Real world effectiveness of anti-CGRP monoclonal antibodies over three consecutive one-year treatment cycles: An intention-to-treat analysis

• Published in: Cephalalgia Vol. 45; no. 8; p. 3331024251353421
• Main Authors: Vaghi, Gloria, Corrado, Michele, Pocora, Maria Magdalena, Bighiani, Federico, Cammarota, Francescantonio, Antoniazzi, Alessandro, Costantino, Luca, Martinelli, Daniele, Allena, Marta, Ghiotto, Natascia, Guaschino, Elena, Bottiroli, Sara, Iannone, Luigi Francesco, De Cesaris, Francesco, Montisano, Danilo Antonio, Grazzi, Licia, Sances, Grazia, Montomoli, Cristina, Tassorelli, Cristina, De Icco, Roberto
• Format: Journal Article
• Language: English
• Published: England 01.08.2025
• Subjects: Adult; Antibodies, Monoclonal - therapeutic use; Calcitonin Gene-Related Peptide - antagonists & inhibitors; Calcitonin Gene-Related Peptide - immunology; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Migraine Disorders - drug therapy; Prospective Studies; Treatment Outcome; pain; erenumab; fremanezumab; CGRP; galcanezumab; monoclonal antibodies
• ISSN: 0333-1024; 1468-2982; 1468-2982
• DOI: 10.1177/03331024251353421

BackgroundThe present prospective, real-world study aims to assess anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) effectiveness across three consecutive one-year treatment cycles by means of a conservative intention-to-treat (ITT) analysis.MethodsWe enrolled 179 subjects (75.4% females, 51.3 years 95% confidence interval [49.2-53.4] years), 87.2% with chronic migraine and medication overuse) who started mAbs between 2018 and 2020. We recorded clinical data supported by a prospectively filled headache diary up to three one-year treatment cycles. The ITT analysis was performed with a multivariate linear mixed model considering the entire population.ResultsWe observed a marked and consistent reduction in monthly migraine days (MMDs) across the three one-year cycles of treatment: -12.7 )[-11.4 - -14.1] at end of the first year of treatment (C1), -12.4 [-11.0 - -13.8] at the end of the second year (C2) and -12.9 [-11.4 - -14.3] at the end of the third year (C3). Baseline and residual MMDs progressively decreased across the three cycles (    0.008): from 21.1 [19.8-22.4] to 9.6 [8.3-11.0] in C1, from 19.0 [17.4-20.5] to 9.6 [8.1-11.1] in C2, and from 15.9 [14.3-17.5] to 8.5 [6.9-10.1] in C3. At the end of C3, the 50% response rate was 38.5% (69/179) ConclusionsIn our cohort, mAbs induced a meaningful and sustained reduction in MMDs across three consecutive one-year cycles of treatment. The ITT analysis revealed a remaining high burden of disease. While confirming mAbs effectiveness in migraine prevention, these findings underscore the need for more treatment approaches and for exploring other non-CGRP dependent pathways.