Muth Carolin, Teufel Julian, Schöls Ludger, Synofzik Matthis, Franke Christiana, Timmann Dagmar, Mansmann Ulrich, Strupp Michael
Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.
Neurol Clin Pract. 2021 Aug;11(4):e438-e446. doi: 10.1212/CPJ.0000000000001017.
To determine the efficacy and safety of the treatment with prolonged-release 4-aminopyridine (fampridine) and acetazolamide for patients with episodic ataxia type 2 (EA2), patients with EA2 were treated with a random sequence of fampridine, acetazolamide, and placebo in a 3-period crossover trial.
A total of 30 patients with EA2 (8 female; aged 20-71 years; 18 genetically confirmed, 4 with a positive family history, 8 with the clinical diagnosis) were enrolled in this phase III, randomized, double-blind, placebo-controlled, 3-period crossover trial. Each period lasted 12 weeks with a 4-week washout period. Each patient received a random sequence of 20 mg/d fampridine, 750 mg/d acetazolamide, and placebo. The primary end point was the number of attacks during the last 30 days within the 12-week treatment period. Participants, caregivers, and those assessing the outcomes were blinded to the intervention.
Compared with placebo, fampridine reduced the number of attacks to 63% (95% CI 54%-74%) and acetazolamide to 52% (95% CI 46%-60%). A total of 39 (26.5%) adverse events were observed under treatment with fampridine (mostly tingling paresthesia and fatigue), 66 (44.9%) happened under acetazolamide (mostly taste disturbance and gastrointestinal complaints), and 42 (28.6%) under placebo (mostly gastrointestinal complaints).
Both fampridine and acetazolamide significantly reduce the number of attacks in patients with EA2 and related EA in comparison to placebo. Fampridine 10 mg twice daily had fewer side effects than acetazolamide 250 mg 3 times daily. The trial was registered with DRKS.de (DRKS00005258) and EudraCT (2013-000107-17). This study was supported by the Federal Ministry of Education and Research (BMBF) (grant number 01EO0901). Fampridine (study medication) was provided by Biogen Idec.
Class II evidence.
确定缓释4-氨基吡啶（法吡拉定）和乙酰唑胺治疗2型发作性共济失调（EA2）患者的疗效和安全性，在一项为期3个阶段的交叉试验中，EA2患者按随机顺序接受法吡拉定、乙酰唑胺和安慰剂治疗。
总共30例EA2患者（8例女性；年龄20 - 71岁；18例经基因确诊，4例有阳性家族史，8例临床诊断）纳入了这项III期随机、双盲、安慰剂对照、3阶段交叉试验。每个阶段持续12周，有4周的洗脱期。每位患者按随机顺序接受20mg/d法吡拉定、750mg/d乙酰唑胺和安慰剂治疗。主要终点是12周治疗期内最后30天的发作次数。参与者、照料者和评估结果的人员对干预措施不知情。
与安慰剂相比，法吡拉定使发作次数减少至63%（95%CI 54% - 74%），乙酰唑胺使发作次数减少至52%（95%CI 46% - 60%）。法吡拉定治疗期间共观察到39例（26.5%）不良事件（主要是刺痛性感觉异常和疲劳），乙酰唑胺治疗期间发生66例（44.9%）（主要是味觉障碍和胃肠道不适），安慰剂治疗期间发生42例（28.6%）（主要是胃肠道不适）。
与安慰剂相比，法吡拉定和乙酰唑胺均能显著减少EA2患者及相关EA患者的发作次数。每日2次服用10mg法吡拉定的副作用比每日3次服用250mg乙酰唑胺更少。该试验已在DRKS.de（DRKS00005258）和EudraCT（2013 - 000107 - 17）注册。本研究由联邦教育与研究部（BMBF）资助（资助编号01EO090）。法吡拉定（研究药物）由百健艾迪公司提供。
II级证据。
