Efficacy and safety of erenumab in Japanese migraine patients with prior preventive treatment failure or concomitant preventive treatment: subgroup analyses of a phase 3, randomized trial

Koichi Hirata, Fumihiko Sakai, Takao Takeshima, Noboru Imai, Yasuhiko Matsumori, Ryuji Yoshida, Yotaro Numachi, Cheng Peng, Daniel D Mikol, Sunfa Cheng, Koichi Hirata, Fumihiko Sakai, Takao Takeshima, Noboru Imai, Yasuhiko Matsumori, Ryuji Yoshida, Yotaro Numachi, Cheng Peng, Daniel D Mikol, Sunfa Cheng

Abstract

Background: These subgroup analyses of a Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of erenumab 70 mg in Japanese migraine patients with/without prior preventive treatment failure(s) ("failed-yes" and "failed-no" subgroups) and with/without concomitant preventive treatment ("concomitant preventive-yes" and "concomitant preventive-no" subgroups).

Methods: Overall, 261 patients were randomized; 130 and 131 patients to erenumab 70 mg and placebo, respectively. Subgroup analyses evaluated the change from baseline to Months 4-6 in mean monthly migraine days (MMD) (primary endpoint), achievement of a ≥50% reduction in mean MMD, and change from baseline in mean monthly acute migraine-specific medication (MSM) treatment days. Treatment-emergent adverse events were also evaluated.

Results: Of the 261 patients randomized, 117 (44.8%) and 92 (35.3%) patients were in the failed-yes and concomitant preventive-yes subgroups, respectively. Erenumab 70 mg demonstrated consistent efficacy across all subgroups, with greater reductions from baseline in mean MMD versus placebo at Months 4-6 (treatment difference versus placebo [95% CI], failed-yes: - 1.9 [- 3.3, - 0.4]; failed-no: - 1.4 [- 2.6, - 0.3]; concomitant preventive-yes: - 1.7 [- 3.3, 0.0]; concomitant preventive-no: - 1.6 [- 2.6, - 0.5]). Similar results were seen for achievement of ≥50% reduction in mean MMD and change from baseline in mean monthly acute MSM treatment days. The safety profile of erenumab 70 mg was similar across subgroups, and similar to placebo in each subgroup.

Conclusion: Erenumab was associated with clinically relevant improvements in all efficacy endpoints and was well tolerated across all subgroups of Japanese migraine patients with/without prior preventive treatment failure(s) and with/without concomitant preventive treatment.

Trial registration: Clinicaltrials.gov . NCT03812224. Registered January 23, 2019.

Keywords: Concomitant preventive treatment; Erenumab; Migraine; Prior preventive treatment failure.

Conflict of interest statement

KH: grants from the Ministry of Health, Labor and Welfare, grants from The Japan Agency for Medical Research and Development, and nonfinancial support from Alexion Pharmaceuticals, Inc. FS: membership of advisory boards for Amgen, Eli Lilly and Company, and Teva Pharmaceuticals. SC, CP, RY, YN, DDM: employees and stockholders of Amgen. NI, TT, YM: these authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
LSM change from baseline in mean MMD in (A) failed-yes/no and (B) concomitant preventive-yes/no subgroups. CI confidence interval, LSM least squares mean, MMD monthly migraine days
Fig. 2
Fig. 2
≥50% reduction in mean MMD from baseline in (A) failed-yes/no and (B) concomitant preventive-yes/no subgroups. CI confidence interval, MMD monthly migraine days, OR odds ratio
Fig. 3
Fig. 3
LSM change from baseline in mean monthly acute MSM treatment days in (A) failed-yes/no and (B) concomitant preventive-yes/no subgroups. CI confidence interval, LSM least squares mean, MSM migraine-specific medication

