Study Analyzes Effects of Erenumab Based on MMD Reduction Threshold

August 31, 2020

Using data from the Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention, researchers were able to analyze the efficacy of erenumab at ≥50%, ≥75%, and 100% thresholds for reduction in monthly migraine days.

Using data from the Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention (STRIVE), researchers were able to analyze the efficacy of erenumab at ≥50%, ≥75%, and 100% thresholds for reduction in monthly migraine days (MMD).

Erenumab, which was approved by the FDA in 2018, is a calcitonin gene-related peptide (CGRP) inhibitor administered via self-injection once a month. The treatment blocks the CGRP receptor, which is believed to play a crucial role in migraine. Erenumab can be injected as a 70- or 140-mg dose in adults with migraine.

The findings will be used to provide context for establishing realistic patient and physician expectations regarding the magnitude of treatment benefit that could be achieved by patients with episodic migraine (EM) responding to erenumab, authors wrote. Results were published in Headache: The Journal of Head and Face Pain.

All patients with EM, defined as ≥4 and <15 migraine days per month and <15 headache days per month, were randomized (1:1:1) to placebo (n = 316), 70 mg of erenumab (n = 312) or 140 mg of erenumab (n = 318). Participants used an electronic diary to record daily information about migraine and non-migraine headaches, use of migraine-specific abortive therapies, and use of analgesic medications.

“Mean MMD were calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24‐week double-blind treatment phase (if at least 1 MMD was present)” of STRIVE, researchers wrote.

Analyses revealed:

  • Proportions of patients with a reduction in MMD from baseline were greater for erenumab than for placebo at all response thresholds
  • For the ≥50% response threshold, 135/312 (43.3%) of patients on erenumab 70 mg and 159/318 (50.0%) on erenumab 140 mg responded, vs 84/316 (26.6%) for placebo
  • At months 4-6, 65/312 (20.8%) and 70/318 (22.0%) of those on erenumab 70 mg and erenumab 140 mg, respectively, achieved ≥75% reductions vs 25/316 (7.9%) on placebo
  • A reduction of 100% response, which required no migraine days over 3 consecutive months, was achieved by 10/312 (3.2%) of patients treated with erenumab 70 mg and 16/318 (5.0%) for erenumab 140 mg, vs 9/316 (2.8%) for placebo
  • At all thresholds, responders achieved numerically greater reductions in mean MMD and migraine-specific medication days, and greater improvements in disability than did the overall population
  • 60/312 (19.2%) and 53/318 (16.7%) patients on erenumab 70 and 140 mg, respectively, had no reduction in MMD from baseline in months 4-6, compared with 104/316 (32.9%) patients on placebo
  • Patients who achieved responses at the ≥50%, ≥75%, or 100% thresholds displayed substantial improvement in migraine‐related disability and headache impact compared with the overall erenumab‐treated population

“Erenumab treatment effect at the ≥75% and 100% response thresholds was already visible by month 1…and the proportions of patients responding increased over the first 3 months and were sustained thereafter, albeit with some month‐to‐month variation in response,” authors wrote.

Month-to-month variation was not observed at the ≥50% response threshold and authors hypothesize this may be due in part to the lower number of patients achieving ≥75% and 100% responses. To better understand how high-level responses are distributed among patients future studies could divide the 100% threshold into smaller ranges.

In addition, authors noted the lack of response in some patients “raises the possibility that there may be as yet undefined migraine subtypes in which the CGRP pathway may not play a prominent role in the generation and pathogenesis of their migraine attack.” This finding demonstrates that subjects who do not achieve MMD responses at a certain threshold may still be deriving treatment benefit.

“However, the effects of these factors, which may include baseline characteristics, underlying pathophysiology, and genetics, among others, on response are not understood,” researchers wrote. “Therefore, there is no way at present to predict the level of response that a patient will experience, which represents an important gap in our knowledge.”

The current study was funded by Amgen, which co-develops erenumab with Novartis.

Reference

Broessner G, Reuter U, Bonner JH, et al. The spectrum of response to erenumab in patients with episodic migraine and subgroup analysis of patients achieving ≥50%, ≥75%, and 100% response. Headache. Published online August 26, 2020. doi:10.1111/head.13929