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.
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.