Long-term efficacy and safety of dichlorphenamide for treatment of primary periodic paralysis.
Long-term efficacy and safety of dichlorphenamide for treatment of primary periodic paralysis.
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研究了二氯苯胺（DCP）在原发性周期性麻痹（PPP）患者中的长期疗效和安全性。在一项双盲安慰剂对照研究中，PPP患者被随机分配接受DCP 50 mg，每日两次或安慰剂治疗，为期9周，随后是52周的开放标签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、严重加权发作率）和安全性。在这个事后分析中，疗效和安全性数据来自高钾和低钾亚研究。63名成人（年龄19 - 76岁）完成了双盲阶段；其中47例（74.6%）患者完成61周治疗。从基线到第61周，周发作率和严重加权发作率中位数下降（DCP/DCP [n = 25], - 1.00 [P < .0001]；安慰剂/DCP [n = 20], - 0.63 [P = .01]; DCP/DCP, - 2.25 [P < .0001]；安慰剂/DCP， - 1.69 [P = .01]）。连续接受DCP的患者（n = 26; - 0.14 [P = 0.1]和- 0.24 [P = .09]）在第9周至第61周的周发作率和严重程度加权发作率的中位数下降幅度相对较小，而在第9周后从安慰剂切换到DCP的患者（n = 16; - 1.04 [P = .049]和- 2.72 [P = .08]）。常见的不良事件（ae）是感觉异常和认知相关事件，通常首次发生在盲法治疗开始后1个月内，在极少数情况下导致治疗停止。剂量减少通常与常见的AE消退有关。一项为期9周的随机对照研究证实，长期使用DCP对慢性患者仍然安全有效。大多数患者的耐受性问题（感觉异常、认知相关不良事件）是可控的。
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.