Achieving International Headache Society-aspired optimal migraine control in fremanezumab-treated patients: A post-hoc analysis of a real-world, prospective study from the GRASP study group.

ObjectiveTo evaluate whether the conventional ≥50% reduction in monthly migraine days (MMDs) accurately reflects clinically meaningful benefit compared with IHS-aspired migraine control definitions in difficult-to-treat high-frequency episodic migraine (HFEM).MethodsIn this post-hoc analysis of a prospective, real-world registry, conducted by the Greek Research Alliance for the Study of Headache and Pain (GRASP), 114 HFEM patients who had failed ≥3 preventive therapies and achieved a sustained ≥50% reduction in MMDs with monthly fremanezumab over 24 months, were included. Treatment response (≥50% and ≥75% MMD reduction) and IHS-defined control states (freedom, optimal, modest, insufficient control) were assessed using headache diaries at baseline (T0), month 12 (T1), and month 24 (T2). Secondary outcomes included headache intensity, analgesic use, and migraine-related disability.ResultsAt T1, fremanezumab significantly improved all efficacy and disability outcomes (p < 0.001), with mean MMDs reduced from 11.9 at baseline to 5.1 at T1. While 78.1% achieved ≥50% MMD reduction, only 19.3% reached optimal control (<4 MMDs), highlighting a mismatch between relative response and true disease control. At T2, MMDs further declined to 4.3, while optimal control increased to 29.8% and insufficient control declined to 7.8%. Overall, most patients remained moderately controlled (60.6%) with residual 4-6 MMDs. Non-prior exposure to other anti-CGRP therapies emerged as the only independent predictor of optimal long-term control (OR:2.1; p = 0.03).ConclusionAchieving a ≥ 50% MMD reduction with CGRP-targeted therapies may not always correspond to clinically-meaningful benefit. More ambitious outcome measures are essential for more accurately evaluating treatment effectiveness and achieving clinically-meaningful reduction of migraine's disability.