Study participants with medication overuse headache reported quality of life improvements as early as study week 4 that were sustained at week 24.
In adults with chronic migraine (CM) and medication-overuse-headache (MOH), eptinezumab was associated with clinically meaningful and rapid improvements in headache-related life impact.
The data, from a subgroup analysis of the phase 3 PROMISE-2 study, also showed that initiating preventive migraine treatment with eptinezumab can improve outcomes in this patient population even if they are not instructed to wean off of or stop using acute medications.
MOH is a prevalent and prominent secondary headache disorder commonly associated with CM, wrote authors led by Amaal J. Starling, MD, assistant professor of Neurology, Concussion, and Headache Medicine divisions, Mayo Clinic. It is associated with higher rates of disease impact, medical cost, and disability then CM alone. Eptinezumab, a calcitonin gene-related peptide (CGRP) inhibitor, is indicated for prevention of migraines in adults and given by IV infusion every 12 weeks.
In 2 previous post-hoc analyses of the PROMISE-2 study, eptinezumab was found safe and effective in the subgroup with CM/MOH but neither study discussed self-reported patient outcomes that would “capture the effect of treatment on migraine burden,” said Starling, et al, writing in the journal Headache. Starling and colleagues set out to do that, assessing the impact of eptinezumab on patient-reported outcomes related to disease severity, disease burden, and HRQoL in the PROMISE-2 participants with CM/MOH.
The subgroup analysis included 139, 147, and 145 patients randomly assigned to eptinezumab 100 mg, 300 mg, and placebo groups. Starling and her team aimed to evaluate the effect of eptinezumab as a sole variable on 4 specific patient-reported outcomes: the 6-Item Headache Impact Test (HIT-6), the Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36).
Participants received up to 2 doses of the study drug or placebo, each 12 weeks apart, for a 24-week treatment period. Investigators provided no education on MOH and did not instruct participants to reduce use of their acute medications, presumably the cause of MOH.
Among the 431-participant cohort, the mean age was 41.4 years, and the majority were women (87.2%) and White (9.35%). At baseline, the mean number of acute medication use days/month was 16; 87.5% of patients reported migraine having severe life impact based on HIT-6 total score. Mean SF-36 scores at baseline showed impairments on scores for bodily pain and reduced function in physical and social functioning domains.
The investigators reported that both doses of eptinezumab were associated with improvements in mean HIT-6 total score at study week 24. Following a baseline score of 65.1 (standard deviation [SD], 5.4), participants in the 100 mg group saw a reduction to 57.5 (SD, 7.9); in the 300 mg group, the baseline score of 65.0 (SD, 4.9) fell to 56.0 (SD 8.6). The improvements, according to Starling et al, were significant as early as the fourth week of treatment and were sustained for the 24-week study period.
The researchers emphasized that the majority of participants (87-88%) in all 3 study groups reported at baseline that their migraines had a severe impact on life. By week 24, the proportion of patients with severe headache impact had declined substantially to 39.5%, 38.6%, and 65.5% in the eptinezumab 100 mg, 300 mg, and placebo groups, respectively.
At weeks 12 and 24, nearly double the number of eptinezumab-treated participants reported improvements on the PGIC vs those receiving placebo. Likewise, both eptinezumab groups reported substantial improvements in PI-MBS and SF-36 scores over the course of the study vs the placebo group.
"MOH management can be challenging for patients and providers," Starling et al wrote. "Based on this study, the first step should include preventive treatment that will reduce migraine frequency and, as other literature suggests, potentially include patient education of the negative effects of increased use of acute medications and the existence of MOH or ‘rebound headaches.’
"If the reduction in the number of headache/migraine days is the main treatment goal in managing CM with MOH, a patient may not need to switch or limit their overused medication in order to achieve positive outcomes."
Among this study’s limitations the authors note that opioid and barbiturate use was limited to only 4 days per month during the screening period, excluding those who have exceeded the limit. Additionally, a large placebo response was observed, which is common in migraine treatment studies; however, the placebo response was lower in patients with MOH relative to the overall PROMISE-2 population.
Reference: Starling AJ, Cowan RP, Buse DC, et al. Eptinezumab improved patient-reported outcomes in patients with migraine and medication-overuse headache: Subgroup analysis of the randomized PROMISE-2 trial. Headache. Published online January 12, 2023. doi:10.1111/head.14434