巴瑞替尼2mg治疗特应性皮炎的临床个体化：基线体表面积和快速起效可预测第16周的疗效
Clinical Tailoring of Baricitinib 2 mg in Atopic Dermatitis: Baseline Body Surface Area and Rapid Onset of Action Identifies Response at Week 16.
作者信息
Silverberg Jonathan I, Boguniewicz Mark, Waibel Jill, Weisman Jamie, Strowd Lindsay, Sun Luna, Ding Yuxin, Feely Meghan, Nunes Fabio P, Simpson Eric L
机构信息
Department of Dermatology, George Washington University School of Medicine, Washington, DC, USA.
Division of Allergy-Immunology, Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, CO, USA.
出版信息
Dermatol Ther (Heidelb). 2022 Jan;12(1):137-148. doi: 10.1007/s13555-021-00640-7. Epub 2021 Nov 30.
INTRODUCTION
Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5.
METHODS
Classification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder.
RESULTS
At week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10-50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints.
CONCLUSION
Baseline BSA of 10-50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy.
CLINICAL TRIAL REGISTRATION
NCT03435081.
简介
巴瑞替尼是一种口服的Janus激酶（JAK）1/JAK2抑制剂，在欧盟和日本被批准用于对全身治疗有需求的成人中重度特应性皮炎（AD）的治疗。在正在进行的、安慰剂对照的3期试验BREEZE-AD5中，每日一次口服2mg巴瑞替尼单药治疗改善了对局部皮质类固醇反应不足或不耐受的中重度AD患者的病情。这项事后分析旨在通过一种基于基线体表面积（BSA）受累情况和早期临床改善情况的拟议临床定制方法，在BREEZE-AD5中识别对2mg巴瑞替尼有反应的患者。
方法
采用分类回归树方法评估在接受2mg巴瑞替尼治疗患者中，第16周达到湿疹面积和严重程度指数改善≥75%（EASI75）的患者比例的基线预测因素。二乘二列联表评估早期反应（定义为第4周或第8周时BSA改善≥50%或瘙痒数字评定量表较基线改善≥3分）与第16周反应之间的关联，分别针对达到EASI75的患者比例、验证的AD研究者整体评估（vIGA-AD）评分为0或1，或瘙痒改善≥4分（瘙痒≥4）的情况。缺失数据被视为无反应者。
结果
在第16周时，基线BSA为10%-50%的接受2mg巴瑞替尼治疗的患者中，37.5%和31.7%达到了EASI75和vIGA-AD（0,1），而BSA>50%的患者中这一比例分别为9.5%和4.8%。第4周时皮肤炎症或瘙痒的早期反应与第16周时相应的EASI75、vIGA-AD（0,1）以及瘙痒≥4的比例分别为55.4%、48.2%和39.3%相关，而第8周时的早期反应与达到这些终点的患者比例分别为66.7%、56.1%和42.1%相关。
结论
基线BSA为10%-50%以及2mg巴瑞替尼治疗4周或8周后的早期临床改善可能识别出最有可能从长期2mg巴瑞替尼治疗中获益的患者。临床试验注册编号：NCT03435081。
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