PO-52 | Long-term efficacy of CGRP mAbs: new insights and current evidence

Oreste Marsico,¹ Marta Lioi,² Rosario Iannacchero,³ Michele Trimboli³ | ¹Department of Neuroscience, “Giovanni Paolo II” Hospital, Lamezia Terme, Catanzaro, Italy; ²Department of Neurology, Magna Graecia University, Catanzaro, Italy; ³Institute of Neurology, AOU Renato Dulbecco, Catanzaro, Italy

Background: Anti-CGRP monoclonal antibodies (mAbs) have proven effective and well-tolerated for migraine prevention. Most clinical trials assess treatment response at 3 months. However, emerging real-world evidence indicates that a meaningful proportion of migraine patients may require extended treatment durations to achieve clinical improvement. In this narrative review, we examined the prevalence, potential mechanisms, and clinical significance of delayed responses to anti-CGRP therapies, with a focus on late (3-6 months) and ultra-late (6-12 months) responders.

Methods: An extensive literature review was conducted to analyze data from real-world studies investigating delayed responses to anti-CGRP mAbs or receptor antagonists in patients with episodic and chronic migraine. Treatment response was defined as a ≥30% or ≥50% reduction in monthly migraine days. Late and ultra-late responders were identified among patients who did not meet this threshold at 3 months but subsequently achieved it at 6 or 12 months, respectively.

Results: We identified 10 real-world studies examining delayed responses to anti-CGRP mAbs, most of which had a retrospective and observational design. Across all the studies, the mean rate of late responders was around 16%, while the rate of ultra-late responders was 15.7%, as highlighted by only one study. If we consider the patients who did not respond at 3 months, about one-third of them showed a clinical response by 6 months, and up to two-thirds by 12 months. These findings highlight the existence of a substantial subgroup of migraine patients who may benefit from extended treatment despite an initial lack of response. Several studies also identified potential clinical predictors of late response, including chronic migraine, high body mass index, multiple prior treatment failures, longer duration of medication overuse, psychiatric comorbidities, a higher number of comorbidities, unilateral pain, unilateral cranial autonomic symptoms, and cutaneous allodynia.

Conclusion: Real-world evidence highlights the need to extend the treatment duration of anti-CGRP therapies beyond 3 months in selected migraine patients, defined as late or ultra-late responders. Prompt identification of this clinical phenotype can support more personalized and time-sensitive treatment strategies, improving long-term outcomes in migraine population.