Efficacy of Erenumab for Migraine Prevention in Japanese Patients with Episodic and Chronic Migraine: Results of a Post-Hoc Pooled Analysis

Abstract

Introduction: Erenumab, a fully human monoclonal antibody against the calcitonin gene-related peptide receptor, is approved in Japan for the prevention of adult migraine. This post-hoc analysis evaluated the efficacy of erenumab in Japanese patients with low-frequency episodic migraine (LFEM) versus those with high-frequency episodic migraine (HFEM) and chronic migraine (CM).

Methods: A pooled analysis of data from the 24-week double-blind treatment phases (DBTPs) of phase 2 and 3 studies evaluated the efficacy of once-monthly erenumab 70 mg in Japanese patients. Patients were categorized into subgroups by monthly migraine days (MMD): LFEM and HFEM/CM. The main efficacy outcomes were change from baseline in MMD, acute migraine-specific medication treatment days (MSMD), and six-item Headache Impact Test (HIT-6™) scores.

Results: Patients with migraine (n = 532) were included in the analysis (LFEM, n = 215; HFEM, n = 215; CM, n = 102). Overall, mean age was 44 years, 86.5% were female, and 63.3-88.2% had used or were taking migraine preventive treatment at baseline. Throughout the DBTP, the placebo-adjusted mean change from baseline in MMD, MSMD, and HIT-6 scores with erenumab was similar across LFEM and HFEM/CM subgroups. The proportion of patients achieving at least 50% or 75% reduction from baseline in MMD and MSMD was similar across migraine frequency groups. Reduction in MMD moderately correlated with improvement in HIT-6 scores in the LFEM and HFEM/CM groups. Furthermore, the proportion of patients converting from HFEM/CM to LFEM during the DBTP was higher in the erenumab group than in the placebo.

Conclusion: In Japanese patients with different migraine frequencies, erenumab treatment resulted in significant improvements in MMD, MSMD, and headache impact. This pooled analysis of data from phase 2 and 3 studies increases confidence that erenumab is efficacious in patients with high MMD, which is associated with increased disability.

Keywords: Chronic migraine; Erenumab; High frequency episodic migraine; Japan.

Conflict of interest statement

Shigekazu Kitamura and Takao Takeshima have nothing to disclose that could be construed as a conflict of interest. Reija Koukakis, Daishi Yui, Gabriel Paiva da Silva Lima, Cheng Peng, Ryuji Yoshida, Yotari Numachi, and Miki Hasebe are/were employees of Amgen. Reija Koukakis, Daishi Yui, Gabriel Paiva da Silva Lima, and Miki Hasebe disclose ownership of Amgen stock. Ryuji Yoshida is now affiliated with UCB Japan (Tokyo, Japan) and Yotaro Numachi is affiliated with Yu Mental Clinic (Tokyo, Japan).

© 2023. The Author(s).

Figures

Fig. 1

Study designs for the phase 2 and phase 3 studies aF/U visit was 16 weeks after the last dose of the IP for the phase 2 study and 12 weeks after the last dose of the IP for the phase 3 study. Only patients receiving ≥ 1 dose of erenumab 70 mg (orange boxes) or placebo (blue boxes) were included in the analysis. CM chronic migraine, DBTP double-blind treatment phase, EM episodic migraine, F/U follow-up, HFEM high-frequency episodic migraine, IP investigational product, LFEM low-frequency episodic migraine, MMD monthly migraine days, OLTP open-label treatment phase, QM once monthly, SC subcutaneous

Fig. 2

LSM change from baseline in MMD during the DBTP. LSM is from an adjusted analysis utilizing a generalized linear mixed model, which includes treatment, visit, treatment-by-visit interaction, stratification factors of study (20120309 or 20170609) and prior migraine preventive treatment status (ever used or never used), and baseline value as covariates and assumes a first-order autoregression covariance structure. Nominal P values are shown without multiplicity adjustment. Δ, difference in treatment effect (erenumab 70 mg—placebo). Numbers in parentheses are the 95% CI values for the difference in treatment effect between erenumab 70 mg and placebo. Error bars represent SE. CI confidence interval, CM chronic migraine, DBTP double-blind treatment phase, HFEM high-frequency episodic migraine, LFEM low-frequency episodic migraine, LSM least-squares mean, MMD monthly migraine days, SE standard error of the mean

Fig. 3

Proportion of patients achieving ≥ 50% and ≥ 75% reduction from baseline in MMD over months 4–6 of the DBTP. Common ORs and P values were obtained from a Cochran–Mantel–Haenszel test, stratified by stratification factors of study (20120309 or 20170609) and prior preventive treatment status (ever or never). Nominal P values were used for pairwise comparison without multiplicity adjustment. The P values for Breslow–Day tests of homogeneity of ORs across strata for ≥ 50% responders were 0.2 for LFEM and 0.7 for HFEM/CM, and for ≥ 75% responders were 0.9 for LFEM and 0.4 for HFEM/CM. CI confidence interval, CM chronic migraine, DBTP double-blind treatment phase, HFEM high-frequency episodic migraine, LFEM low-frequency episodic migraine, MMD monthly migraine days, OR odds ratio

Fig. 4

Scatter plot of change from baseline in mean MMD and mean HIT-6 scores over months 4–6 in individual patients treated with erenumab 70 mg. Pearson correlation analysis was carried out. The teal and blue dots represent patients with LFEM and HFEM/CM, respectively. CM chronic migraine, HFEM high-frequency episodic migraine, HIT-6 six-item Headache Impact test, LFEM low-frequency episodic migraine, MMD monthly migraine days, r Pearson correlation coefficient

Fig. 5

Conversion from one migraine class at baseline to another during the DBTP. (A) HFEM/CM to LFEM and (B) LFEM to HFEM/CM. CM chronic migraine, DBTP double-blind treatment phase, HFEM high-frequency episodic migraine, LFEM low-frequency episodic migraine