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The Journal of Headache and Pain

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Open Access 01-12-2022 | Migraine | Research

Erenumab versus topiramate: post hoc efficacy analysis from the HER-MES study

Authors: Marc Ehrlich, Christian Hentschke, Christian Sieder, Monika Maier-Peuschel, Uwe Reuter

Published in: The Journal of Headache and Pain | Issue 1/2022

Abstract

Objective

HER-MES was the first head-to-head, phase 4 trial to assess the tolerability and effectiveness of erenumab against standard of care treatment (topiramate). This post hoc analysis compared the efficacy of erenumab with topiramate in patients who completed the trial on study medication.

Methods

Post hoc sensitivity analysis was performed using the full analysis set. Outcomes assessed included the proportion of patients with a ≥50% reduction in monthly migraine days (MMD) from baseline (50% responder rate), over the last 3 months (months 4, 5, and 6) of the double-blind treatment phase (DBTP), the 50% responder rate during the first month of the DBTP, and change from baseline in MMD during the DBTP. Multiple imputation was done for efficacy values of patients who discontinued study treatment.

Results

Patients (N = 777) were randomly assigned (1:1) to either 70 or 140 mg/month erenumab (N = 389) or 50–100 mg/day topiramate (N = 388). Of these, 334 patients (85.9%) receiving erenumab, and 231 patients (59.5%) receiving topiramate completed the DBTP on study medication. Patients on study medication until the end of the DBTP received a mean dose of 119 mg/month for erenumab and 92 mg/day for topiramate. At month 1, a significantly greater proportion of patients receiving erenumab (39.2%) reported ≥50% reduction in MMD from baseline compared with those receiving topiramate (24.0%; p < 0.001). In the last 3 months, a significantly larger proportion of patients receiving erenumab (60.3%) achieved ≥50% reduction in MMD from baseline compared with those receiving topiramate (43.3%; p < 0.001). Patients receiving erenumab demonstrated significantly greater reductions in MMD during the last 3 months from baseline versus those receiving topiramate (− 6.13 vs − 4.90; 95% CI: − 1.87 to − 0.61; p < 0.001).

Conclusions

This post hoc analysis demonstrated significantly superior efficacy of erenumab versus topiramate in achieving a ≥50% reduction in MMD with an early onset of efficacy.

Trial registration

ClinicalTrials.gov NCT03828539.

Vos T, Abajobir AA, Annafati C, Abbas KM, Abate KH et al (2017) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet 390(10100):1211–1259. https://doi.org/10.1016/S0140-6736(17)32154-2CrossRef

Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z (2020) Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain 21(1):137. https://doi.org/10.1186/s10194-020-01208-0CrossRefPubMedPubMedCentral

Buse DC, Rupnow MF, Lipton RB (2009) Assessing and managing all aspects of migraine: migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life. Mayo Clin Proc 84(5):422–435. https://doi.org/10.1016/S0025-6196(11)60561-2CrossRefPubMedPubMedCentral

Holmes WF, MacGregor EA, Sawyer JP, Lipton RB (2001) Information about migraine disability influences physicians’ perceptions of illness severity and treatment needs. Headache 41(4):343–350. https://doi.org/10.1046/j.1526-4610.2001.111006343.xCrossRefPubMed

Lipton RB, Hahn SR, Cady RK, Brandes JL, Simons SE, Bain PA et al (2008) In-office discussions of migraine: results from the American Migraine Communication Study. J Gen Intern Med 23(8):1145–1151. https://doi.org/10.1007/s11606-008-0591-3CrossRefPubMedPubMedCentral

Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E et al (2017) Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 78(17):1337–1345. https://doi.org/10.1212/WNL.0b013e3182535d20CrossRef

Shapiro RE (2012) Preventive treatment of migraine. Headache 52(Suppl 2):65–69. https://doi.org/10.1111/j.1526-4610.2012.02242.xCrossRefPubMed

Hepp Z, Dodick DW, Varon SF, Chia J, Matthew N, Gillard P et al (2017) Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: a retrospective claims analysis. Cephalagia 37(5):470–485. https://doi.org/10.1177/0333102416678382CrossRef

Blumenfeld AM, Bloudek LM, Becker WJ, Buse DC, Varon SF, Maglinte GA et al (2013) Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMS-II). Headache 53(4):644–655. https://doi.org/10.1111/head.12055CrossRefPubMed

10.

