基于既往用药史的芦可利替尼乳膏治疗特应性皮炎的有效性和安全性

IF 3.5 3区医学 Q1 DERMATOLOGY Dermatology and Therapy Pub Date : 2024-11-01 Epub Date: 2024-10-07 DOI:10.1007/s13555-024-01272-3

Andrew Blauvelt, Howard Kallender, Daniel Sturm, Qian Li, Haobo Ren, Lawrence F Eichenfield

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引用次数: 0

摘要

简介：对于一些特应性皮炎（AD）患者来说，外用皮质类固醇激素（TCS）、外用钙神经蛋白抑制剂（TCI）和全身疗法都不足以控制病情，或与不良反应（AEs）相关。在两项关键性三期研究（TRuE-AD1/TRuE-AD2）中，Ruxolitinib乳膏单药疗法在入组患者中显示出抗炎和抗瘙痒效果；在44周的长期安全性（LTS）期间，大多数患者都能根据需要长期控制病情。这项事后分析探讨了1.5%芦可利替尼乳膏的疗效和安全性，并根据之前的用药情况进行了分析：年龄≥12岁的TRuE-AD1/TRuE-AD2入组患者按2:2:1随机分配至每日两次的0.75%或1.5%的鲁索利替尼乳膏或载体乳膏，为期8周，然后进行为期44周的长期安全期；最初使用载体的患者按1:1重新随机分配至任一鲁索利替尼乳膏强度：在入组 12 个月内（N = 1249），89.4% 的有疗效的患者使用了载体或 Ruxolitinib 乳膏（n = 725）；其中 80.4% 接受了 TCS（n = 583），22.2% 接受了 TCI（n = 161），20.3% 接受了 TCS + TCI（n = 147），18.9% 接受了全身治疗（n = 137）。在之前的用药亚组中，使用鲁索利替尼乳膏的患者在第8周时达到研究者总体评估（IGA）-治疗成功（IGA 0/1，与基线相比改善≥2级）、湿疹面积和严重程度指数与基线相比改善≥75%、瘙痒数字评分量表评分与基线相比改善≥4分的结果没有实质性差异。研究结果与总体研究人群的结果相似。在长效治疗期间的所有研究访视中，每个亚组中都有超过70%的患者IGA为0/1，且比例较低（一般为1%）：持续使用鲁索利替尼乳膏单药治疗8周后再按需使用，无论之前是否接受过局部或全身治疗，均有效且耐受性良好，结果与总体研究人群的结果相似：试验注册：ClinicalTrials.gov Identifier，NCT03745638/NCT03745651。

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Efficacy and Safety of Ruxolitinib Cream in Atopic Dermatitis Based on Previous Medication History.

Introduction: For some patients with atopic dermatitis (AD), topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and systemic therapies are inadequate to control disease or are associated with adverse events (AEs). Ruxolitinib cream monotherapy demonstrated anti-inflammatory and anti-pruritic effects among patients enrolled in two pivotal phase 3 studies (TRuE-AD1/TRuE-AD2); most patients had long-term disease control with as-needed use during the 44-week long-term safety (LTS) period. This post hoc analysis explored efficacy and safety of 1.5% ruxolitinib cream by previous medication use.

Methods: Patients aged ≥ 12 years enrolled in TRuE-AD1/TRuE-AD2 were randomized 2:2:1 to twice-daily 0.75% or 1.5% ruxolitinib cream or vehicle cream for 8 weeks, followed by a 44-week LTS period; patients initially on vehicle were re-randomized 1:1 to either ruxolitinib cream strength.

Results: Within 12 months of enrollment (N = 1249), previous AD therapies were used by 89.4% of efficacy-evaluable patients applying vehicle or ruxolitinib cream (n = 725); of these, 80.4% received TCS (n = 583), 22.2% TCI (n = 161), 20.3% TCS + TCI (n = 147), and 18.9% systemic therapies (n = 137). Across previous medication subgroups, achievement of Investigator's Global Assessment (IGA)-treatment success (IGA 0/1 with ≥ 2-grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index from baseline, and ≥ 4-point improvement in Itch numerical rating scale score from baseline at Week 8 did not substantially differ among patients who applied ruxolitinib cream. Outcomes were similar to those in the overall study population. At all study visits during the LTS period, > 70% of patients in each subgroup had IGA 0/1 and a low percentage (generally < 3%) of affected body surface area. Treatment-related AEs across subgroups were reported in 7.3% (n = 35/481) to 17.4% (n = 19/109) of patients.

Conclusions: Continuous-use ruxolitinib cream monotherapy for 8 weeks followed by as-needed use was effective and well tolerated, regardless of previous topical or systemic therapy, with outcomes similar to those achieved in the overall study population.

Trial registration: ClinicalTrials.gov Identifier, NCT03745638/NCT03745651.

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来源期刊

Dermatology and Therapy Medicine-Dermatology

CiteScore

6.00

自引率

8.80%

发文量

187

审稿时长

6 weeks

期刊介绍： Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.