Effects of Fremanezumab on Medication Overuse in Japanese Chronic Migraine Patients: Post Hoc Analysis of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Noboru Imai; Yuki Isogai; Yoshiyuki Shibasaki; Masami Nakai; Miki Ishida; Xiaoping Ning; Nobuyuki Koga

doi:10.1007/s40120-023-00531-3

Effects of Fremanezumab on Medication Overuse in Japanese Chronic Migraine Patients: Post Hoc Analysis of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Neurol Ther. 2023 Dec;12(6):1981-1991. doi: 10.1007/s40120-023-00531-3. Epub 2023 Sep 11.

Authors

Noboru Imai¹, Yuki Isogai², Yoshiyuki Shibasaki³, Masami Nakai⁴, Miki Ishida⁴, Xiaoping Ning⁵, Nobuyuki Koga⁶

Affiliations

¹ Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan.
² Medical Affairs, Otsuka Pharmaceutical Co., Ltd, 16-4 Kounan 2-Chome, Minatoku, Tokyo, 108-8242, Japan. isogai@otsuka.jp.
³ Medical Affairs, Otsuka Pharmaceutical Co., Ltd, 16-4 Kounan 2-Chome, Minatoku, Tokyo, 108-8242, Japan.
⁴ Otsuka Pharmaceutical Co., Ltd, Osaka, Japan.
⁵ Teva Branded Pharmaceutical Products R&D, Inc, West Chester, PA, USA.
⁶ Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan.

Abstract

Introduction: Chronic migraine (CM) patients commonly take acute headache medications, often resulting in medication overuse (MO). This post hoc analysis evaluated the efficacy of fremanezumab in CM patients from Japan with and without MO, which is not yet established.

Methods: A multicenter, double-blind, parallel-group, phase 2b/3 trial randomized patients (1:1:1) to monthly fremanezumab via subcutaneous injection (initial dose: 675 mg, second/third doses: 225 mg), quarterly fremanezumab (initial dose: 675 mg, second/third doses: placebo), or placebo for 3 months. This post hoc analysis analyzed data from Japanese patients with and without MO (monthly use of acute headache medication ≥ 15 days, migraine-specific acute medication ≥ 10 days, or combination medication ≥ 10 days). Outcomes included the original primary endpoint of average headache days of moderate or greater severity per month (HDs), the proportion of patients with ≥ 50% reduction in HDs and the proportion of patients changing status from with to without MO.

Results: Of 479 patients enrolled, 320 (66.8%) had baseline MO. Monthly average HDs were significantly reduced versus placebo with fremanezumab in both patients with MO (mean [standard error] difference vs. placebo: monthly - 2.0 [0.6], p = 0.0012; quarterly - 1.8 [0.6], p = 0.0042) and without MO (- 1.6 [0.8], p = 0.0437; - 1.5 [0.8], p = 0.0441). Significantly more fremanezumab-treated patients with MO (monthly 28/108 [25.9%], p = 0.0040 quarterly 25/99 [25.3%], p = 0.0070) or without MO (18/50 [36.0%], p = 0.0132; and 21/60 [35.0%], p = 0.0126) had ≥ 50% reduction in HDs versus placebo (12/111 [10.8%] and 7/49 [14.3%], respectively). A significantly greater proportion of fremanezumab-treated patients reverted to no MO (monthly 50/108 [46.3%], p = 0.0115; quarterly 44/99 [44.4%], p = 0.0272) vs. placebo (33/111 [29.7%]).

Conclusion: Fremanezumab appears effective as preventive migraine treatment in Japanese CM patients with or without MO while also being beneficial in reducing MO.

Keywords: Calcitonin gene-related peptide; Chronic migraine; Fremanezumab; Japanese; Medication overuse.