Measuring dose-related efficacy of eptinezumab for migraine prevention: post hoc analysis of PROMISE-1 and PROMISE-2

Abstract

Background: Eptinezumab 100 mg and 300 mg met the primary efficacy endpoint in both PROMISE clinical trials, significantly reducing frequency of monthly migraine days over Weeks 1‒12. The objective of this analysis was to assess the clinical response to eptinezumab 100 mg and 300 mg within the pivotal phase 3 PROMISE-1 and PROMISE-2 studies to potentially identify subsets of patients with meaningful differences between doses.

Methods: Patients from PROMISE-1 (NCT02559895) and PROMISE-2 (NCT02974153) trials were divided into subgroups based on demographic and migraine characteristics, and baseline questionnaire responses. For each subgroup, the overall likelihood of achieving ≥ 50% migraine responder rate (MRR) over Weeks 1-12 and Weeks 13-24 with either eptinezumab 100 mg or 300 mg was calculated using odds ratios (with associated confidence intervals) and compared.

Results: In PROMISE-1 (episodic migraine) and PROMISE-2 (chronic migraine), the likelihood of achieving ≥ 50% MRR over Weeks 1-12 and Weeks 13-24 was roughly equivalent for patients receiving either dose level of eptinezumab. Given the number of comparisons performed, sporadic apparent differences were seen but no replicated patterns between studies emerged. In PROMISE-1, no differences were observed in any subgroup over Weeks 1-12. In PROMISE-2, patients reporting < 15 monthly migraine days at baseline, any problems with mobility per the EQ-5D-5L, or a social functioning score > 45.0 per the 36-item Short-Form Health Survey (SF-36), appeared more likely to achieve ≥ 50% MRR with 300 mg over Weeks 1-12, with none of these being apparent in PROMISE-1.

Conclusions: Overall, these data suggest that across PROMISE-1 and PROMISE-2, there were no meaningful differences in the likelihood of achieving ≥ 50% MRR between the eptinezumab dose levels in the majority of patient subgroups. In the few subgroups that displayed small, but potentially meaningful differences, patients were more likely to achieve ≥ 50% MRR with eptinezumab 300 mg; however, minimal consistency across both studies and time periods was noted.

Trial registration: ClinicalTrials.gov. PROMISE-1: NCT02559895 . PROMISE-2: NCT02974153 .

Keywords: Dose response; Eptinezumab; Migraine; Patient subgroups.

Conflict of interest statement

R. Apelian is a member of the speaker bureau for Lundbeck; advisor/consultant/speaker for Allergan/Abbvie, Biohaven, and Eli Lilly.

L. Boyle and D. Asher are full-time employees of Lundbeck.

J. Hirman is an employee of Pacific Northwest Statistical Consulting, Inc., a contracted service provider of biostatistical resources for Lundbeck.

© 2022. The Author(s).

Figures

Fig. 1

Odds ratio of ≥ 50% MRR over Weeks 1‒12 in PROMISE-1 subgroups defined by baseline demographics and patient-reported outcome measures. CI, confidence interval; EQ-5D-5L, EuroQol 5-dimension, 5-level scale; MHDs, monthly headache days; MMDs, monthly migraine days; MRR, migraine responder rate; N/A, not applicable (sample size too small); OR, odds ratio; SF-36, 36-item Short-Form Health Survey

Fig. 2

Odds ratio of ≥ 50% MRR over Weeks 1‒12 in PROMISE-2 subgroups defined by baseline demographics and patient-reported outcome measures. CI, confidence interval; EQ-5D-5L, EuroQol 5-dimension, 5-level scale; HIT-6, 6-item Headache Impact Test; MHDs, monthly headache days; MMDs, monthly migraine days; MRR, migraine responder rate; OR, odds ratio; PI-MBS, patient-identified most bothersome symptom; SF-36, 36-item Short-Form Health Survey

Fig. 3

Odds ratio of ≥ 50% MRR over Weeks 13‒24 in PROMISE-1 subgroups defined by baseline demographics and patient-reported outcome measures. CI, confidence interval; EQ-5D-5L, EuroQol 5-dimension, 5-level scale; MHDs, monthly headache days; MMDs, monthly migraine days; MRR, migraine responder rate; N/A, not applicable (sample size too small); OR, odds ratio; SF-36, 36-item Short-Form Health Survey

Fig. 4

Odds ratio of ≥ 50% MRR over Weeks 13‒24 in PROMISE-2 subgroups defined by baseline demographics and patient-reported outcome measures. CI, confidence interval; EQ-5D-5L, EuroQol 5-dimension, 5-level scale; HIT-6, 6-item Headache Impact Test; MHDs, monthly headache days; MMDs, monthly migraine days; MRR, migraine responder rate; PI-MBS, patient-identified most bothersome symptom; OR, odds ratio; SF-36, 36-item Short-Form Health Survey