Likelihood of response with subsequent dosing for patients with migraine and initial suboptimal response with eptinezumab: A post hoc analysis of two placebo-controlled randomized clinical trials

Abstract

Objective: To develop a multivariable model assessing factors predicting a second-dose response to eptinezumab treatment over weeks 13-24 in patients with migraine initially reporting a suboptimal response over weeks 1-12.

Background: Eptinezumab is a monoclonal antibody used for migraine prevention, administered every 12 weeks. In the PROMISE-1 and PROMISE-2 studies, the first-dose response to eptinezumab treatment (≥50% monthly migraine day [MMD] reduction over weeks 1-12) occurred in ~50-60% of patients with episodic (EM) and chronic migraine (CM), respectively.

Methods: This post hoc analysis included patients with suboptimal first-dose response (<50% MMD reduction over weeks 1-12) with EM and CM, with patient-reported outcome data at weeks 12 and 24. Eptinezumab 100 and 300 mg doses were pooled.

Results: The analysis included 416/888 patients (46.8%) from PROMISE-1 and 479/1072 patients (44.7%) from PROMISE-2 with suboptimal first-dose response. The proportion of suboptimal first-dose responders who were second-dose responders was 37.0% (71/192; eptinezumab) and 33.9% (42/124; placebo) in PROMISE-1 and 28.8% (79/274) and 18.5% (38/205) in PROMISE-2. Significant first-dose predictors of second-dose response were percent change in MMDs across weeks 1-12 (PROMISE-1, odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.95, 0.98, p = 0.0001; PROMISE-2, OR: 0.94, CI: 0.92, 0.96, p < 0.0001) and change in 6-item Headache Impact Test (HIT-6) total score (PROMISE-2 only, OR: 0.92; CI: 0.87, 0.98; p = 0.027). In PROMISE-1, the probability of second-dose response ranged from 21.7% in patients with first-dose 0% MMD change to 56.0% in patients with first-dose 45% MMD reduction. In PROMISE-2, depending on HIT-6 total score, probability of second-dose response ranged from 5.9-12.1% in patients with first-dose 0% MMD change to 54.2%-72.3% in patients with first-dose 45.0% MMD reduction.

Conclusion: Individuals with migraine not experiencing ≥50% MMD response to their first dose of eptinezumab may benefit from a second dose.

Keywords: PROMISE-1; PROMISE-2; chronic migraine; episodic migraine; eptinezumab; response.