Journal of the American Academy of Dermatology ( IF 12.8 ) Pub Date : 2018-07-10 , DOI: 10.1016/j.jaad.2018.07.002 Dee Anna Glaser , Adelaide A. Hebert , Alexander Nast , William P. Werschler , Lawrence Green , Richard Mamelok , Janice Drew , John Quiring , David M. Pariser
Background
Glycopyrronium tosylate (GT) is a topical anticholinergic developed for once-daily treatment of primary axillary hyperhidrosis.
Objective
Assess the efficacy and safety of GT for primary axillary hyperhidrosis.
Methods
ATMOS-1 and ATMOS-2 were replicate randomized, double-blind, vehicle-controlled, 4-week phase 3 trials. Patients were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4 weeks. Coprimary endpoints were responder rate (≥4-point improvement from baseline) on item 2 (severity of sweating) of the Axillary Sweating Daily Diary (ASDD), which is a newly developed patient-reported outcome measure, and absolute change from baseline in axillary gravimetric sweat production at week 4. Safety evaluation included treatment-emergent adverse events.
Results
Pooled data, which are consistent with the individual trial results, show that significantly more GT-treated patients achieved an ASDD-Item 2 response than did those treated with vehicle (59.5% vs 27.6%), and they had reduced sweat production from baseline (–107.6 mg/5 min vs –92.1 mg/5 min) at week 4 (P < .001 for both coprimary end points). Most treatment-emergent adverse events were mild or moderate and infrequently led to discontinuation.
Limitations
Short trial duration and inherent challenges in gravimetrically assessing sweat production.
Conclusions
GT applied topically on a daily basis over 4 weeks reduced the severity of sweating as measured by ASDD-Item 2, reduced sweat production as measured gravimetrically, and was generally well tolerated in patients with primary axillary hyperhidrosis.
中文翻译:
局部使用甲苯磺酸格隆铵治疗原发性腋窝多汗症:ATMOS-1和ATMOS-2 3期随机对照试验的结果
背景
甲苯磺酸格隆铵(GT)是一种局部抗胆碱能药,每天一次用于治疗原发性腋窝多汗症。
客观的
评估GT治疗原发性腋窝多汗症的疗效和安全性。
方法
ATMOS-1和ATMOS-2是重复随机,双盲,载体对照,为期4周的3期临床试验。患者按2:1的比例随机分配至3.75%的GT或媒介物,每天一次,每次腋窝一次,持续4周。首要研究终点是腋窝出汗每日日记(ASDD)的第2项(出汗严重程度)的缓解率(比基线提高4分以上),这是一项新近开发的患者报告的结局指标,而腋窝自基线起的绝对变化在第4周时发生重量汗水产生。安全性评估包括治疗紧急不良事件。
结果
汇总的数据与单独的试验结果一致,结果表明,接受GT治疗的患者实现ASDD-Item 2应答的人数明显多于接受载体治疗的患者(59.5%比27.6%),并且他们的出汗量比基线减少(在第4周时为–107.6 mg / 5分钟,而–92.1 mg / 5分钟( 两个主要主要终点的P <.001)。大多数出现治疗的不良事件是轻度或中度的,很少导致停药。
局限性
用重量分析法评估汗液产生的试验时间短且存在固有的挑战。
结论
按ASDD-Item 2的规定,每天局部使用GT可以降低出汗的严重程度(按ASDD-Item 2的测定),可以减少出汗的量(按重量分析),并且在原发性腋窝多汗症患者中一般耐受性良好。