Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study
Authors: Barbanti Piero , Egeo Gabriella , Aurilia Cinzia , Torelli Paola , Finocchi Cinzia , d’Onofrio Florindo , d’Onofrio Luigi , Rao Renata , Messina Stefano , Di Clemente Laura , Ranieri Angelo , Autunno Massimo , Sette Giuliano , Colombo Bruno , Carnevale Antonio , Aguggia Marco , Tasillo Miriam , Zoroddu Francesco , Frediani Fabio , Filippi Massimo , Tomino Carlo , Proietti Stefania , Bonassi Stefano ,   for the FRIEND-Study Group, Albanese Maria , Bertolini Marco , Bertuzzo Davide , Bloise Maria , Bono Francesco , Borrello Laura , Camarda Cecilia , Fiorentini Giulia , Grazzi Licia , Le Pera Domenica , Messina Roberta , Querzani Pietro , Salerno Antonio , Strumia Silvia , Valenza Alessandro , Vernieri Fabrizio , Viticchi Giovanna 
Published: March 2023

Abstract
Background
To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures.

Methods
This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21–24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored.

Results
Four hundred ten patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21–24, fremanezumab significantly (p < 0.001) reduced MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM compared to baseline. The proportions of ≥ 50%, ≥ 75% and 100% responders at weeks 21-24were 75.0%, 30.8%, 9.6% (HFEM), and 72.9, 44.8 and 1% (CM). A significant (p < 0.001) decrease in MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM was already present at week 4. The proportions of ≥ 50%, ≥ 75%, and 100% responders at week 4 were 67.6%, 32.4%, 11.8% (HFEM) and 67.3%, 40%, 1.8% (CM). CM remitted to episodic migraine and medication overuse to no-medication overuse in 83.3 and 75% of patients at week 24, and in 80 and 72.4% at week 4. Adverse events were rare (2.4%), mild and transient. No patient discontinued treatment for any reason.

Conclusions
Fremanezumab is characterized by an early and sustained efficacy in HFEM and CM patients with multiple preventive treatment failures in real-life, revealing an optimal safety and tolerability profile.