Neuromuscular Omnicentre, Neurorehabilitation Unit, University of Milan, Niguarda Hospital, Milan, Italy.
Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA.
Muscle Nerve. 2021 Sep;64(3):342-346. doi: 10.1002/mus.27354. Epub 2021 Jul 9.
INTRODUCTION/AIM: Long-term efficacy and safety of dichlorphenamide (DCP) were characterized in patients with primary periodic paralysis (PPP).
Patients with PPP in a double-blind, placebo-controlled study were randomly assigned to receive DCP 50 mg twice daily or placebo for 9 weeks, followed by a 52-week open-label DCP treatment phase (DCP/DCP and placebo/DCP populations). Efficacy (attack rate, severity-weighted attack rate) and safety were assessed in patients completing the study (61 weeks). In this post hoc analysis, efficacy and safety data were pooled from hyperkalemic and hypokalemic substudies.
Sixty-three adults (age, 19-76 years) completed the double-blind phase; 47 (74.6%) of these patients completed 61 weeks. There were median decreases in weekly attack and severity-weighted attack rates from baseline to week 61 (DCP/DCP [n = 25], -1.00 [P < .0001]; placebo/DCP [n = 20], -0.63 [P = .01] and DCP/DCP, -2.25 [P < .0001]; placebo/DCP, -1.69 [P = .01]). Relatively smaller median decreases in weekly attack and severity-weighted attack rates occurred from weeks 9 to 61 among patients receiving DCP continuously (n = 26; -0.14 [P = .1] and -0.24 [P = .09]) than among those switching from placebo to DCP after 9 weeks (n = 16; -1.04 [P = .049] and -2.72 [P = .08]). Common adverse events (AEs) were paresthesia and cognition-related events, which typically first occurred within 1 month of blinded treatment initiation and in rare cases led to treatment discontinuation. Dose reductions were frequently associated with common AE resolution.
One-year open-label DCP treatment after a 9-week randomized, controlled study confirmed long-term DCP remains safe and effective for chronic use. Tolerability issues (paresthesia, cognition-related AEs) were manageable in most patients.
介绍/目的：在原发性周期性麻痹（PPP）患者中，对二氯苯酰胺（DCP）的长期疗效和安全性进行了描述。
在一项双盲、安慰剂对照的研究中，将 PPP 患者随机分为每日两次接受 DCP 50mg 或安慰剂治疗 9 周，随后进行为期 52 周的开放性 DCP 治疗阶段（DCP/DCP 和安慰剂/DCP 人群）。在完成研究（61 周）的患者中评估疗效（发作率、严重程度加权发作率）和安全性。在这项事后分析中，从高钾血症和低钾血症亚研究中汇集了疗效和安全性数据。
63 名成年人（年龄 19-76 岁）完成了双盲阶段；其中 47 名（74.6%）患者完成了 61 周。与基线相比，第 61 周时每周发作和严重程度加权发作率中位数均有下降（DCP/DCP [n=25]，-1.00[P<0.0001]；安慰剂/DCP [n=20]，-0.63[P=0.01]和 DCP/DCP，-2.25[P<0.0001]；安慰剂/DCP，-1.69[P=0.01]）。持续接受 DCP 治疗的患者（n=26）从第 9 周至第 61 周每周发作和严重程度加权发作率中位数相对较小的下降（-0.14[P=0.1]和-0.24[P=0.09]），而在第 9 周后从安慰剂转换为 DCP 的患者（n=16）则较大（-1.04[P=0.049]和-2.72[P=0.08]）。常见不良事件（AE）为感觉异常和认知相关事件，这些事件通常在接受盲法治疗后 1 个月内首次发生，极少数情况下导致治疗中断。减少剂量通常与常见 AE 缓解相关。
在一项为期 9 周的随机对照研究之后，进行为期 1 年的开放性 DCP 治疗，证实长期使用 DCP 对慢性使用仍然是安全有效的。大多数患者能够耐受（感觉异常、认知相关的 AE）问题。
