by Isabella Colonna
For our paper of the month for February, we have selected Hershey AD, Szperka CL, Barbanti P, Pozo-Rosich P, Bittigau P, Barash S, Bryson J, Kessler Y, Carmeli Schwartz Y, Ramirez Campos V, Ning X. Fremanezumab in Children and Adolescents with Episodic Migraine. N Engl J Med. 2026 Jan 15;394(3):243-252. doi: 10.1056/NEJMoa2504546. PMID: 41534042.
Migraine is a common neurological disorder in childhood and adolescence, with an estimated overall prevalence of 11%. Fremanezumab is a humanised monoclonal antibody that selectively targets calcitonin gene–related peptide (CGRP) and has been shown to reduce headache frequency. It has been approved in several countries as a preventive treatment for episodic and chronic migraine in adults.
This Paper of the Month reports the results of a phase 3, randomised, multicentre, placebo-controlled trial designed to evaluate the efficacy and safety of fremanezumab in children and adolescents aged 6–17 years with episodic migraine. The study included a 28-day baseline period, during which participants maintained a headache diary, followed by a three-month double-blind treatment period.
After randomisation, 123 participants received fremanezumab at a dose of either 120mg (n = 36) or 225mg (n = 87), according to body weight, while 111 participants were assigned to the placebo group. Compared with placebo, treatment with fremanezumab resulted in a statistically significant reduction in the mean number of migraine days per month as well as in the number of days per month with headache of at least moderate severity. In addition, the proportion of patients achieving a ≥50% reduction in monthly migraine days was significantly higher in the fremanezumab group than in the placebo group (47.2% vs 27%). Moreover, patients treated with fremanezumab used acute headache medication approximately two fewer days per month, compared with about one fewer day per month among those receiving placebo (p=0.002).
With regard to safety, at least one adverse event was reported in 55.3% of participants in the fremanezumab group and in 49.1% of those in the placebo group. Most adverse events were non-serious and mild to moderate in severity; the most frequently reported adverse events among patients receiving fremanezumab were injection-site reactions.
In summary, in this phase 3 trial, three months of treatment with fremanezumab in children and adolescents with episodic migraine was associated with significant reductions in the number of migraine days; days with headache of at least moderate severity; and days of acute headache medication use, without the emergence of safety concerns. Longer-term follow-up studies are warranted to further assess the sustained efficacy and long-term safety of fremanezumab in this population.
