3,4-Diaminopyridine safety in clinical practice: an observational, retrospective cohort study
3,4-Diaminopyridine safety in clinical practice: an observational, retrospective cohort study
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DOI：
10.1007/s00415-009-5442-6
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发表时间：
2010-06-01
影响因子：
6
通讯作者：
Edan, Gilles
中科院分区：
文献类型：
--
作者：
Flet, Laurent;Polard, Elisabeth;Edan, Gilles
疲劳是多发性硬化症 (MS) 最常见和致残的症状之一，对患者的生活质量具有重大但往往被低估的影响。目前的治疗主要是对症治疗。 3,4-二氨基吡啶 (3,4-DAP) 是一种电压依赖性钾通道阻滞剂，多年来已在欧洲以指定患者为基础使用，以改善多发性硬化症和其他神经肌肉疾病患者的运动功能和疲劳，并且正在接受欧洲针对兰伯特-伊顿肌无力综合征 (LEMS) 的批准程序。 3,4-DAP 作为多发性硬化症对症治疗的疗效和安全性尚未得到广泛评估。本研究旨在通过观察性、回顾性研究评估 3,4-DAP 在常规临床实践中的安全性。该研究涉及法国雷恩多发性硬化症诊所的 669 名患者，他们在 1998 年至 2003 年期间接受 3,4-DAP 治疗以缓解疲劳。总体而言，18.2% 的患者在使用中等剂量的 3,4-DAP（LEMS 患者每天 20-30 毫克，或每天 80 毫克）长达 51 个月期间出现药物不良反应 (ADR)。大多数不良反应是轻度至中度的，在治疗结束时（平均治疗持续时间=两个月）或剂量调整后是短暂的或可逆的。大多数不需要停药。最常见的不良反应是感觉异常。其中一例癫痫发作、一例肝毒性和一例心悸被认为“可能”与 3,4-DAP 有关。这些强调了在 3,4-DAP 治疗期间持续监测的必要性。
Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS) and has a significant, often underestimated, impact on patients' quality of life. Current management is mainly symptomatic. 3,4-diaminopyridine (3,4-DAP) is a voltage-dependent potassium channel blocker that has been used on a named patient basis in Europe for many years to improve motor function and fatigue in patients with MS and other neuromuscular disorders, and it is undergoing the European approval process for Lambert-Eaton myasthenic syndrome (LEMS). The efficacy and safety of 3,4-DAP as symptomatic therapy in MS have not been widely evaluated. This study aimed to assess the safety profile of 3,4-DAP in routine clinical practice in an observational, retrospective study. The study involved 669 patients of the Rennes Multiple Sclerosis Clinic, France, who were treated with 3,4-DAP for the relief of fatigue during the period 1998-2003. Overall, 18.2% of patients presented adverse drug reactions (ADRs) while using moderate doses of 3,4-DAP (20-30 mg daily or up to 80 mg daily for patients with LEMS) for periods of up to 51 months. The majority of ADRs were mild to moderate and transient or reversible at the end of treatment (mean treatment duration = two months) or after dose adjustment. Most did not require discontinuation. The most commonly observed ADRs were paraesthesias. There was one case of epileptic seizure, one of hepatotoxicity and one of heart palpitations thought 'possibly' to be linked to 3,4-DAP. These underline the need for continued monitoring during treatment with 3,4-DAP.