BACKGROUND: Fremanezumab, a humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, is approved for the prevention of migraine in adults. Evidence from randomized, controlled trials in children and adolescents is needed.
METHODS: We randomly assigned participants 6 to 17 years of age with a diagnosis of episodic migraine (defined as migraine for =6 months and a history of =14 headache days per month) to receive monthly subcutaneous injections of fremanezumab (120 mg for participants with a body weight of <45 kg and 225 mg for those with a body weight of =45 kg) or matched placebo for 3 months. Participants were allowed to use migraine-specific medications to treat acute headaches. The primary end point was the change from baseline in the average number of migraine days per month. Key secondary end points included the change in the number of days per month with headache of at least moderate severity and a reduction of 50% or more in the number of migraine days per month.
RESULTS: Of 237 participants who underwent randomization, 234 were included in the full analysis population: 123 in the fremanezumab group (36 received the 120-mg dose and 87 received the 225-mg dose) and 111 in the placebo group. Fremanezumab reduced the number of migraine days per month by 2.5 as compared with 1.4 with placebo (difference, 1.1; P = 0.02) and the number of days per month with headache of at least moderate severity by 2.6 as compared with 1.5 with placebo (difference, 1.1; P = 0.02). The percentage of participants who had a reduction of 50% or more in the number of migraine days per month was 47.2% with fremanezumab and 27.0% with placebo (P = 0.002). Injection-site erythema was the most common adverse event with fremanezumab (9.8% of participants, vs. 5.4% with placebo).
CONCLUSIONS: Among children and adolescents with episodic migraine, fremanezumab resulted in greater reductions in the number of migraine days and headache days than placebo. Injection-site erythema was the most common adverse event with fremanezumab. Longer follow-up is required to further understand the efficacy and safety of the drug in this population. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT04458857.).
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
NOTE: Pharma-sponsored and a high placebo response.
Physician rater
Looks like a marginal clinical benefit.
Physician rater
Certainly, episodic migraine that is difficult to treat does occur occasionally in children and adolescents. To date, there has been no reliable evidence regarding the use of fremanezumab in this age group. However, when I see that the use of this very expensive substance (in Germany > €1,300 every 3 months) leads to one less migraine day per month, I don't think we really need to take note of this study. In addition, the baseline characteristics do not mention what treatments the patients received up to that point. There is no comparison with other prophylactic drugs.
Physician rater
The benefit of fremanezumab in children and adolescents needs to be confirmed with long-term follow-up data. External validity is good due to the wide geographic variability of randomized patients and the safety is good. A cost-effectiveness study needs to be done.
Physician rater
The article provides high-quality evidence on the use of monoclonal antibodies in children and adolescents with migraine.
, McMaster University