by Jessica Ailani, MD, FAHS, FAAN

The speed of onset of therapy for migraine is an important factor for patients. In a 2007 study by Peres et al, speed of onset was the second most important factor in a preventive treatment behind efficacy (1). This study, by Dodick et al, evaluated efficacy of eptinezumab the first day after dosing for episodic or chronic migraine. Eptinezumab is an intravenous (IV) calcitonin gene related peptide (CGRP) monoclonal antibody that binds to the CGRP ligand and is FDA approved for migraine prevention (2,3). At a dose of 100mg, after a single IV administration over 30 minutes, Cmax (37.3 μg ml) is reached at a Tmax of 30 minutes (4). The pharmacokinetic (pk) data suggests the possibility of rapid onset of treatment. This study looks to answer the question, can eptinezumab have clinical results that mirror its pk data?

This study was a post hoc analysis of the phase 3, double-blind, randomized, placebo-controlled trials evaluating efficacy of eptinezumab as a preventive treatment for episodic and chronic migraine. The study evaluated the percentage of patients with a migraine on Day 1 after IV treatment with eptinezumab, hoping to see if this measures full preventive effect. The study used a post-hoc closed testing procedure to analyze the proportion of patients who experienced a migraine in progressively smaller time intervals from days 1 to 84. Starting from day 84, an evaluation was done looking at how many patients had migraine during a specific interval. If the value was statistically significant, the interval was reduced by 1 day and effect was tested again. The results found that a greater portion of patients were migraine free day 1 after infusion when treated with eptinezumab 100mg or 300mg compared to placebo. This response was sustained for 12 weeks.

This study provides clinicians exciting news to share with patients who are considering eptinezumab for treatment of migraine. It also aids clinicians with more data to assist with making decisions about when to consider use of eptinezumab compared to another CGRP monoclonal antibody. If a patient needs results as soon as day 1 (for example, threat of loss of work, considering hospitalization to break a migraine cycle), this study supports the option of eptinezumab for rapid results. For patients, having data on a medication to support fast onset results allows them more information when making treatment decisions, especially when considering an IV therapy as opposed to a therapy they can administer to themselves at home.

 

References:

1. Peres MFP, Silberstein S, Moreira F, et al. (2007). Patients' preference for migraine preventive therapy. Headache: The Journal of Head and Face Pain, 47(4), 540-545.
2. Ashina M, Saper J, Cady R, et al. (2020). Eptinezumab in episodic migraine: a randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia, 40(3), 241-254.
3. Lipton RB, Goadsby PJ, Smith J (2020). Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology, 94(13), e1365-e1377.
4. Baker B, Schaeffler B, Beliveau M, et al. (2020). Population pharmacokinetic and exposure‐response analysis of eptinezumab in the treatment of episodic and chronic migraine. Pharmacology Research & Perspectives, 8(2), e00567.