Yaldo AZ, Wertz DA, Rupnow MF, Quimbo RM (2008) Persistence with migraine prophylactic treatment and acute migraine medication utilization in the managed care setting. Clin Ther 30(12):2452–2460. https://doi.org/10.1016/j.clinthera.2008.12.010CrossRefPubMed

11.

Berger A, Bloudek LM, Varon SF, Oster G (2012) Adherence with migraine prophylaxis in clinical practice. Pain Pract 12(7):541–549. https://doi.org/10.1111/j.1533-2500.2012.00530.xCrossRefPubMed

12.

Dekker F, Neven AK, Andriesse B, Kernick D, Reis R, Ferrari MD et al (2012) Prophylactic treatment of migraine; the patient’s view, a qualitative study. BMC Fam Pract 13:13. https://doi.org/10.1186/1471-2296-13-13CrossRefPubMedPubMedCentral

13.

Dekker F, Neven AK, Andriesse B, Kernick D, Ferrari MD, Assendelft WJ (2012) Prophylactic treatment of migraine by GPs: a qualitative study. Br J Gen Pract 62(597):e268–e274. https://doi.org/10.3399/bjgp12X636100CrossRefPubMedPubMedCentral

14.

The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1–18. https://doi.org/10.1111/head.13456

15.

Steiner TJ, Jensen R, Katsarava Z, Linde M, MacGregor EA, Osipova V et al (2019) Aids to management of headache disorders in primary care (2nd edition): on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache. J Headache Pain 20(1):57. https://doi.org/10.1186/s10194-018-0899-2CrossRefPubMedPubMedCentral

16.

Silberstein SD, Neto W, Schmitt J, Jacobs D, MIGR-001 Study Group (2004) Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol 61(4):490–495. https://doi.org/10.1001/archneur.61.4.490CrossRefPubMed

17.

Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J et al (2004) Topiramate for migraine prevention: a randomized controlled trial. JAMA 291(8):965–973. https://doi.org/10.1001/jama.291.8.965CrossRefPubMed

18.

Diener HC, Tfelt-Hansen P, Dahlof C, Láinez MJ, Sandrini G, Wang SJ et al (2004) Topiramate in migraine prophylaxis–results from a placebo-controlled trial with propranolol as an active control. J Neurol 251(8):943–950. https://doi.org/10.1007/s00415-004-0464-6CrossRefPubMed

19.

Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M et al (2016) Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 15(4):382–390. https://doi.org/10.1016/S1474-4422(16)00019-3CrossRefPubMed

20.

Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F et al (2017) A controlled trial of erenumab for episodic migraine. N Engl J Med 377(22):2123–2132. https://doi.org/10.1056/NEJMoa1705848CrossRefPubMed

21.

Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S et al (2017) Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 16(6):425–434. https://doi.org/10.1016/S1474-4422(17)30083-2CrossRefPubMed

22.

Goadsby PJ, Paemeleire K, Broessner G, Brandes J, Klatt J, Zhang F et al (2019) Efficacy and safety of erenumab (AMG334) in episodic migraine patients with prior preventive treatment failure: a subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia 39(7):817–826. https://doi.org/10.1177/0333102419835459CrossRefPubMed

23.

Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V et al (2018) ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 38(6):1026–1037. https://doi.org/10.1177/0333102418759786CrossRefPubMed

24.

Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD et al (2018) Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet 392(10161):2280–2287. https://doi.org/10.1016/S0140-6736(18)32534-0CrossRefPubMed

25.

Ashina M, Tepper S, Brandes JL, Reuter U, Boudreau G, Dolezil D et al (2018) Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: a subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalgia 38(10):1611–1621. https://doi.org/10.1177/0333102418788347CrossRef

26.

Wang SJ, Roxas AA Jr, Saravia B, Kim BK, Chowdhury D, Riachi N et al (2021) Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: the EMPOwER study. Cephalalgia 41(13):1285–1297. https://doi.org/10.1177/03331024211024160CrossRefPubMedPubMedCentral

27.

