Predictive factors of response to anti-CGRP pathway drugs in people with multiple sclerosis

Background: Migraine is common in people with multiple sclerosis (PwMS) and substantially contributes to disability and impaired quality of life. Although (CGRP)-targeting therapies have reshaped migraine prevention, evidence on their use in PwMS remains scarce, particularly in people receiving concomitant disease-modifying therapies (DMTs). Methods: We retrospectively collected data from 17 Italian multiple sclerosis (MS) centers on adult PwMS with comorbid migraine treated with anti-CGRP monoclonal antibodies or gepants in addition to stable DMTs. Monthly headache days (MHDs) and total number of analgesics per month were compared between treatment initiation and last follow-up. MS activity was assessed through clinical relapses, Expanded Disability Status Scale (EDSS), and MRI findings. A ≥ 50% reduction in MHDs defined treatment response. Multivariate regression models were used to explore predictors of response to anti-CGRP therapies. Results: Fifty-four patients were included (46 women; mean age 42.3 years; 85% relapsing MS). Baseline MHDs averaged 19.87 ± 6.97 and declined to 11.40 ± 9.35 at follow-up (p < 0.001), with a parallel decrease in analgesic use (p < 0.001). Responder rate at the last follow-up was 53.7%. MS disease activity remained stable, with no significant changes in relapse rate, EDSS score, or MRI activity. Higher baseline headache burden was associated with greater reduction in MHDs (β=+0.685, p < 0.001), whereas longer MS duration predicted poorer response (OR1.43, 95%CI 1.06-1.92, p = 0.016). Mild adverse events occurred in four patients (7%), without treatment discontinuation. Conclusion: Anti-CGRP pathway therapies provided meaningful migraine improvement in PwMS while maintaining MS stability. MS disease duration and baseline headache frequency may influence therapeutic response to anti-CGRP drugs in PwMS. Clinical trial number: Not applicable.