Addressing unmet needs in migraine: Real-world fremanezumab effectiveness in participants of the PEARL study with at least three prior preventive treatment failures

Background: The Pan-European Real Life (PEARL) Phase 4 study evaluated real-world effectiveness and safety of fremanezumab for episodic migraine (EM) and chronic migraine (CM) prevention. This post-hoc analysis evaluated the effectiveness of fremanezumab in participants with three or more non-migraine-specific preventive treatment failures, including onabotulinumtoxinA. Methods: Baseline daily headache diary data were compared with diary data following fremanezumab initiation. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days (MMD) during the six months after fremanezumab initiation. Secondary endpoints included mean change from baseline in MMD at Months 1–12 and health-related quality of life. Safety was assessed through adverse events. Results: Of 451 participants, 398 with three or more previous preventive treatment failures were included in the effectiveness analyses (EM, 40.2%; CM, 59.8%). Of the 290 participants with data available, the 50% responder rate was 53.8% (EM, 67.0%; CM, 46.5%) during the six months after fremanezumab initiation. The safety profile was consistent with previous findings. Conclusions: This post-hoc analysis supports the effectiveness and safety of fremanezumab for migraine prevention in patients with three or more prior preventive treatment failures. These findings are consistent with those from a randomized controlled trial (RCT) in a similar population, illustrating the transferability of RCT data to real-world clinical practice. Trial registration: encepp.eu: EUPAS35111.