EAN 2026 | Clinical trial and real-world evidence for anti-CGRP antibodies and gepants in migraine

It’s the first time in the headache field that we have such a large number of trials with a drug for the prevention of migraine. And if we consider all the randomized control studies, Phase IIb and Phase III, of molecules used to prevent migraine, but also for the acute treatment, and I mean CGRP targeting treatments, we have 25 trials, and 24,000 patients included. So really a very large amount of patients considered. These trials involved four monoclonal antibodies, erenumab, galcanezumab, fremanezumab, and eptinezumab, and also two gepants, atogepant and rimegepant. And these trials included and considered a large series of patients and also different clinical scenarios. Patients affected by episodic migraine, by chronic migraine, and also those patients affected by episodic or chronic migraine with prior treatment failures from two to four. Fremanezumab was also studied in randomized control studies in children, so in the pediatric population, and also in patients affected by comorbid major depressive disorder. The main results, half of the patients reached after three months on average, at least 50% reduction in monthly migraine days compared to baseline. And one third of these patients, after only three months, reached a 75% reduction in monthly migraine days compared to baseline. The proportion is likely less for patients who have failed from two to four prior preventive treatments. But this is the efficacy. What about the tolerability and safety? Very good results indeed. And I would say very good results indeed, mostly for monoclonal antibodies, but for all these trials, so monoclonal antibodies and gepants, the proportion of adverse events was similar in patients treated with the active drug and in those treated with placebo. What randomized control studies demonstrated is a slightly higher proportion of gastrointestinal symptoms, including nausea, constipation, or anorexia, or weight loss, in patients treated with gepants, but with a very, very low discontinuation rate. What did the real-world evidence study add? For the first time, we noticed that actually these drugs work in real life even better than that expected from randomized controlled studies. And indeed, these studies were mainly carried out in Italy, where we have a registry, and so these trials have been prospective multicenter studies. And we documented that up to 75% of patients responded within three or six months, with an even lower proportion of patients with adverse events. We also documented that in real life there may happen a late or ultra-late response to monoclonal antibodies and this points to the need to keep treating patients, not stopping after a short period of time.

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