Kimura Yoshiyuki, Yamaguchi Shigeki, Suzuki Takahiro, Kato Jitsu, Chiba Satoko, Hirakawa Naomi, Yamaguchi Keisuke, Tanabe Yutaka, Takatsuna Hiroshi, Kenyoshi Yusuke, Shiosakai Kazuhito, Sakai Miyoshi, Iseki Masako
Department of Anesthesiology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi, 321-0293, Japan.
Department of Anesthesiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.
Pain Ther. 2021 Jun;10(1):711-727. doi: 10.1007/s40122-021-00255-y. Epub 2021 Apr 15.
Mirogabalin, which is a selective ligand of the αδ subunit of voltage-gated Ca channels, was recently approved in Japan for peripheral neuropathic pain. The αδ ligands, including mirogabalin and pregabalin, are associated with significant risk of adverse events (AEs) such as somnolence or dizziness, leading to poor compliance and subsequent inefficacy. Safety and efficacy data for switching patients from pregabalin to mirogabalin are scarce.
This prospective, single-arm, open-label study involving ten participating centers in Japan recruited patients aged ≥ 20 years with peripheral neuropathic pain [visual analog scale (VAS) score ≥ 40 mm]. Where necessary, patients underwent a 1-week tapering period to reduce their pregabalin dose, after which pregabalin was stopped and mirogabalin dose was increased using a step-wise dose titration. Patients underwent dose increases after the first and second weeks if there were no tolerability issues, followed by the effective doses until the end of the study (4 weeks). The primary endpoint was the incidence of somnolence, dizziness, and peripheral edema; secondary endpoints included changes in VAS score. AEs were monitored for safety.
Of 157 patients who provided informed consent, 152 patients were enrolled; 136 (89.5%) patients completed the study. The overall incidences of somnolence, dizziness, and peripheral edema were 41.4, 15.8, and 2.6%, respectively. Most patients (> 70%) experienced mild AEs, and one patient experienced a severe AE (dizziness). Most patients (> 70%) were able to achieve dose titration to an effective dose. Overall mean VAS score significantly decreased (Δ15.7 mm, p < 0.0001) by the end of the study.
Mirogabalin switching from pregabalin is well tolerated and effective in pain management for peripheral neuropathic pain using a step-wise titration.
Japan Registry of Clinical Trials (jRCTs031190113).
米罗加巴林是电压门控钙通道αδ亚基的选择性配体，最近在日本被批准用于治疗周围神经性疼痛。包括米罗加巴林和普瑞巴林在内的αδ配体与嗜睡或头晕等不良事件（AE）的显著风险相关，导致依从性差及随后的治疗无效。关于将患者从普瑞巴林转换为米罗加巴林的安全性和有效性数据很少。
这项前瞻性、单臂、开放标签研究在日本的10个参与中心进行，招募年龄≥20岁、患有周围神经性疼痛[视觉模拟量表（VAS）评分≥40mm]的患者。必要时，患者进行为期1周的剂量递减期以减少其普瑞巴林剂量，之后停用普瑞巴林，并使用逐步剂量滴定法增加米罗加巴林剂量。如果没有耐受性问题，患者在第1周和第2周后增加剂量，随后直至研究结束（4周）均使用有效剂量。主要终点是嗜睡、头晕和外周水肿的发生率；次要终点包括VAS评分的变化。监测不良事件以确保安全性。
在157名提供知情同意的患者中，152名患者入组；136名（89.5%）患者完成了研究。嗜睡、头晕和外周水肿的总体发生率分别为41.4%、15.8%和2.6%。大多数患者（>70%）经历轻度不良事件，1名患者经历严重不良事件（头晕）。大多数患者（>70%）能够实现剂量滴定至有效剂量。到研究结束时，总体平均VAS评分显著降低（Δ15.7mm，p<0.0001）。
从普瑞巴林转换为米罗加巴林耐受性良好，且使用逐步滴定法在周围神经性疼痛的疼痛管理中有效。
日本临床试验注册中心（jRCTs031190113）。
