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Randomized Controlled Trial
. 2021 Dec;44(12):1355-1364.
doi: 10.1007/s40264-021-01119-2. Epub 2021 Oct 23.

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

Fumihiko Sakai  1 , Norihiro Suzuki  2 , Xiaoping Ning  3 , Miki Ishida  4 , Chiharu Usuki  4 , Katsuhiro Iba  4 , Yuki Isogai  5 , Nobuyuki Koga  6
Affiliations
Randomized Controlled Trial

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

Fumihiko Sakai et al. Drug Saf. 2021 Dec.

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.

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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.

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
See this image and copyright information in PMC

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