Analyses Underscore Erenumab’s Efficacy in Reducing Acute Headache Medication Use

Results of post hoc analyses highlight erenumab's efficacy in reducing headache medication use among migraineurs.

In patients with episodic migraine (EM) and chronic migraine (CM), treatment with erenumab was associated with a significant and sustained reduction in the use of acute headache medication, and particularly migraine-specific medication (MSM), according to results of post hoc analyses published in The Journal of Headache and Pain.

Erenumab is a fully human monoclonal antibody, first approved in 2018, and is administered monthly via self-injection of a 70- or 140-mg dose. It works to block the calcitonin gene-related peptide (CGRP) receptor, which is believed to play a crucial role in the pathophysiology of migraine.

Although many migraineurs rely on the use of acute medication for the symptomatic relief of an attack, excessive use of these treatments is of clinical concern. “The International Classification of Headache Disorders 3rd edition (ICHD-3) defines medication overuse as triptan, opioid, barbiturate, ergot alkaloid medication, or combination analgesic use on at least 10 days per month, or a nonsteroidal anti-inflammatory drug (NSAID) or simple analgesic on at least 15 days per month,” researchers wrote.

Overuse of analgesics or MSM (excluding gepants) can lead to medication overuse headache (MOH) and adverse health outcomes.

To better understand the effects of erenumab vs placebo on monthly MSM treatment days (MSMD) when restricted to those who used MSM at baseline, researchers conducted analyses of data from 2 erenumab studies on CM (n = 667) and EM (n = 955) and their extensions.

Throughout the baseline and treatment periods, patients recorded acute headache medication use via a daily electronic diary. In both studies, use of new acute headache medication could not be initiated post baseline.

“In the EM and CM studies, 60% and 78% of patients (all acute headache medication users at baseline) utilized MSM at baseline, respectively,” authors said.

Analyses revealed:

  • For acute headache medication users, the change in mean monthly acute headache medication days (HMD) over months 4, 5, and 6 compared with the pre–double-blind treatment phase (DBTP) was 1.5, 2.5, and 3.0 for placebo and erenumab 70 mg and 140 mg, respectively, for the EM study.
  • The respective change in monthly MSMD in MSM users was 0.5, 2.1, and 2.8, and in monthly non-MSMD in non-MSM users was 2.3, 2.6, and 2.7.
  • In the acute headache medication users at baseline, the change in monthly acute HMD at month 3 compared with pre-DBTP was 3.4, 5.5, and 6.5 for placebo and erenumab 70 mg and 140 mg, respectively. for the CM study.
  • The respective change in monthly MSMD in MSM users was 2.1, 4.5, and 5.4, and in monthly non-MSMD in non-MSM users was 5.9, 6.4, and 6.6.
  • Reductions in MSMD vs placebo were sustained in the extension periods of both studies.
  • Erenumab was associated with a higher proportion of MSM users achieving at least 50%, at least 75%, and 100% reduction from baseline in monthly MSMD vs placebo in both EM and CM.

“Reductions in MSMD associated with erenumab, using the entire study populations of the EM and CM studies, have been reported previously. However, given that not all patients used MSM at baseline, we performed a more relevant analysis using the subgroup of MSM users at baseline and the results reflect the expected greater effect in this subgroup,” researchers explained.

In addition, the low placebo response on the MSM endpoint can be interpreted in the light of the evidence that expectation bias may be a drive of placebo response, they added.

Previous real-world findings also supported the efficacy of erenumab in reducing acute medication use, although additional investigations beyond retrospective analyses are still needed.

Overall, “these post-hoc analyses of the EM and CM clinical studies show significant reductions in monthly acute HMD, as well as numerical reductions in non-MSMD in non-MSM only users at baseline, following erenumab treatment,” researchers concluded. “Reductions in MSMD versus placebo were maintained in the extension phases of both studies.”


Tepper SJ, Ashina M, Reuter U, et al. Reduction in acute migraine-specific and non-specific medication use in patients treated with erenumab: post-hoc analyses of episodic and chronic migraine clinical trials. J Headache Pain. Published online July 23, 2021. doi:10.1186/s10194-021-01292-w

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