Preventive migraine treatment with eptinezumab reduced acute headache medication and headache frequency to below diagnostic thresholds in patients with chronic migraine and medication-overuse headache

Abstract

Objective: This post hoc analysis in patients medically diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) evaluated reductions in the use of acute headache medication (AHM) and sustained changes in the diagnostic status of CM and MOH following eptinezumab treatment in the PROMISE-2 study.

Background: Eptinezumab, a monoclonal antibody that inhibits calcitonin gene-related peptide, is approved in the United States for the preventive treatment of migraine. A previous analysis showed that eptinezumab reduced monthly migraine days and was well tolerated in the subgroup of PROMISE-2 patients diagnosed with both CM and MOH.

Methods: The phase 3, double-blind, placebo-controlled PROMISE-2 study (NCT02974153) randomized adults with CM to eptinezumab 100 mg, 300 mg, or placebo (administered intravenously every 12 weeks for up to two doses). MOH was prospectively diagnosed at screening by trained physicians based on 3 months of medication history and International Classification of Headache Disorders-3β criteria. This post hoc analysis evaluated changes in total and class-specific days of AHM usage, the percentage of patients using AHM at or above MOH diagnostic thresholds, and the percentage of patients experiencing monthly headache and migraine day frequency below diagnostic thresholds for MOH and/or CM.

Results: In PROMISE-2, 431/1072 (40.2%) patients with CM were diagnosed with MOH (eptinezumab 100 mg, n = 139; 300 mg, n = 147; placebo, n = 145) and were included in this analysis. Total monthly AHM use decreased from 20.6 days/month at baseline to 10.6 days/month over 24 weeks of treatment (49% decrease) with eptinezumab 100 mg, from 20.7 to 10.5 days/month (49% decrease) with eptinezumab 300 mg, and from 19.8 to 14.0 days/month (29% decrease) with placebo. Numerically greater decreases from baseline with eptinezumab were also observed for individual drug classes. In each study month, the percentages of patients who were below MOH thresholds were numerically higher for both eptinezumab doses compared with placebo, as were the percentages of patients experiencing headache and migraine frequency below CM thresholds. Of patients with available data across the entire treatment period, 29.0% (58/200) of patients treated with eptinezumab stopped meeting and remained below diagnostic thresholds for both CM and MOH during Weeks 1-24, as well as 6.3% (6/96) of patients who received placebo.

Conclusions: Across 24 weeks of treatment, eptinezumab reduced AHM use in patients diagnosed with CM and MOH. More than one-fourth (29%) of patients treated with eptinezumab did not meet the diagnostic thresholds for either CM or MOH for the entire treatment period.

Keywords: acute headache medication use; chronic migraine; eptinezumab; medication-overuse headache.

FIGURE 1

Mean days/month of total^a acute headache medication use. ^aTotal acute headache medication days is the sum of triptan, ergotamine, opioid, simple analgesic, and combination analgesic days of use. If a patient used two classes of medication on the same day, they were counted twice. SE, standard error

FIGURE 2

Mean days/month of acute headache medication use by class, in patients with any of that class during baseline. (A) Triptan use. Analysis includes patients who reported ≥1 day of triptan use during the 28‐day screening period. Sample sizes at baseline: eptinezumab 100 mg, n = 92; eptinezumab 300 mg, n = 112; placebo, n = 105. (B) Simple analgesic use. Analysis includes patients who reported ≥1 day of simple analgesic use during the 28‐day screening period. Sample sizes at baseline: eptinezumab 100 mg, n = 101; eptinezumab 300 mg, n = 95; placebo, n = 98. (C) Combination analgesic use. Analysis includes patients who reported ≥1 day of combination analgesic use during the 28‐day screening period. Sample sizes at baseline: eptinezumab 100 mg, n = 64; eptinezumab 300 mg, n = 79; placebo, n = 63. SE, standard error

FIGURE 3

Rates of medication overuse in patients with chronic migraine and medication‐overuse headache (MOH), by study month. Medication overuse was defined by MOH thresholds in the ICHD‐3β criteria (including section 8.2.6). Classes of medication included triptan, ergot, opioid, simple analgesic, and combination analgesic, and were counted separately for days of use; simple analgesics were counted separately as ≥15 days/month

FIGURE 4

Patients experiencing below chronic migraine (CM) thresholds by study month. CM diagnostic thresholds were defined as ≥15 headache days/month and ≥8 migraine days/month per ICHD‐3β criteria

FIGURE 5

Percentage of patients who did not experience chronic migraine (CM) nor medication‐overuse headache (MOH) thresholds for an entire dosing interval. Subgroup includes patients with MOH who reported headache and migraine days below CM thresholds, as well as acute medication use below MOH thresholds, for each individual study month within the respective dosing interval. Medication overuse was defined by MOH thresholds in the ICHD‐3β criteria (including section 8.2.6). Classes of medication included triptan, ergot, opioid, simple analgesic, and combination analgesic, and were counted separately for days of use; simple analgesics were counted separately as ≥15 days/month. CM diagnostic thresholds were defined as ≥15 headache days/month and ≥8 migraine days/month per ICHD‐3β criteria