction on atogepant was judged drug-related.

This is the first head-to-head evidence that an oral gepant beats a standard first-line preventive on both tolerability and efficacy. The trial was industry-funded, and cost is the main barrier: topiramate is cheap everywhere, and atogepant availability and price in India should be checked locally.

• Consider atogepant for patients who cannot tolerate topiramate or in whom it has failed.
• Warn patients starting topiramate that almost a third stopped it for side effects in this trial.
• Expect about 64% of atogepant users to halve their migraine days, against 39% on topiramate.
• Weigh cost and access — topiramate remains a reasonable first choice where atogepant is unaffordable.
• Review preventive efficacy at 3 months using a headache diary.

Why it matters

It challenges the default of starting every migraine prevention with an older, poorly tolerated drug.

Don't overread it

The trial was industry-funded and 96% of participants were White; cost-effectiveness was not assessed.

The statistics, in plain English

A relative risk of 0.4 for discontinuation means patients were 60% less likely to stop atogepant because of side effects. A relative risk of 1.6 for response means 60% more people halved their migraine days. Both intervals are well clear of 1.0.

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