Supplementary Material for: Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated With Improved Quality of Life Outcomes in Adult and Adolescent Patients With Moderate-to-Severe Atopic Dermatitis

Background: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden.
Objectives: To evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD.
Methods: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item (“How painful was your skin over the past 24 hours?”) on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children’s Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed effects repeated measures modeling.
Results: A total of 1822 patients (monotherapy pool, n=942; JADE COMPARE, n=595; JADE TEEN; n=285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs 12%; week 12), JADE COMPARE (72% and 52% vs 26%; week 16), and JADE TEEN (51% and 60% vs 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations.
Conclusion: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies.

背景：特应性皮炎（atopic dermatitis，AD）患者的皮肤疼痛程度随疾病严重程度升高而加剧，且与显著的生活质量（quality of life，QoL）负担相关。
研究目标：评估阿布昔替尼（abrocitinib）对中重度特应性皮炎成人及青少年患者皮肤疼痛与生活质量的改善效果。
研究方法：本次事后分析纳入的数据来自阿布昔替尼单药治疗（合并2b期[NCT02780167]及3期JADE MONO-1[NCT03349060]、MONO-2[NCT03575871]临床试验）与联合外用治疗（3期JADE COMPARE[NCT03720470]及JADE TEEN[NCT03796676]临床试验）的研究队列。受试者每日一次口服阿布昔替尼200mg、100mg或安慰剂，治疗周期为12或16周（JADE COMPARE试验队列）。皮肤疼痛程度采用特应性皮炎瘙痒与症状评估量表（Pruritus and Symptoms Assessment for Atopic Dermatitis，PSAAD）中的皮肤疼痛数字评分量表（Numerical Rating Scale，NRS）条目进行评估，评估问题为「过去24小时内你的皮肤疼痛程度如何？」，评分范围为0分（无疼痛）至10分（极度疼痛）。同时评估瘙痒症状（采用峰值瘙痒数字评分量表）与生活质量：成人受试者采用皮肤病生活质量指数，青少年受试者采用儿童皮肤病生活质量指数。采用混合效应重复测量模型分析较基线的最小二乘均数（least squares mean，LSM）变化值。
研究结果：本分析共纳入1822例受试者（单药治疗合并队列n=942；JADE COMPARE队列n=595；JADE TEEN队列n=285）。在3个研究队列中，自第2周至第12或16周，阿布昔替尼组患者的PSAAD皮肤疼痛评分较基线的最小二乘均数变化值均显著优于安慰剂组，且疗效呈剂量依赖性。在单药治疗合并队列（第12周）、JADE COMPARE队列（第16周）及JADE TEEN队列（第12周）中，阿布昔替尼200mg、100mg组患者的PSAAD皮肤疼痛评分较基线改善≥4分的比例均显著高于安慰剂组（单药队列：56%、38% vs 12%；JADE COMPARE队列：72%、52% vs 26%；JADE TEEN队列：51%、60% vs 31%）。此外，阿布昔替尼组达到皮肤疼痛改善严格阈值（PSAAD皮肤疼痛评分<2分）的患者比例亦显著高于安慰剂组。与皮肤疼痛改善未达≥4分的受试者相比，皮肤疼痛改善≥4分的成人及青少年患者的生活质量改善更为显著。在3个研究队列中，皮肤疼痛与生活质量、皮肤疼痛与瘙痒症状均呈正相关（相关系数≥0.3）。
研究结论：在所有纳入评估的临床试验中，阿布昔替尼无论是单药治疗还是联合外用治疗，均可改善中重度特应性皮炎成人及青少年患者的皮肤疼痛症状，并伴随生活质量的显著提升。