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

Abstract

Background: In patients with migraine, overuse of acute medication, including migraine-specific medication (MSM) such as triptans and ergots, can lead to adverse health outcomes, including development of medication overuse headache. Here, we examined the effect of erenumab on reducing acute medication use, in particular MSM, in patients with episodic migraine (EM) and chronic migraine (CM).

Methods: The current post-hoc analyses were based on data from the double-blind treatment phase (DBTP) of two erenumab studies, a pivotal EM (N = 955) and a pivotal CM (N = 667) trial, and their respective extensions. Patients were administered subcutaneous placebo or erenumab (70 or 140 mg) once monthly. Daily acute headache medication use (including MSM and non-MSM) was recorded using an electronic diary during a 4-week pretreatment baseline period until the end of the treatment period. Outcome measures included change in monthly acute headache medication days (HMD) in acute headache medication users at baseline, and changes in monthly MSM days (MSMD) in MSM users at baseline and non-MSMD in non-MSM users at baseline.

Results: In total, 60 and 78 % of patients (all acute headache medication users) with EM and CM used MSM at baseline, respectively. For acute headache medication users, the change in mean monthly acute HMD over Months 4, 5 and 6 compared with the pre-DBTP was 1.5, 2.5, and 3.0 for placebo, 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, 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 versus placebo were sustained in the extension periods of both studies. Erenumab was also associated with a higher proportion of MSM users achieving ≥ 50 %, ≥ 75 and 100 % reduction from baseline in monthly MSMD versus placebo in both EM and CM.

Conclusions: In both EM and CM, treatment with erenumab is associated with a significant and sustained reduction in the use of acute headache medication, in particular MSM.

Trial registrations: NCT02456740; NCT02066415; NCT02174861.

Keywords: CGRP receptor; Chronic migraine; Episodic migraine; Erenumab; Migraine-specific.

Conflict of interest statement

SJT was an employee of the Cleveland Clinic during this study. He reports research grants (no personal compensation) from Allergan, Amgen Inc., ElectroCore, Eli Lilly, eNeura, Neurolief, Novartis, Scion Neurostim, Teva, and Zosano; consultant fees from Acorda, Aeon, Alexsa, Align Strategies, Allergan, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, Charleston Labs, CRG, Currax, Decision Resources, DeepBench, Eli Lilly, eNeura, Equinox, ExpertConnect, GLG, GSK, Guidepoint Global, Healthcare Consultancy Group, Health Science Communications, Impel, Lundbeck, M3 Global Research, Magellan Rx Management, Marcia Berenson Connected Research and Consulting, Medicxi, Navigant Consulting, Neurolief, Nordic BioTech, Novartis, Pulmatrix, Reckner Healthcare, Relevale, Revance, SAI MedPartners, Satsuma, Scion Neurostim, Slingshot Insights, Sorrento, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano; advisory boards: Acorda, Aeon, Alder, Allergan, Amgen, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Biohaven, Charleston Laboratories, Currax, Eli Lilly, GSK, Impel, Lundbeck, Novartis, Satsuma, Theranica, Teva, XOC, Zosano; stock options from Nocira, Percept; salary from American Headache Society and Dartmouth-Hitchcock Medical Center; CME honoraria: American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute Peerview, Medical Education Speakers Network, Miller Medical Communications, North American Center for CME, Physicians’ Education Resource, Rockpointe, ScientiaCME, WebMD/Medscape.

MA reports personal fees from Alder, Allergan, Amgen, Eli Lilly, Novartis and Teva, has no ownership interest and does not own stocks of any pharmaceutical company. MA serves as associate editor of Cephalalgia, associate editor of The Journal of Headache and Pain, and associate editor of Headache, and is the current president of the International Headache Society.

UR has acted as a consultant for Allergan, Amgen, Eli Lilly, Novartis, Teva, has served on advisory boards for Allergan, Amgen, Autonomic Technologies, Eli Lilly, Medscape, Novartis, Teva, and is a member of speakers’ bureaus for Allergan, Amgen, Eli Lilly, Medscape, Novartis, StreamedUp, Teva, and has received research support from the German Federal Ministry of Education and Research (BMBF) and Novartis. YH has served on advisory boards for Amgen, Novartis and Teva.

