Long-Term Safety and Tolerability of Fremanezumab for Migraine Preventive Treatment in Japanese Outpatients: A Multicenter, Randomized, Open-Label Study

Fumihiko Sakai, Norihiro Suzuki, Xiaoping Ning, Miki Ishida, Chiharu Usuki, Katsuhiro Iba, Yuki Isogai, Nobuyuki Koga, Fumihiko Sakai, Norihiro Suzuki, Xiaoping Ning, Miki Ishida, Chiharu Usuki, Katsuhiro Iba, Yuki Isogai, Nobuyuki Koga

Abstract

Introduction: Early discontinuation and poor adherence are common limitations of conventional preventive migraine medications that limit their long-term efficacy. Therefore, a migraine preventive medication with favorable long-term safety is warranted.

Objective: This study aimed to evaluate the long-term safety and tolerability of fremanezumab for the preventive treatment of chronic or episodic migraine in Japanese patients.

Methods: In this 52-week, randomized, open-label, parallel-group study, fremanezumab monthly or quarterly was administered in newly enrolled Japanese patients with chronic migraine or episodic migraine. Safety was assessed by monitoring of treatment-emergent adverse events, including injection-site reactions, laboratory and vital sign assessments. Newly enrolled patients and rollover patients from previous phase IIb/III trials who did not receive fremanezumab in this study were included in the immunogenicity testing cohort (n = 587). Efficacy outcomes included changes from baseline in the average monthly migraine days and headache days of at least moderate severity. Other efficacy outcomes included changes in disability scores.

Results: A total of 50 patients were enrolled with chronic migraine (monthly, n = 17; quarterly, n = 17) or episodic migraine (monthly, n = 8; quarterly, n = 8). The most commonly reported treatment-emergent adverse events were nasopharyngitis (64.0%) and injection-site reactions (erythema, 24.0%; induration, 10.0%; pain, 8.0%; pruritus, 6.0%). The discontinuation rate was low (4.0% from adverse events, 2.0% from a lack of efficacy) and no deaths were reported. The incidence of anti-drug antibody development was low (2.4%). Fremanezumab reduced monthly migraine days and headache days of at least moderate severity from 1 month after initial administration, and this effect was maintained with no worsening throughout 12 months. Fremanezumab also led to sustained reductions in any acute headache medication use and headache-related disability at 12 months.

Conclusions: Fremanezumab administered monthly and quarterly was well tolerated in patients with chronic migraine and episodic migraine and led to sustained improvements in monthly migraine days and headache days of at least moderate severity throughout 12 months.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT03303105.

Conflict of interest statement

FS reports being an advisor for Otsuka Pharmaceutical Co. Ltd., Eli Lilly, and Amgen. NS reports personal fees from Otsuka Pharmaceutical Co., Ltd. XN is a full-time employee of Teva Branded Pharmaceutical Products R&D. MI, CU, KI, YI, and NK are full-time employees of Otsuka Pharmaceutical Co., Ltd.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study design (newly enrolled patients). CM chronic migraine, EM episodic migraine, EOT end of treatment, IMP investigational medicinal product, V visit
Fig. 2
Fig. 2
Patient disposition

