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Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache: Final Results From a Phase 4 Randomized Placebo-Controlled Study

. 2025 Aug ; 32 (8) : e70328.

Language English Country Great Britain, England Media print

Document type Journal Article, Randomized Controlled Trial, Clinical Trial, Phase IV, Multicenter Study

Grant support
Amgen Inc.

BACKGROUND: Erenumab-induced medication overuse headache (MOH) remission in participants with chronic migraine (CM) in a prospective, Phase 4, randomized, placebo-controlled trial with an open-label treatment period (OLTP). We present 1-year results from the combined double-blind treatment period (DBTP) and OLTP for the stratified nonopioid cohort. METHODS: Participants with CM-MOH were randomized 1:1:1 to subcutaneous 70 or 140 mg erenumab every 4 weeks (QM) or placebo for the initial 24 weeks (DBTP). Those successfully completing DBTP could continue the 28-week OLTP, maintaining the same erenumab dose received during DBTP or, if receiving placebo, randomly assigned 1:1 to erenumab 70 or 140 mg QM. OLTP endpoints were exploratory. RESULTS: Overall, 552 participants received erenumab (70 mg, n = 274; 140 mg, n = 278); 95.3% completed OLTP. One-year MOH relapse in participants who achieved MOH remission at DBTP Month 6 was 2.7% (3/111) and 2.4% (3/124) with erenumab 70 and 140 mg, respectively; absence of MOH at study end was observed in 69.0% (189/274) and 75.5% (210/278) of participants. Sustained MOH absence over 1 year was reported in 60.5% (107/177) and 68.8% (119/173) of participants, respectively. Sustained improvements in measures of headache days, medication days, and function were observed in both groups. No new safety concerns were identified (grade ≥ 3, 35 [6.3%]; serious, 17 [3.1%]; adverse events leading to treatment discontinuation, 5 [0.9%]). CONCLUSIONS: Erenumab was effective in inducing and sustaining MOH remission and improving function over 1 year. Treatment compliance remained high, with safety events consistent with erenumab's known safety profile. TRIAL REGISTRATION: NCT03971071.

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Headache Classification Committee of the International Headache Society (IHS) , “The International Classification of Headache Disorders, 3rd Edition,” Cephalalgia 38, no. 1 (2018): 1–211. PubMed

Fischer M. A. and Jan A., Medication‐Overuse Headache (StatPearls, 2024). PubMed

Lipton R. B., Nicholson R. A., Reed M. L., et al., “Diagnosis, Consultation, Treatment, and Impact of Migraine in the US: Results of the OVERCOME (US) Study,” Headache 62, no. 2 (2022): 122–140. PubMed PMC

Katsarava Z., Muessig M., Dzagnidze A., Fritsche G., Diener H. C., and Limmroth V., “Medication Overuse Headache: Rates and Predictors for Relapse in a 4‐Year Prospective Study,” Cephalalgia 25, no. 1 (2005): 12–15. PubMed

Liu H., Zhang M., Chen X., Sun S., Dong Z., and Yu S., “Rates and Predictors of Relapse in Medication Overuse Headache: A Clinic‐Based Study From China,” European Neurology 82, no. 4–6 (2019): 68–74. PubMed

Parikh S. K., Kempner J., and Young W. B., “Stigma and Migraine: Developing Effective Interventions,” Current Pain and Headache Reports 25, no. 11 (2021): 75. PubMed PMC

Scaratti C., Covelli V., Guastafierro E., et al., “A Qualitative Study on Patients With Chronic Migraine With Medication Overuse Headache: Comparing Frequent and Non‐Frequent Relapsers,” Headache 58, no. 9 (2018): 1373–1388. PubMed

Giri S., Tronvik E., Linde M., Pedersen S. A., and Hagen K., “Randomized Controlled Studies Evaluating Topiramate, Botulinum Toxin Type A, and mABs Targeting CGRP in Patients With Chronic Migraine and Medication Overuse Headache: A Systematic Review and Meta‐Analysis,” Cephalalgia 43, no. 4 (2023): 3331024231156922. PubMed

Marmura M. J., Diener H. C., Cowan R. P., et al., “Preventive Migraine Treatment With Eptinezumab Reduced Acute Headache Medication and Headache Frequency to Below Diagnostic Thresholds in Patients With Chronic Migraine and Medication‐Overuse Headache,” Headache 61, no. 9 (2021): 1421–1431. PubMed PMC

Dodick D. W., Doty E. G., Aurora S. K., et al., “Medication Overuse in a Subgroup Analysis of Phase 3 Placebo‐Controlled Studies of Galcanezumab in the Prevention of Episodic and Chronic Migraine,” Cephalalgia 41, no. 3 (2021): 340–352. PubMed

Tepper S. J., Diener H. C., Ashina M., et al., “Erenumab in Chronic Migraine With Medication Overuse: Subgroup Analysis of a Randomized Trial,” Neurology 92, no. 20 (2019): e2309–e2320. PubMed PMC

Tepper S. J., Dodick D. W., Lanteri‐Minet M., et al., “Efficacy and Safety of Erenumab for Nonopioid Medication Overuse Headache in Chronic Migraine: A Phase 4, Randomized, Placebo‐Controlled Trial,” JAMA Neurology 81, no. 11 (2024): 1140–1149. PubMed PMC