Reuter U, Ehrlich M, Gendolla A, Heinze A, Klatt J, Wen S et al (2022) Erenumab versus topiramate for the prevention of migraine - a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia 42(2):108–118. https://doi.org/10.1177/03331024211053571CrossRefPubMed

28.

Headache Classification Committee of the International Headache Society (2018) The international classification of headache disorders, 3rd edition. Cephalalgia 38(1):1–211. https://doi.org/10.1177/0333102417738202CrossRef

29.

Ehrlich M, Maier-Peuschel M, Sieder C, Hentschke C, Reuter U (2021) Erenumab versus topiramate for the prevention of migraine: results of a post hoc efficacy analysis. IHS and EHF joint congress. J Headache Pain 22:103. https://doi.org/10.1186/s10194-021-01293-9CrossRef

30.

Schwedt T, Reuter U, Tepper S, Ashina M, Kudrow D, Broessner G et al (2018) Early onset of efficacy with erenumab in patients with episodic and chronic migraine. J Headache Pain 19(1):92. https://doi.org/10.1186/s10194-018-0923-6CrossRefPubMedPubMedCentral

31.

Hirata K, Takeshima T, Sakai F, Imai N, Matsumori Y, Tatsuoka Y et al (2022) Early onset of efficacy with erenumab for migraine prevention in Japanese patients: analysis of two randomized, double-blind, placebo-controlled studies. Brain Behav 12(3):e2526. https://doi.org/10.1002/brb3.2526CrossRefPubMedPubMedCentral

32.

Singal AG, Higgins PD, Waljee AK (2014) A primer on effectiveness and efficacy trials. Clinc Transl Gastroenterol 5(1):e45. https://doi.org/10.1038/ctg.2013.13CrossRef

33.

Kawata AK, Shah N, Poon JL, Shaffer S, Sapra S, Wilcox TK et al (2021) Understanding the migraine treatment landscape prior to the introduction of calcitonin gene-related peptide inhibitors: results from the Assessment of Tolerability and Effectiveness in MigrAINe Patients using Preventive Treatment (ATTAIN) study. Headache 61(3):438–454. https://doi.org/10.1111/head.14053CrossRefPubMedPubMedCentral

34.

Yang CP, Zeng BY, Chang CM, Shih PH, Yang CC, Tseng PT et al Comparative effectiveness and tolerability of the pharmacology of monoclonal antibodies targeting the calcitonin gene-related peptide and its receptor for the prevention of chronic migraine: a network meta-analysis of randomized controlled trials. Neurotherapeutics 18(4):2639–2650. https://doi.org/10.1007/s13311-021-01128-0

35.

Vandervorst F, Van Deun L, Van Dycke A, Paemeleire K, Reuter U, Schoenen J et al (2021) CGRP monoclonal antibodies in migraine: an efficacy and tolerability comparison with standard prophylactic drugs. J Headache Pain 22(1):128. https://doi.org/10.1186/s10194-021-01335-2CrossRefPubMedPubMedCentral

36.

Overeem LH, Raffaelli B, Mecklenburg J, Kelderman T, Neeb L, Reuter U (2021) Indirect comparison of topiramate and monoclonal antibodies against CGRP or its receptor for the prophylaxis of episodic migraine: a systematic review with meta-analysis. CNS Drugs 35(8):805–820. https://doi.org/10.1007/s40263-021-00834-9CrossRefPubMedPubMedCentral

Title: Erenumab versus topiramate: post hoc efficacy analysis from the HER-MES study
Authors: Marc Ehrlich
Christian Hentschke
Christian Sieder
Monika Maier-Peuschel
Uwe Reuter
Publication date: 01-12-2022
Publisher: Springer Milan
Keywords: Migraine
Care
Topiramate
Erenumab
Published in: The Journal of Headache and Pain / Issue 1/2022
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-022-01511-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Erenumab versus topiramate: post hoc efficacy analysis from the HER-MES study

Abstract

Objective

Methods

Results

Conclusions

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Trial registration

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