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罗氟司特乳膏治疗慢性斑块型银屑病安全有效
作者:小柯机器人 发布时间:2022/9/22 20:17:22

美国西奈山伊坎医学院Mark G. Lebwohl团队比较了罗氟司特乳膏与赋形剂治疗慢性斑块型银屑病的疗效与安全性。该项研究成果发表在2022年9月20日出版的《美国医学会杂志》上。

在银屑病患者的2b期临床试验中,每日一次的罗氟司特乳膏(0.3%,一种有效的磷酸二酯酶4抑制剂)显示出疗效,并且耐受性良好。该研究旨在评价0.3%罗氟司特乳膏在2个斑块型银屑病患者试验中的疗效,每天一次,持续8周。

两个临床3期、随机、双盲、对照、多中心试验(DERMIS-1[试验1;n = 439]和DERMIS-2[试验2;n = 442])分别于2019年12月9日至2020年11月16日、2019年11月9日至2020年11月月23日在美国和加拿大的40个中心(试验1)和39个中心(实验2)进行。招募2岁及以上、皮损占体表面积的2%至20%的斑块型银屑病患者。试验1和试验2的最终随访日期分别为2020年11月20日和2020年11月23日。将患者按2:1的比例随机分配,分别接受0.3%罗氟司特乳膏(试验1:286例;试验2:290例)或赋形剂(试验1:153例;试验2:152例),每天一次,持续8周。

主要疗效终点是第8周时研究者全球评估(IGA)成功(清除或几乎清除状态,且与基线相比提高2级及以上[分数范围,0-4]),采用Cochran-Mantel-Haenszel检验进行分析,按部位、基线IGA评分和病变累及程度分层。有9个次要结局,包括关节间IGA成功,银屑病面积和严重性指数(PASI)得分降低75%,最严重瘙痒数字评分量表得分在基线检查时达到4分或更高,在第8周达到4分(WI-NRS成功)(评分:0分[无瘙痒]到10分[最严重的可想象瘙痒];最小临床重要差异,4分)。

在881名受试者(平均年龄为47.5岁;女性320人[36.3%])中,试验1中罗氟司特组和赋形剂组的IGA平均得分均为2.9,试验2中罗氟司特组和赋形剂组的IGA平均得分亦均为2.9。在统计学上,罗氟司特组患者在第8周IGA成功率显著高于赋形剂组患者(试验1:42.4%比6.1%;试验2:37.5%比6.9%;组间差异显著)。

在9个次要终点中,试验1的8个和试验2的9个观察到与赋形剂相比有利于罗氟司特的统计学显著差异,包括关节间IGA成功率(71.2%比13.8%;68.1%比18.5%),PASI得分降低75%(41.6%比7.6%;39.0%比5.3%),WI-NRS成功率(67.5%比26.8%;69.4%比35.6%)。试验1中罗氟司特组治疗引发不良事件的发生率为25.2%,赋形剂组为23.5%,试验2组分别为25.9%与18.4%。试验1中罗氟司特组的严重不良事件发生率为0.7%,试验2中亦为0.7%。

研究结果表明,对于慢性斑块型银屑病患者,与赋形剂相比,0.3%罗氟司特乳膏治疗8周后的临床状况更好。仍需进一步研究,以评估与其他积极治疗相比的疗效,并评估长期疗效和安全性。

附:原文原文

Title: Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials

Author: Mark G. Lebwohl, Leon H. Kircik, Angela Y. Moore, Linda Stein Gold, Zoe D. Draelos, Melinda J. Gooderham, Kim A. Papp, Jerry Bagel, Neal Bhatia, James Q. Del Rosso, Laura K. Ferris, Lawrence J. Green, Adelaide A. Hebert, Terry Jones, Steven E. Kempers, David M. Pariser, Paul S. Yamauchi, Matthew Zirwas, Lorne Albrecht, Alim R. Devani, Mark Lomaga, Amy Feng, Scott Snyder, Patrick Burnett, Robert C. Higham, David R. Berk

Issue&Volume: 2022/09/20

Abstract:

Importance  Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis.

Objective  To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis.

Design, Setting, and Participants  Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n=439] and DERMIS-2 [trial 2; n=442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively.

Interventions  Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n=286; trial 2: n=290), or vehicle cream (trial 1: n=153; trial 2: n=152) once daily for 8 weeks.

Main Outcomes and Measures  The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points).

Results  Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P<.001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P<.001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P<.001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P<.001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2.

Conclusions and Relevance  Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety.

DOI: 10.1001/jama.2022.15632

Source: https://jamanetwork.com/journals/jama/article-abstract/2796379

期刊信息

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex