Background <p>The CGRP pathway targeting antibody fremanezumab is indicated for prevention of migraine in adults with ≥4 migraine days/month. To address the limited availability in real-world long-term data, the FINESSE study was initiated to provide real-world evidence of long-term effectiveness of fremanezumab in clinical practice in an unselected migraine patient cohort.</p> Methods <p>FINESSE was a non-interventional, prospective, multicentre, two-country (Germany, Austria) study observing migraine patients receiving fremanezumab over 24 months in clinical routine. The primary endpoint was the proportion of patients reaching ≥50% reduction in the monthly average number of migraine days (MMD) during the 6-month period following fremanezumab initiation. Secondary endpoints included changes from baseline in MMD, MIDAS and HIT-6 scores, and use of concomitant acute migraine medication. Exploratory endpoints comprised assessment of number and classes of concomitant preventive and acute migraine medications, and reduction in migraine severity. All secondary and exploratory outcomes were evaluated at multiple timepoints over the 24-month observation period. Safety data were obtained based on documentation of adverse events reported in normal clinical practice. Data analysis was performed using descriptive and, for comparisons to baseline, inferential statistics.</p> Results <p>Data of 1016 patients (88.7% female; mean age 45.7 (SD 12.4); 55% episodic migraine; 45% chronic migraine) were evaluable in the full analysis set. Out of 987 patients in the primary endpoint set, the proportion of responders with a ≥ 50% MMD reduction during the 6-month period following fremanezumab initiation was 52.8% in all patients, 57.0% in episodic and 47.8% in chronic migraine patients. Further benefit was observed in terms of clinically meaningful MMD reductions from baseline, decrease in the use of concomitant acute medication, migraine severity, and improvements in disability scores, which were sustained over the 24-month observation period. No new safety signals were identified.</p> Conclusions <p>Long-term fremanezumab treatment was associated with rapid, substantial and sustained improvement in both episodic and chronic migraine in a high proportion of patients in a real-world setting throughout the 24-month observation period. Real-world-data on tolerability corroborate the expected favourable safety profile of fremanezumab demonstrated in the pivotal clinical trials.</p> Trial registration <p>The FINESSE study was retrospectively registered on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS44606) on December 8, 2021, and previously registered at Paul-Ehrlich-Institut (Federal Institute for Vaccines and biomedicines) on November 11, 2019. </p> Graphical Abstract <p></p>