GB has received unrestricted grants, honoraria, personal fees, and travel grants from Allergan, Amgen, AstraZeneca, European Headache Foundation (EHF), Fresenius, Grünenthal, Janssen Cilag, Lilly, Linde AG, Menarini, Novartis, Österreichische Akademie der Wissenschaften (ÖAW), Österreichische Gesellschaft für Neurologie (ÖGN), Österreichische Kopfschmerzgesellschaft (ÖKSG), Pfizer, Reckitt Benkiser, St. Jude Medical, and Teva.

JHB has nothing to disclose.

HP is an employee of and stockholder in Amgen.

SC is an employee of and stockholder in Amgen.

DEC is an employee of and stockholder in Amgen.

FZ is an employee of and stockholder in Amgen.

JK is an employee of and stockholder in Novartis.

DDM is an employee of and stockholder in Amgen.

© 2021. The Author(s).

Figures

Fig. 1

Change from pre-DBTP in monthly days of any acute headache medication, MSM, or non-MSM use. The change from pre-DBTP in monthly days of any acute headache medication, MSM, or non-MSM use at (A) mean over Months 4, 5, and 6 (EM) and (B) Month 3 (CM) is shown. Baseline values are mean ± SD; change from baseline values are adjusted analysis utilizing a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors and baseline value as covariates and assuming a first-order autoregressive covariance structure. DBTP, double-blind treatment phase; MSM, migraine-specific medication; non-MSM, non-migraine-specific medication, NS, non-significant; SD, standard deviation

Fig. 2

Change in monthly MSMD over DBTP and ATP of the EM study in users of MSM at baseline. Baseline values are not adjusted analysis; DBTP results are presented as adjusted means and 95 % CIs utilizing a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors region and prior/current treatment with migraine prophylactic medication, and baseline value as covariates and assuming a first-order autoregressive covariance structure. P-values for pairwise comparisons are nominal p-values without multiplicity adjustment. ATP results are presented as mean ± SE. ‘All erenumab 70 mg’ in the ATP at Week 52 comprised patients with the following DBTP treatment assignments: placebo (n = 83), erenumab 70 mg (n = 73), erenumab 140 mg (n = 88). ‘All erenumab 140 mg’ in the ATP comprised patients with the following DBTP treatment assignments: placebo (n = 77), erenumab 70 mg (n = 77), erenumab 140 mg (n = 73). ATP, active treatment phase, CI, confidence interval; DBTP, double-blind treatment phase; EM, episodic migraine; M, Month; MSM, migraine-specific medication; MSMD, migraine-specific medication days; SE, standard error

Fig. 3

Change in monthly MSMD over DBTP and OLTP of the CM study in users of MSM at baseline. DBTP results are presented as adjusted means and 95 % CIs utilizing a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors region and medication overuse status, and baseline value as covariates and assuming a first-order autoregressive covariance structure. P-values for pairwise comparisons are nominal p-values without multiplicity adjustment. OLTP results are presented as mean ± SE. For patients switching from 70 mg to 140 mg between Weeks 4 and 28 of the OLTP, by Week 40 patients would have been on 140 mg for at least 12 weeks and would have therefore achieved steady state. Consequently, by Week 52, patients would have been on 140 mg for at least 24 weeks. DBTP, double-blind treatment phase; CI, confidence interval; CM, chronic migraine; M, month; MSM, migraine-specific medication; MSMD, migraine-specific medication days; OLTP, open-label treatment phase; SE, standard error

Fig. 4

Proportion of patients achieving ≥ 50, ≥75 and 100 % reduction from baseline in monthly MSMD in EM study through (A) DBTP and (B) ATP. The common odds ratios and p-values are obtained from a CMH test, stratified by stratification factors region and prior/current treatment with migraine prophylactic medication. P-values for pairwise comparisons are nominal p-values obtained from the CMH test using data including placebo and corresponding erenumab dose group only. ATP, active treatment phase; CMH, Cochran-Mantel-Haenszel, EM, episodic migraine; MSMD, migraine-specific medication days; OR, odds ratio

Fig. 5

Proportion of patients achieving ≥ 50, ≥75 and 100 % reduction from baseline in monthly MSMD in CM study through (A) DBTP and (B) OLTP. The common odds ratios and p-values are obtained from a CMH test, stratified by stratification factors region and medication overuse status. P-values for pairwise comparisons are nominal p-values obtained from the CMH test using data including placebo and corresponding erenumab dose group only. CM, chronic migraine; CMH, Cochran-Mantel-Haenszel, MSMD, migraine-specific medication days; OLTP, open-label treatment phase; OR, odds ratio