PO-91 | Real-world evidence of CGRP dual blockade: clinical and biomarker insights from combined therapy in chronic migraine

Background: This observational study presents preliminary real-world evidence on the comparative efficacy and safety of combination therapy with onabotulinumtoxinA and the CGRP receptor antagonist atogepant versus atogepant monotherapy in patients with treatment-refractory chronic migraine. Methods: Twenty adult patients (aged 18-75) meeting ICHD-3 criteria for refractory chronic migraine - defined by 8 monthly migraine days, MIDAS ³11, and inadequate response or intolerance to ³ 3 preventive therapies - were enrolled. Ten patients received atogepant monotherapy, while ten initiated combination therapy with onabotulinumtoxinA and atogepant. Efficacy was assessed over three months using changes in monthly migraine days, headache severity (Numerical Rating Scale, NRS), and disability scores (HIT-6, MIDAS). Acute medication use and tolerability were also evaluated. Results: The combination therapy group demonstrated significantly greater reductions in monthly migraine days, headache intensity, and disability scores compared to the monotherapy group. Responders - defined as patients remaining migraine-free for ³6 consecutive weeks - were more frequent in the combination cohort. Both treatments were well tolerated, with no serious adverse events reported. Chronic migraine remains a debilitating condition, often resistant to standard preventive treatments. Dual blockade of the CGRP pathway - via onabotulinumtoxinA and a CGRP receptor antagonist - may offer synergistic benefits by targeting both peripheral and central CGRP mechanisms. Conclusion: These preliminary findings support the enhanced clinical efficacy and safety of combining onabotulinumtoxinA with CGRP receptor antagonists in managing refractory chronic migraine. This multimodal strategy may provide a personalized, mechanism-based approach to care and warrants further investigation in larger, controlled studies.