Oral CGRP receptor antagonists have been approved for migraine prevention without ever being compared directly against the conventional oral drugs they were meant to displace. TEMPLE did that comparison. This phase 3b double-dummy trial across 12 countries randomised 545 adults with at least four migraine days a month to atogepant 60 mg once daily or topiramate at the highest tolerated dose of 50, 75 or 100 mg daily, with a 24-week double-blind period.
The primary endpoint was tolerability, and the gap was large. Discontinuation because of treatment-emergent adverse events was 12% on atogepant (33 of 273) and 30% on topiramate (79 of 267), relative risk 0.4 (95% CI 0.3 to 0.6, p<0.0001). Treatment-related adverse events of any kind were 56% versus 78%. Serious events were rare in both arms — six on atogepant, three on topiramate — with one anaphylactic reaction on atogepant judged drug-related.
Efficacy went the same way. At least a 50% reduction in monthly migraine days was achieved by 64% on atogepant and 39% on topiramate, relative risk 1.6 (95% CI 1.4 to 2.0). Mean monthly migraine days fell by 6.3 versus 4.5, a treatment difference of 1.8 days (95% CI -2.5 to -1.0).
The qualifier that matters most in Indian practice is cost, which the trial does not address. Atogepant is many times the price of topiramate, and for a patient paying directly the calculation is different from the one this trial implies. The useful reframing is that topiramate's problem is measurable — three in ten stop it — so the sequencing question becomes whether to try the cheap drug first and accept a high failure rate, or to move earlier for patients in whom another topiramate failure would mean months lost.
- Expect roughly three in ten patients to stop topiramate for adverse effects within six months, and counsel accordingly
- Where cost allows, atogepant is both better tolerated and more effective as an oral preventive
- Do not read this as a reason to abandon topiramate where it is affordable and tolerated — it still halved migraine days in 39% of patients
- Move on quickly from a topiramate trial that is causing cognitive slowing, paraesthesia or weight loss rather than pushing the dose
- Note the trial population was 96% White and 89% female, so tolerability estimates may not transfer exactly
The statistics, in plain English
The primary endpoint here was tolerability, not efficacy, which is unusual and deliberate: the trial was designed around the observation that topiramate's real-world failure is people stopping it. A relative risk of 0.4 for discontinuation means atogepant patients were about 60% less likely to stop, and the interval 0.3 to 0.6 is tight. The efficacy difference of 1.8 monthly migraine days is modest in absolute terms but sits alongside a much larger difference in the responder rate, which is the number patients actually experience. One caution: the trial was funded by the manufacturer of atogepant and used a fixed atogepant dose against a titrated topiramate dose, which is the design most favourable to the sponsor's drug on tolerability.
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