Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study

• Published in: Journal of neurology 2024-05, Vol.271 (5), p.2434-2443
• Main Authors: Barbanti, Piero, Aurilia, Cinzia, Egeo, Gabriella, Proietti, Stefania, D’Onofrio, Florindo, Torelli, Paola, Aguggia, Marco, Bertuzzo, Davide, Finocchi, Cinzia, Trimboli, Michele, Cevoli, Sabina, Fiorentini, Giulia, Orlando, Bianca, Zucco, Maurizio, Di Clemente, Laura, Cetta, Ilaria, Colombo, Bruno, di Poggio, Monica Laura Bandettini, Favoni, Valentina, Grazzi, Licia, Salerno, Antonio, Carnevale, Antonio, Robotti, Micaela, Frediani, Fabio, Altamura, Claudia, Filippi, Massimo, Vernieri, Fabrizio, Bonassi, Stefano
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - immunology; Comorbidity; Dopamine receptors; Female; Headache; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Migraine; Migraine Disorders - drug therapy; Migraine Disorders - immunology; Monoclonal antibodies; Neurology; Neuroradiology; Neurosciences; Original Communication; Pain perception; Prophylaxis; Prospective Studies; Response rates; Time Factors; Treatment Outcome
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-023-12103-4

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