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. 2022 May;62(5):558-565.
doi: 10.1111/head.14302. Epub 2022 May 6.

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

Jack D Schim  1 , Carlton Anderson  2 , Elizabeth Brunner  2 , Joe Hirman  3 , Annette Ogbru  2 , Roger Cady  2 , Lora McGill  4
Affiliations

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

Jack D Schim et al. Headache. 2022 May.

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.

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Conflict of interest statement

LM has served as a consultant, advisory board member, and/or speaker for Abbvie, AEVI, Alkermes, Allergan, Amgen, Aptinyx, Arbor, Axsome, AZTherapies, Bayer, Biogen, Biohaven, Bionomics, BlackThorn, CoLucid, Daiichi Sankyo, Dr. Reddy's, Eli Lilly, Esperion, Intarcia, Intra‐Cellular, Ironshore, Janssen, Labrys Biologic, Lundbeck, Mitsubishi, Mylan, NLS Pharma, Nektar, Nestle Pamlab, Neuralstem, Neurocrine, Novartis, Novo Nordisk, ObsEva, Otsuka, Palatin, Pfizer, Regeneron, Rhodes, Shionogi, Shire, Sunovion, Supernus, Takeda, TauRx, and Teva. JDS has served on advisory boards for Aeon, Allergan, Amgen, Biohaven, electroCore, Impel, Lilly, Lundbeck, Novartis, Promius, Revance, Teva, and Upsher‐Smith; and has received compensation for speaking from Allergan, Amgen, Biohaven, electroCore, Eli Lilly, Lundbeck, Novartis, Promius, Teva, and Upsher‐Smith. CA, EB, and AO are full‐time employees of H. Lundbeck A/S or one of its subsidiary companies. RC was an employee of Lundbeck or one of its subsidiary companies at the time of study and manuscript development. JH is an employee of Pacific Northwest Statistical Consulting, Inc., a contracted service provider of biostatistical resources for H. Lundbeck A/S.

Figures

FIGURE 1
FIGURE 1
Percentage of patients with ≥50% migraine response by weeks 1–12 and weeks 13–24 and treatment group in (A) PROMISE‐1 (episodic migraine) and (B) PROMISE‐2 (chronic migraine)
FIGURE 2
FIGURE 2
Difference in monthly migraine days between infusion 1 (weeks 1–12) and 2 (weeks 13–24) for infusion 1 non‐responders by study (PROMISE‐1, episodic migraine; PROMISE‐2, chronic migraine). MMD, monthly migraine days
FIGURE 3
FIGURE 3
Probability (with 95% confidence interval) of second‐infusion (weeks 13–24) ≥50% monthly migraine day response based on first‐infusion (weeks 1–12) predictors in the PROMISE‐1 study (episodic migraine). EM, episodic migraine; MMD, monthly migraine days
FIGURE 4
FIGURE 4
Probability (with 95% confidence interval) of second‐infusion (weeks 13–24) ≥50% monthly migraine day response based on first‐infusion (weeks 1–12) predictors in the PROMISE‐2 study (chronic migraine), for (A) 6‐item Headache Impact Test (HIT‐6) change =0, (B) HIT‐6 change = –6, (C) HIT‐6 change = –10. CM, chronic migraine; MMD, monthly migraine days
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