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. 2024 Jun;13(3):611-624.
doi: 10.1007/s40120-024-00591-z. Epub 2024 Mar 7.

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study

Piero Barbanti #  1   2 , Gabriella Egeo #  3 , Stefania Proietti  4   5 , Florindo d'Onofrio  6 , Cinzia Aurilia  3 , Cinzia Finocchi  7 , Laura Di Clemente  8 , Maurizio Zucco  8 , Alberto Doretti  9 , Stefano Messina  9 , Massimo Autunno  10 , Angelo Ranieri  11 , Antonio Carnevale  12 , Bruno Colombo  13 , Massimo Filippi  13 , Miriam Tasillo  14 , Steno Rinalduzzi  14 , Pietro Querzani  15 , Giuliano Sette  16 , Lorenzo Forino  6 , Francesco Zoroddu  17 , Micaela Robotti  18 , Alessandro Valenza  19 , Cecilia Camarda  20 , Laura Borrello  21 , Marco Aguggia  22 , Giovanna Viticchi  23 , Carlo Tomino  24 , Giulia Fiorentini  25 , Bianca Orlando  3 , Stefano Bonassi  26   5 , Paola Torelli  27 ; Italian Migraine Registry study group
Affiliations

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study

Piero Barbanti et al. Neurol Ther. 2024 Jun.

Erratum in

Abstract

Introduction: Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities.

Methods: A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates.

Results: Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period.

Primary endpoint: fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason.

Conclusion: This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.

Keywords: CGRP monoclonal antibody; Disability; Fremanezumab; Long-term treatment; Medication overuse; Migraine treatment; Psychiatric comorbidities; Real-world.

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Conflict of interest statement

Piero Barbanti received travel grants, honoraria for advisory boards, speaker panels or clinical investigation studies from Abbvie, Alder, Allergan, Amgen, Angelini, Assosalute, Bayer, Biohaven, ElectroCore, Eli-Lilly, Fondazione Ricerca e Salute, GSK, Lundbeck, Lusofarmaco, 1MED, MSD, New Penta, Noema Pharma, Novartis, Pfizer, Stx-Med, Teva, Visufarma, Zambon and serves as President with Italian Association of Headache Sufferers. Gabriella Egeo received travel grants and honoraria from Eli Lilly, Novartis, New Penta, Lundbeck and Ecupharma. Cinzia Aurilia received travel grants from FB-Health, Lusofarmaco, Almirall, Eli Lilly Novartis and Teva. Florindo d'Onofrio received travel grant, honoraria as a speaker or for partecipating in advisory boards from Novartis, Teva, Neopharmed Gentili, Qbgroupsrl, K link srl and Eli Lilly. Cinzia Finocchi received grants and honoraria from Novartis, Teva, Lilly, Lundbeck, Pfizer. Angelo Ranieri received speaker honoraria from TEVA, Ely Lilly, AIM Group. Antonio Carnevale has no disclosures to declare. Bruno Colombo has received congress fee reimbursements from Teva, Novartis, Pfizer. Massimo Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Alessandro Valenza received grants from Teva, Lilly, Lundbeck, Pfizer. Marco Aguggia received grants from Novartis and Lilly. Paola Torelli received travel grants and honoraria from Allergan, Teva, Eli Lilly and Novartis. Stefania Proietti, Laura Di Clemente, Maurizio Zucco, Alberto Doretti, Stefano Messina, Massimo Autunno, Miriam Tasillo, Steno Rinalduzzi, Pietro Querzani, Giuliano Sette, Lorenzo Forino, Francesco Zoroddu, Micaela Robotti, Cecilia Camarda, Laura Borrello, Giovanna Viticchi, Carlo Tomino, Giulia Fiorentini, Bianca Orlando and Stefano Bonassi have no disclosures to declare.

Figures

Fig. 1
Fig. 1
Patients’ disposition
Fig. 2
Fig. 2
Mean change in monthly migraine days/monthly headache days (MMD/MHD) (a), monthly analgesic medications (b), Numerical Rating Scale (NRS) score (c), Headache Impact Test-6 (HIT-6) score (d), and Migraine Disability Assessment Scale (MIDAS) score (e) from baseline to week 48 in patients affected by high-frequency episodic migraine (HFEM, n = 49) or chronic migraine (CM, n = 81)
Fig. 3
Fig. 3
Proportion of patients with a ≥ 50%, ≥ 75%, or 100% reduction in monthly migraine/headache days at week 12, 24, and 48 compared to baseline (data refer to all patients with migraine)
Fig. 4
Fig. 4
Proportion of patients with a ≥ 50%, ≥ 75%, or 100% reduction in monthly migraine/headache days at week 48 compared to baseline. All, all patients; HFEM, high-frequency episodic migraine; CM, chronic migraine; All + psy (dotted bars), all patients with migraine with psychiatric comorbidities; CM + MO (dotted bars), patients affected by CM with medication overuse; CM + MO + psy (dotted bars), patients affected by CM, medication overuse, and psychiatric comorbidities
Fig. 5
Fig. 5
Proportion of patients remitting from medication overuse (MO) to no medication overuse (no-MO) (red bars), and from chronic migraine (CM) to episodic migraine (EM) (blue bars)
Fig. 6
Fig. 6
Treatment-emergent adverse events (TEAE) occurred in the study population [patients who had been treated for at least 48 weeks (≥ 12 fremanezumab doses), n = 130, white bars] and in the safety population [patients who had received ≥ 1 fremanezumab dose, n = 533, gray bars)]
See this image and copyright information in PMC

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