Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study
Year: 2024
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). METHODS: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. RESULTS: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain-either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)-a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). CONCLUSION: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2-3 months of treatment.
Source: Journal of Neurology
Authors: Piero Barbanti, Cinzia Aurilia, Gabriella Egeo, Stefania Proietti, Florindo D’Onofrio, Paola Torelli, Marco Aguggia, Davide Bertuzzo, Cinzia Finocchi, Michele Trimboli, Sabina Cevoli, Giulia Fiorentini, Bianca Orlando, Maurizio Zucco, Laura Di Clemente, Ilaria Cetta, Bruno Colombo, Monica Laura Bandettini di Poggio, Valentina Favoni, Licia Grazzi, Antonio Salerno, Antonio Carnevale, Micaela Robotti, Fabio Frediani, Claudia Altamura, Massimo Filippi, Fabrizio Vernieri, Stefano Bonassi, ERT; for the Italian Migraine Registry study group
Institutions: San Raffaele University of Rome, IRCCS San Raffaele Roma, Azienda Ospedaliera S.Giuseppe Moscati, University of Parma, Ospedale San Paolo, Azienda Sanitaria Locale N. 2 Savonese, Magna Graecia University, Istituto delle Scienze Neurologiche di Bologna, Azienda Ospedaliera San Camillo-Forlanini, Vita-Salute San Raffaele University, Ospedale Policlinico San Martino, Fondazione IRCCS Istituto Neurologico Carlo Besta, Azienda Ospedaliera San Giovanni Addolorata, Ospedale San Filippo Neri, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Campus Bio Medico University Hospital
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,590
OpenAlex ID: W4390944115