Effects of Pausing and Re-Initiating Fremanezumab After Continuous 24-Month Treatment for Preventing Difficult-To-Treat Migraine: Prospective, Multicenter, Real-World Data From the GRASP Study Group.

This study, designed by the Greek Research Alliance for Studying headache and Pain (GRASP), aimed to (i) prospectively evaluate the effects of treatment cessation in fremanezumab-responsive patients after 2 years exposure and (ii) assess variations in response rates after migraine worsening and treatment re-initiation. We analyzed 149 patients with high-frequency episodic (HFEM) or chronic migraine (CM), who completed 24 months of fremanezumab, and mandatorily paused fremanezumab and re-initiated it after their migraine worsened. To assess longitudinal variations mostly in monthly migraine/headache days (MMD/MHD) and other efficacy variables, patients were interviewed at baseline (T0), at month 3 (T1), month 24 (T2), treatment pause period (T3), and at month 3 after fremanezumab re-initiation (T4). The primary objective was to assess the ≥ 50% and ≥ 75% response rates at T4, compared to T3 and T2. Migraine relapsed in previous responders at T3, while fremanezumab re-initiation was not equally effective, as evidenced by lower ≥ 50% response rates, mostly in CM. At T4, 6 (9.7%) previously responsive HFEM patients and 27 (31%) previously responsive CM patients failed to obtain ≥ 50% MMD/MHD reduction, compared to T3. The rate of both HFEM and CM super-responders, obtaining a ≥ 75% response at T3, also dropped at T4. Discontinuation of fremanezumab after month 24 leads to rising MMD/MHDs. After fremanezumab re-initiation, a relatively reduced effectiveness in the first 3 months might occur, compared with the pre-fremanezumab cessation. Overall, our findings doubt the rationale behind mandated anti-CGRP treatment pauses in migraine prophylaxis.