Evaluation of the impact of migraine type (episodic or chronic; EM, CM), number of prior preventive treatment failures and treatment pauses on the reduction of monthly migraine days (MMD) induced by fremanezumab treatment among adults enrolled in the 24-month, observational, prospective, Phase 4 PEARL study.

Typically, drug reimbursement criteria limit the use of calcitonin gene-related peptide pathway monoclonal antibodies to individuals for whom multiple non-migraine-specific preventive treatments have failed, and mandate a pause in treatment after one year of continuous use. Evidence on the impact of these restrictions on treatment outcomes for individuals with migraine is limited.

The primary endpoint of the PEARL study was the proportion of participants with EM or CM achieving ≥50% reduction in MMD during the 6-month period after fremanezumab initiation. Further analyses evaluated the impact of migraine type (EM, CM) and prior preventive treatment failures (0–2 or ≥3) on the ≥50% responder rate (post-hoc), and the impact of pausing fremanezumab on MMD among participants with documented treatment cessation and reinitiation.

Of 1140 participants enrolled, 1129 were included in the effectiveness analysis: 56.5% (637/1128) achieved ≥50% reduction in MMD during the 6-month period after fremanezumab initiation. A reduction of ≥50% in MMD was achieved in 68.4% of participants with EM and 0–2 treatment failures (n = 106/155), compared with 50.5% of participants with CM and ≥3 treatment failures (n = 257/509); this trend was sustained over 24 months. Among 295 participants with documented fremanezumab cessation and reinitiation, mean MMD decreased from 9.6 at baseline of reinitiation to 6.8 at Month 1 and 6.1 at Month 3 after reinitiation, both values remaining higher than before treatment discontinuation (5.9).

These analyses suggest that optimal treatment efficacy occurs when fremanezumab is initiated early, prior to failure of multiple other preventive treatments, and is sustained without interruption.