Department of Dermatology, Center for Chronic Pruritus, University Hospital, Münster, Germany.
Therapeutics Clinical Research, San Diego, California, USA.
J Eur Acad Dermatol Venereol. 2022 Aug;36(8):1308-1317. doi: 10.1111/jdv.18170. Epub 2022 May 6.
Once-daily abrocitinib treatment provided meaningful improvements in signs and symptoms of moderate-to-severe atopic dermatitis (AD) in randomized controlled studies.
To evaluate proportions of patients with responses meeting higher threshold efficacy responses than commonly used efficacy end points and to determine if these responses were associated with quality-of-life (QoL) benefits.
Data from a phase 2b (NCT02780167) and two phase 3 studies (NCT03349060/JADE MONO-1; NCT03575871/JADE MONO-2) in adult and adolescent patients (N = 942) with moderate-to-severe AD receiving once-daily abrocitinib 200 mg, abrocitinib 100 mg or placebo were pooled. Commonly used (Eczema Area and Severity Index [EASI]-75 and ≥4-point improvement in Pruritus Numerical Rating Scale [PP-NRS4]) and higher threshold efficacy end points (EASI-90 to <EASI-100, EASI-100 or PP-NRS0/1 response) were evaluated. Proportions of patients across Children's Dermatology Life Quality Index/Dermatology Life Quality Index (CDLQI/DLQI) band descriptors who achieved various efficacy end points were analysed.
More abrocitinib-treated patients achieved commonly used or higher threshold efficacy end points at week 12 vs. placebo. More abrocitinib-treated patients who achieved higher threshold efficacy end points reported 'no effect' of AD on QoL (by CDLQI/DLQI) at week 12 vs. those who achieved commonly used but not higher threshold efficacy end points (PP-NRS0/1 vs. PP-NRS4 but not PP-NRS0/1 responders [200 mg: 66.3% vs. 17.5%; 100 mg: 62.1% vs. 20.0%]; EASI-100, EASI-90 to <EASI-100 vs. EASI-75 to <EASI-90 responders [200 mg: 67.6%, 48.9% vs. 28.8%; 100 mg: 63.2%, 48.1% vs. 36.7%]).
Substantial proportions of patients with moderate-to-severe AD receiving abrocitinib met higher threshold efficacy end points, and this was associated with meaningful additional QoL benefits compared with those who did not meet these higher efficacy thresholds. Not only do a substantial proportion of abrocitinib-treated patients achieve higher threshold efficacy end points but they also do so in a similar timeframe as the more commonly used thresholds for efficacy end points.
NCT02780167, NCT03349060 and NCT03575871.
在随机对照研究中，每日一次阿布昔替尼治疗可显著改善中重度特应性皮炎（AD）的体征和症状。
评估达到比常用疗效终点更高阈值疗效反应的患者比例，并确定这些反应是否与生活质量（QoL）获益相关。
来自 2 项 2b 期（NCT02780167）和 2 项 3 期研究（NCT03349060/JADE MONO-1；NCT03575871/JADE MONO-2）的数据，共纳入 942 例接受每日一次阿布昔替尼 200mg、阿布昔替尼 100mg 或安慰剂治疗的中重度 AD 成年和青少年患者。评估了常用（湿疹面积和严重程度指数[EASI]-75 和瘙痒数字评分量表[PP-NRS4]改善≥4 分）和更高阈值疗效终点（EASI-90 至＜EASI-100、EASI-100 或 PP-NRS0/1 反应）。分析了在儿童皮肤病生活质量指数/皮肤病生活质量指数（CDLQI/DLQI）各波段描述中达到各种疗效终点的患者比例。
与安慰剂相比，更多接受阿布昔替尼治疗的患者在第 12 周达到了常用或更高阈值的疗效终点。与达到常用但未达到更高阈值疗效终点的患者相比，达到更高阈值疗效终点的阿布昔替尼治疗患者报告 AD 对 QoL 的“无影响”（通过 CDLQI/DLQI），第 12 周更高阈值疗效终点的患者比例更高（PP-NRS0/1 比 PP-NRS4 但非 PP-NRS0/1 应答者[200mg：66.3%比 17.5%；100mg：62.1%比 20.0%]；EASI-100、EASI-90 至＜EASI-100 比 EASI-75 至＜EASI-90 应答者[200mg：67.6%、48.9%比 28.8%；100mg：63.2%、48.1%比 36.7%]）。
接受阿布昔替尼治疗的中重度 AD 患者中有相当比例达到了更高阈值的疗效终点，与未达到这些更高疗效阈值的患者相比，这与更显著的额外 QoL 获益相关。不仅相当比例的阿布昔替尼治疗患者达到了更高阈值的疗效终点，而且他们在与更常用的疗效终点类似的时间内达到了这些终点。
NCT02780167、NCT03349060 和 NCT03575871。