References

    1. Lipton RB, Hamelsky SW, Kolodner KB, Steiner TJ, Stewart WF (2001) Migraine, quality of life, and depression: a population-based case-control study. Neurology 55:629–635
    1. Blumenfeld AM, Varon SF, Wilcox TK, Buse DC, Kawata AK, Manack A, Goadsby PJ, Lipton RB (2011) Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the international burden of migraine study (IBMS). Cephalalgia 31(3):301–315. 10.1177/0333102410381145
    1. Headache Classification Committee of the International Headache Society (IHS) (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38:1–211
    1. Sakai F, Igarashi H. Prevalence of migraine in Japan: a nationwide survey. Cephalalgia. 1997;17(1):15–22. doi: 10.1046/j.1468-2982.1997.1701015.x.
    1. Watanabe Y, Takashima R, Iwanami H, Suzuki S, Igarashi H, Hirata K. Management of chronic migraine in Japan. Rinsho Shinkeigaku. 2013;23(11):1228–1230. doi: 10.5692/clinicalneurol.53.1228.
    1. Araki N, Takeshima T, Ando N, Iizuka T, Igarashi H, Ikeda Y, Ito Y, Inagaki M, Imamura K, Ohkuma H, Ogawa K, Kato Y, Kikui S, Kitamura T, Kudo M, Kuwabara K, Gono Y, Kowa H, Saigoh K, Sato S, Shibata K, Shibata M, Shimazu T, Shimizu T, Suzuki M, Takahashi Y, Takekawa H, Doi H, Nagata E, Nakano T, Hashizume M, Hashimoto S, Hamada J, Hirata K, Fujiki N, Fujita M, Yamane K, Wajima K, Watanabe Y. Clinical practice guideline for chronic headache 2013. Neurol Clin Neurosci. 2019;7(5):231–259. doi: 10.1111/ncn3.12322.
    1. Ueda K, Ye W, Lombard L, Kuga A, Kim Y, Cotton S, Jackson J, Treuer T. Real-world treatment patterns and patient-reported outcomes in episodic and chronic migraine in Japan: analysis of data from the Adelphi migraine disease specific programme. J Headache Pain. 2019;20(1):68. doi: 10.1186/s10194-019-1012-1.
    1. Meyers JL, Davis KL, Lenz RA, Sakai F, Xue F. Treatment patterns and characteristics of patients with migraine in Japan: a retrospective analysis of health insurance claims data. Cephalalgia. 2019;39(12):1518–1534. doi: 10.1177/0333102419851855.
    1. Hirata K, Ueda K, Ye W, Kim Y, Komori M, Jackson J, Cotton S, Rajan N, Treuer T (2020) Factors associated with insufficient response to acute treatment of migraine in Japan: analysis of real-world data from the Adelphi migraine disease specific Programme. BMC Neurol 20(1):274. 10.1186/s12883-020-01848-4
    1. Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425–434. doi: 10.1016/S1474-4422(17)30083-2.
    1. Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123–2132. doi: 10.1056/NEJMoa1705848.
    1. Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38(6):1026–1037. doi: 10.1177/0333102418759786.
    1. Inc A. Aimovig™ prescribing information. 2018.
    1. Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Lenz R, Wang Y, Cheng S, Hirama T, Mikol DD. A randomized phase 2 study of erenumab for the prevention of episodic migraine in Japanese adults. Headache. 2019;59(10):1731–1742. doi: 10.1111/head.13652.
    1. Goadsby PJ, Paemeleire K, Broessner G, Brandes J, Klatt J, Zhang F, Picard H, Lenz R, Mikol DD. 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. 2019;39(7):817–826. doi: 10.1177/0333102419835459.
    1. Ashina M, Tepper S, Brandes JL, Reuter U, Boudreau G, Dolezil D, Cheng S, Zhang F, Lenz R, Klatt J, Mikol DD. 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. Cephalalgia. 2018;38(10):1611–1621. doi: 10.1177/0333102418788347.
    1. Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD, Klatt J. 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. 2018;392(10161):2280–2287. doi: 10.1016/S0140-6736(18)32534-0.
    1. Takeshima T, Sakai F, Hirata K, Imai N, Matsumori Y, Yoshida R, Peng C, Cheng S, Mikol DD. Erenumab treatment for migraine prevention in Japanese patients: efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. Headache. 2021;61(6):927–935. doi: 10.1111/head.14138.
    1. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, Quality standards Subcommittee of the American Academy of neurology and the American headache society (2012) 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 [published correction appears in Neurology. 2013;80:871]. Neurology 78(17):1337–1345. 10.1212/WNL.0b013e3182535d20
    1. Eadie MJ. Clinically significant drug interactions with agents specific for migraine attacks. CNS Drugs. 2001;15(2):105–118. doi: 10.2165/00023210-200115020-00003.
    1. Seng EK, Rains JA, Nicholson RA, Lipton RB. Improving medication adherence in migraine treatment. Curr Pain Headache Rep. 2015;19(6):24. doi: 10.1007/s11916-015-0498-8.
    1. Berger A, Bloudek LM, Varon SF, Oster G. Adherence with migraine prophylaxis in clinical practice. Pain Pract. 2012;12(7):541–549. doi: 10.1111/j.1533-2500.2012.00530.x.
    1. Blumenfeld AM, Bloudek LM, Becker WJ, Buse DC, Varon SF, Maglinte GA, Wilcox TK, Kawata AK, Lipton RB (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. 10.1111/head.12055
    1. Tepper SJ, Diener H-C, Ashina M, Brandes JL, Friedman DI, Reuter U, Cheng S, Nilsen J, Leonardi DK, Lenz RA, Mikol DD. Erenumab in chronic migraine with medication overuse: subgroup analysis of a randomized trial. Neurology. 2019;92(20):e2309–e2320. doi: 10.1212/WNL.0000000000007497.

Source: PubMed

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