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.