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. 2023 Apr 20:16:1311-1319.
doi: 10.2147/JPR.S393854. eCollection 2023.

Fremanezumab for Chronic Migraine Prevention in Japanese Patients: Subgroup Analysis from Two International Trials

Kazumasa Saigoh  1 , Takao Takeshima  2 , Masami Nakai  3 , Yoshiyuki Shibasaki  4 , Miki Ishida  5 , Xiaoping Ning  6 , Steve Barash  6 , Yuki Isogai  4 , Nobuyuki Koga  7
Affiliations

Fremanezumab for Chronic Migraine Prevention in Japanese Patients: Subgroup Analysis from Two International Trials

Kazumasa Saigoh et al. J Pain Res. .

Abstract

Purpose: Fremanezumab monoclonal antibody therapy has demonstrated efficacy for chronic migraine (CM) with rapid onset and good tolerability. This subgroup analysis of two clinical trials (Japanese and Korean CM Phase 2b/3 [NCT03303079] and HALO CM Phase 3 [NCT02621931]) aimed to evaluate the efficacy and safety of fremanezumab in Japanese patients.

Patients and methods: Both trials randomly assigned eligible patients at baseline (1:1:1 ratio) to subcutaneous monthly fremanezumab, quarterly fremanezumab, or placebo at 4-week intervals. The primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12-week period after the first dose of study medication (analyzed by ANCOVA over 12 weeks and MMRM over initial 4 weeks). Secondary endpoints examined other aspects of efficacy, including medication use and disability.

Results: A total of 479 and 109 patients were Japanese in the Japanese and Korean CM Phase 2b/3 and HALO CM trials, respectively. Baseline and treatment characteristics were generally similar between treatment groups for both trials. Results of subgroup analyses for the primary endpoint according to ANCOVA demonstrated the superiority of fremanezumab over placebo in Japanese patients (quarterly fremanezumab, p=0.0005; monthly fremanezumab, p=0.0002 in both trials). Results using the MMRM analysis confirmed the rapid onset of action in this population. Results of the secondary endpoints further supported the efficacy of fremanezumab in Japanese patients. Fremanezumab was well tolerated with nasopharyngitis and injection-site reactions representing the most common adverse events in all treatment groups.

Conclusion: Despite the limitations of subgroup analyses, these consistent results confirm the efficacy and tolerability of fremanezumab in Japanese patients with CM.

Keywords: Japanese; calcitonin gene-related peptide; chronic migraine; fremanezumab.

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Conflict of interest statement

KS has received grants from Sumitomo Pharma Co., Ltd.; consulting fees from Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd.; payment for lectures from AMGEN Inc., Daiichi Sankyo Company, Eisai Co., Ltd., Eli Lilly Japan, Otsuka Pharmaceutical Co., Ltd., Sanofi Japan, Sumitomo Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd.; committee member for Japanese Society of Headache, Japanese Society of Human Genetics. TT has received honoraria for lectures from Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Amgen K.K., Eli Lilly and Company, Daiichi Sankyo; research funds under contract from Eisai Co., Ltd., Eli Lilly and Company, Amgen K.K., Allergan Japan K.K., Shionogi & Co., Ltd., Lundbeck Japan K.K. MN, YS, MI, YI, and NK are full-time employees of Otsuka Pharmaceutical Co., Ltd. XN and SB are full-time employees of Teva Branded Pharmaceutical Products. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Primary endpoint according to ANCOVA analysis for Japanese patients enrolled in the (A) Japanese and Korean phase 2b/3 trial, and (B) HALO trial.
Figure 2
Figure 2
Changes from baseline in the average number of headache days of at least moderate severity (MMRM analysis) over (A) 3 months and (B) 4 weeks for Japanese patients enrolled in the Japanese and Korean phase 2b/3 trial. An asterisk denotes p<0.05 and a dagger denotes p<0.0001 for the comparison of fremanezumab monthly or quarterly with placebo; mixed-effects model for repeated measures (MMRM) analysis.
See this image and copyright information in PMC

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References

    1. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629–808. doi:10.1177/0333102413485658 - DOI - PubMed
    1. Natoli JL, Manack A, Dean B, et al. Global prevalence of chronic migraine: a systematic review. Cephalalgia. 2010;30(5):599–609. doi:10.1111/j.1468-2982.2009.01941.x - DOI - PubMed
    1. Pradeep R, Nemichandra SC, Harsha S, Radhika K. Migraine disability, quality of life, and its predictors. Ann Neurosci. 2020;27(1):18–23. doi:10.1177/0972753120929563 - DOI - PMC - PubMed
    1. Negro A, Martelletti P. Chronic migraine plus medication overuse headache: two entities or not? J Headache Pain. 2011;12(6):593–601. doi:10.1007/s10194-011-0388-3 - DOI - PMC - PubMed
    1. Bloudek LM, Stokes M, Buse DC, et al. Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS). J Headache Pain. 2012;13(5):361–378. doi:10.1007/s10194-012-0460-7 - DOI - PMC - PubMed