Benefits Observed With Second Dose of Eptinezumab in Chronic, Episodic Migraine

The percent change in monthly migraine days across weeks 1 to 12 and scores on Headache Impact Test were precursors to suboptimal response to eptinezumab, prompting the need for a second dose.

Data from a post hoc analysis of the pivotal phase 3 PROMISE-1 and -2 studies (NCT02559895; NCT02974153) of eptinezumab (Vyepti; Lundbeck) showed that a second dose of the monoclonal antibody may benefit those with suboptimal first-dose response. The results were presented at the 2022 American Headache Society (AHS) Annual Scientific Meeting, June 9-11, in Denver, Colorado, by lead investigator Jack Schim, MD, codirector, The Headache Center of Southern California.1

Respectively, in PROMISE-1 and -2, 37% (71 of 192) and 28.8% (79 of 274) of patients with a suboptimal first-dose response—defined as less than 50% monthly migraine day (MMD) reduction over 12 weeks of treatment—became second-dose responders. In comparison, 33.9% (42 of 142) and 18.5% (38 of 205) of those on placebo, respectively, experienced at least a 50% MMD response from their second dose.

The analysis specifically looked at weeks 13 to 24 of treatment with eptinezumab in patients with migraine initially reporting a suboptimal response to the therapeutic over the previous 12 weeks. Patient-reported outcome data were available at weeks 12 and 24, with both 100-mg and 300-mg dose groups pooled. In total, 46.8% (416 of 888) and 44.7% (479 of 1072) of those in PROMISE-1 and -2 had suboptimal first-dose response and were thus included in the analysis.

READ MORE: Rimegepant is Well-Tolerated and Safe for Migraine Over 1 Year With Every-Other-Day Dosing

Using full logistic regression models, 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% CI, 0.95; 0.95-0.98]; P = .0001; PROMISE-2: OR, 0.94 [95% CI, 0.92-0.96]; P <.0001) and change in 6-item Headache Impact Test (HIT-6) total score (PROMISE-2: OR, 0.92; 95% CI, 0.87-0.98; P = .0269). Schim et al noted that the probability of second-dose response for those in PROMISE-2 ranged from 21.7% in individuals with first-dose 0% MMD change to 56.0% in patients with first-dose 45% MMD reduction.

In PROMISE-2, for those with first-dose 0% MMD change, the probability of second-dose response, dependent on HIT-6 total score, ranged from 5.9% to 12.1%, compared with a range of 54.4% to 72.3% for patients with a first-dose MMD reduction of 45%. Eptinezumab, a humanized monoclonal antibody that binds to calcitonin gene-related peptide ligand and blocks its binding to the receptor, received FDA approval in February 2020 for the prevention of migraine in adults, with a recommended dose of 100 mg to be administered quarterly.

At the 2021 AHS Annual Scientific Meeting, data from PROMISE-2 showed that patient response within the first month is predictive of sustained response to treatment for patients with chronic migraine. Ultimately, the majority of patients in the trial (total, n = 1072; 100 mg, n = 356; 300 mg, n = 350; placebo, n = 366) randomized to one of the dosing groups of eptinezumab responded well to treatment within the first month (≥50% responder rates: 100 mg, 54.5% [n = 194]; 300 mg, 60.6% [n = 212]; placebo, 36.1% [n = 132]). Of those, 30.9% (n = 110) in the 100-mg group and 36.9% (n = 129) in the 300-mg group reported at least 75% responder rates, compared to 15.6% (n = 57) of the placebo group.2

In a recent NeurologyLive® Peer Exchange titled “Optimal Management of Acute and Preventive Migraine,” experts including Andrew C. Charles; Bradley Torphy, MD; and Jessica Ailani, MD, reviewed current FDA-approved CGRP monoclonal antibodies available for the preventive treatment of migraine, including eptinezumab.

Click here for more coverage of AHS 2022.

1. Schim JD, Anderson C, Brunner E, et al. Likelihood of response with subsequent dosing for patients with migraine and initial suboptimal response with eptinezumab. Presented at: AHS Annual Scientific Meeting; June 9-11, 2022; Denver, CO. P-180.
2. Buse DC, Winner PK, Charleston L, Hirman J, Cady R, Brevig T. Early Response to Eptinezumab Indicates High Likelihood of Continued Response with Treatment in Patients with Chronic Migraine. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P200.