Early and clinically meaningful functional improvement following CGRP monoclonal antibodies in adolescents with migraine: A real-world retrospective study.

Abstract

BackgroundEvidence supporting calcitonin gene-related peptide monoclonal antibody (CGRP mAb) use in adolescents with migraine is limited. Rapid recovery for daily school functioning is particularly important during this stage of life. We aimed to evaluate early functional outcomes in daily and school activities, as well as headache-related outcomes after initiating CGRP mAb therapy in Japanese adolescents with migraine.MethodsThis single-center retrospective cohort study included patients aged 15-17 years who received CGRP mAb therapy (galcanezumab, fremanezumab or erenumab) for migraine between May 2021 and July 2025. The primary outcome was time to clinically meaningful improvement on the Headache Impact Test-6 (HIT-6) scores, comprising a reduction of ≥ 6 points from baseline, and was analyzed using the Kaplan-Meier method. Secondary outcomes included tracking longitudinal HIT-6 trajectories with mixed-effects models for repeated measures, exploratory univariable comparisons for early response (≥ 6-point reduction within 10-14 weeks), questionnaire-based daily functioning assessments, and safety evaluations.ResultsOf 34 adolescents who initiated CGRP mAb therapy, 33 participated in HIT-6 analyses. The cumulative response rate began increasing immediately after treatment initiation, reaching 68.3% (95% confidence interval = 44.6-81.8%) within the 10-14-week period; approximately half of the responders achieved meaningful improvement by weeks 4-6. Mixed-effects models for repeated measures analyses adjusted for baseline HIT-6 scores showed a least-squares mean change of -9.4 points at 12 weeks (95% confidence interval = -14.2 to -4.6; p < 0.001), with benefits sustained over follow-up. Among questionnaire respondents (n = 27), school attendance or concentration in the classroom was the most affected activity before treatment (70.4%) and 88.9% indicated that their primary treatment goals were mostly or partially achieved. Adverse events were reported by 40.7% of participants, primarily injection-site reactions (29.6%), none of which led to therapy discontinuations or modifications.ConclusionsIn this real-world adolescent cohort, CGRP mAb therapy was associated with early and clinically meaningful improvements in headache-related impact and self-reported functioning. Safety and tolerability findings are particularly notable given the limited evidence in this age group. Further prospective controlled studies are warranted to validate these findings and to identify predictors of early functional response.