Long-term real-world effectiveness and safety of fremanezumab in 1140 patients with migraine and at least 6 months of treatment: third interim analysis of the pan-European PEARL study.

Introduction Real-world data on the long-term use of fremanezumab for migraine prevention remain limited. This third interim analysis of the PEARL study addresses this gap by investigating the long-term effectiveness, safety, and tolerability of fremanezumab for up to 12 months of treatment. Methods PEARL is a 24-month, prospective, observational, Phase 4 study conducted in 11 European countries. Eligible participants were adults (≥ 18 years) diagnosed with chronic or episodic migraine who received subcutaneous fremanezumab (225 mg monthly or 675 mg quarterly) and completed ≥ 6 months of treatment. The primary endpoint was defined as the proportion of participants achieving a ≥ 50% reduction in monthly migraine days (MMD) during the 6-month period following treatment initiation. Secondary endpoints included mean change from baseline to Month 12 in: average MMD, acute migraine medication use, and migraine-related disability scores, as measured by the Migraine Disability Assessment and the 6-item Headache Impact Test. Safety was assessed through the collection of adverse events. Results At data cut-off (22 September 2022), 968 of 1140 enrolled participants were included in the effectiveness analysis with 58.5% achieving the primary endpoint. Sustained reductions in MMD, acute medication use, and disability scores were observed over 12 months, and no new safety signals were detected. Conclusions Findings from this third interim analysis of PEARL provide compelling evidence for the long-term effectiveness of fremanezumab in a large, real-world patient population. The results support the continued use of fremanezumab as a preventive strategy for migraine and underscore the value of integrating real-world evidence into migraine management.Trial Registration Number EUPAS35111.