References

    1. Blumenfeld AM, Bloudek LM, Becker WJ, Buse DC, Varon SF, Maglinte GA, et al. 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. 2013;53(4):644–655. doi: 10.1111/head.12055.
    1. Loder EW, Rizzoli P. Tolerance and loss of beneficial effect during migraine prophylaxis: clinical considerations. Headache. 2011;51(8):1336–1345. doi: 10.1111/j.1526-4610.2011.01986.x.
    1. Ueda K, Ye W, Lombard L, Kuga A, Kim Y, Cotton S, et al. 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. Bonafede M, Wilson K, Xue F. Long-term treatment patterns of prophylactic and acute migraine medications and incidence of opioid-related adverse events in patients with migraine. Cephalalgia. 2019;39(9):1086–1098. doi: 10.1177/0333102419835465.
    1. Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35(6):478–488. doi: 10.1177/0333102414547138.
    1. Woolley JM, Bonafede MM, Maiese BA, Lenz RA. Migraine prophylaxis and acute treatment patterns among commercially insured patients in the United States. Headache. 2017;57(9):1399–1408. doi: 10.1111/head.13157.
    1. Hepp Z, Bloudek LM, Varon SF. Systematic review of migraine prophylaxis adherence and persistence. J Manag Care Pharm. 2014;20(1):22–33. doi: 10.18553/jmcp.2014.20.1.22.
    1. Hepp Z, Dodick DW, Varon SF, Chia J, Matthew N, Gillard P, et al. Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: a retrospective claims analysis. Cephalalgia. 2017;37(5):470–485. doi: 10.1177/0333102416678382.
    1. Edvinsson L. Role of CGRP in migraine. In: Brain SD, Geppetti P, editors. Calcitonin gene-related peptide (CGRP) mechanisms. Handbook of experimental pharmacology. Cham: Springer International Publishing; 2019. pp. 121–130.
    1. Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies—successful translation from bench to clinic. Nat Rev Neurol. 2018;14(6):338–350. doi: 10.1038/s41582-018-0003-1.
    1. American Headache Society The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1–18.
    1. Dodick DW. CGRP ligand and receptor monoclonal antibodies for migraine prevention: evidence review and clinical implications. Cephalalgia. 2019;39(3):445–458. doi: 10.1177/0333102418821662.
    1. Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA. 2018;319(19):1999–2008. doi: 10.1001/jama.2018.4853.
    1. Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113–2122. doi: 10.1056/NEJMoa1709038.
    1. Goadsby PJ, Silberstein SD, Yeung PP, Cohen JM, Ning X, Yang R, et al. Long-term safety, tolerability, and efficacy of fremanezumab in migraine: a randomized study. Neurology. 2020;95:e2487–e2499. doi: 10.1212/WNL.0000000000010600.
    1. Sakai F, Suzuki N, Kim B-K, Igarashi H, Hirata K, Takeshima T, et al. Efficacy and safety of fremanezumab for chronic migraine prevention: multicenter, randomized, double-blind, placebo controlled, parallel-group trial in Japanese and Korean patients. Headache. 2021;61:1092–1101. doi: 10.1111/head.14169.
    1. Sakai F, Suzuki N, Kim BK, Tatsuoka Y, Imai N, Ning X, et al. Efficacy and safety of fremanezumab for episodic migraine prevention: multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in Japanese and Korean patients. Headache. 2021;61:1102–1111. doi: 10.1111/head.14178.
    1. Mundt JC, Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Modell JG. Feasibility and validation of a computer-automated Columbia-Suicide Severity Rating Scale using interactive voice response technology. J Psychiatr Res. 2010;44(16):1224–1228. doi: 10.1016/j.jpsychires.2010.04.025.
    1. Kosinski M, Bayliss MS, Bjorner JB, Ware JE, Jr, Garber WH, Batenhorst A, et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12(8):963–974. doi: 10.1023/A:1026119331193.
    1. Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology. 2001;56(6 Suppl. 1):S20–S28. doi: 10.1212/WNL.56.suppl_1.S20.
    1. Committee for Proprietary Medicinal Products. ICH topic E 1: population exposure: the extent of population exposure to assess clinical safety. CPMP/ICH/375/95. Available from: . Accessed 18 Dec 2020.
    1. Ning X, Cohen JM, Wu M, Nagaoka T, Sakai F. Efficacy and safety of fremanezumab versus placebo for the preventive treatment of episodic migraine (EM) and chronic migraine (CM) in a subpopulation of Japanese patients: results from the randomized, double-blind, phase 3 HALO studies. Presented at the 48th Annual Meeting of the Japanese Headache Society; 7–8 November 2020.

Source: PubMed

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