Tepper S. J., Lipton R. B., Silberstein S. D., et al., “Long‐Term Efficacy and Safety of Erenumab in Patients With Chronic Migraine and Acute Medication Overuse: A Subgroup Analysis,” Headache 63, no. 6 (2023): 730–742. PubMed

Hirata K., Takeshima T., Sakai F., et al., “Long‐Term Efficacy and Safety of Erenumab in Japanese Patients With Episodic and Chronic Migraine: Results From a 28‐Week Open‐Label Treatment Period of a Randomised Trial,” BMJ Open 13, no. 8 (2023): e068616. PubMed PMC

Bendtsen L., Munksgaard S., Tassorelli C., et al., “Disability, Anxiety and Depression Associated With Medication‐Overuse Headache Can Be Considerably Reduced by Detoxification and Prophylactic Treatment. Results From a Multicentre, Multinational Study (COMOESTAS Project),” Cephalalgia 34, no. 6 (2014): 426–433. PubMed

Tassorelli C., Jensen R., Allena M., et al., “A Consensus Protocol for the Management of Medication‐Overuse Headache: Evaluation in a Multicentric, Multinational Study,” Cephalalgia 34, no. 9 (2014): 645–655. PubMed

Chiang C.‐C., Schwedt T. J., Wang S.‐J., and Dodick D. W., “Treatment of Medication‐Overuse Headache: A Systematic Review,” Cephalalgia 36, no. 4 (2015): 371–386. PubMed

Carlsen L. N., Munksgaard S. B., Nielsen M., et al., “Comparison of 3 Treatment Strategies for Medication Overuse Headache: A Randomized Clinical Trial,” JAMA Neurology 77, no. 9 (2020): 1069–1078. PubMed PMC

Ashina M., Goadsby P. J., Reuter U., et al., “Long‐Term Efficacy and Safety of Erenumab in Migraine Prevention: Results From a 5‐Year, Open‐Label Treatment Phase of a Randomized Clinical Trial,” European Journal of Neurology 28, no. 5 (2021): 1716–1725. PubMed PMC

Tepper S. J., Ashina M., Reuter U., et al., “Long‐Term Safety and Efficacy of Erenumab in Patients With Chronic Migraine: Results From a 52‐Week, Open‐Label Extension Study,” Cephalalgia 40, no. 6 (2020): 543–553. PubMed

Kudrow D., Cady R. K., Allan B., et al., “Long‐Term Safety and Tolerability of Eptinezumab in Patients With Chronic Migraine: A 2‐Year, Open‐Label, Phase 3 Trial,” BMC Neurology 21, no. 1 (2021): 126. PubMed PMC

Sakai F., Suzuki N., Ning X., et al., “Long‐Term Safety and Tolerability of Fremanezumab for Migraine Preventive Treatment in Japanese Outpatients: A Multicenter, Randomized, Open‐Label Study,” Drug Safety 44, no. 12 (2021): 1355–1364. PubMed PMC

Pozo‐Rosich P., Detke H. C., Wang S., et al., “Long‐Term Treatment With Galcanezumab in Patients With Chronic Migraine: Results From the Open‐Label Extension of the REGAIN Study,” Current Medical Research and Opinion 38, no. 5 (2022): 731–742. PubMed

Krymchantowski A., Jevoux C., Krymchantowski A. G., and Silva‐Neto R. P., “Medication Overuse Headache, Chronic Migraine and Monoclonal Antibodies Anti‐CGRP: A Real‐World Study,” Clinical Neuropharmacology 46, no. 5 (2023): 181–185. PubMed

Yu S., Zhou J., Luo G., et al., “Efficacy and Safety of Eptinezumab in Patients With Chronic Migraine and Medication‐Overuse Headache: A Randomized, Double‐Blind, Placebo‐Controlled Study,” BMC Neurology 23, no. 1 (2023): 441. PubMed PMC

Blumenfeld A., Kudrow D., McAllister P., Boserup L. P., Hirman J., and Cady R., “Long‐Term Effectiveness of Eptinezumab in the Treatment of Patients With Chronic Migraine and Medication‐Overuse Headache,” Headache 64, no. 7 (2024): 738–749. PubMed

Bongsebandhu‐phubhakdi S. and Srikiatkhachorn A., “Pathophysiology of Medication‐Overuse Headache: Implications From Animal Studies,” Current Pain and Headache Reports 16, no. 1 (2012): 110–115. PubMed

Johnson B. and Freitag F. G., “New Approaches to Shifting the Migraine Treatment Paradigm,” Frontiers in Pain Research 3 (2022): 873179. PubMed PMC

Kopruszinski C. M., Xie J. Y., Eyde N. M., et al., “Prevention of Stress‐ or Nitric Oxide Donor‐Induced Medication Overuse Headache by a Calcitonin Gene‐Related Peptide Antibody in Rodents,” Cephalalgia 37, no. 6 (2017): 560–570. PubMed

Schwedt T. J., Hentz J. G., Sahai‐Srivastava S., et al., “Patient‐Centered Treatment of Chronic Migraine With Medication Overuse: A Prospective, Randomized, Pragmatic Clinical Trial,” Neurology 98, no. 14 (2022): e1409–e1421. PubMed

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NCT03971071

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