Comparison of Long-Term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis Between Dupilumab-Exposed and Dupilumab-Naïve Patients

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY Clinical Drug Investigation Pub Date : 2023-12-17 DOI:10.1007/s40261-023-01336-w

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Abstract

Background and Objectives

Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients \(\ge\) 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients.

Methods

A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit.

Results

A total of 113 patients (72 males, 63.7%; mean age: 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively.

Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (p < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52.

Conclusions

This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.

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乌达帕替尼治疗特应性皮炎的长期有效性和安全性在杜匹单抗暴露患者和杜匹单抗无效患者之间的比较

摘要背景和目的 Upadacitinib是一种口服选择性Janus激酶-1抑制剂，已被批准用于治疗12岁患者的中重度特应性皮炎（AD）。在现实生活中，达帕替尼目前是治疗现有系统疗法失败患者的有效选择，尤其是因缺乏疗效或出现不良反应而停用杜匹单抗的患者。本研究的目的是比较达帕替尼对曾接受过杜比单抗治疗失败的 AD 患者和生物制剂新药患者的有效性和安全性。方法在意大利四个皮肤病转诊中心（米兰、佩鲁贾、那不勒斯和维琴察）开展了一项回顾性、多中心、观察性、真实生活研究。基线特征包括年龄、性别、注意力缺失症病史和严重程度、既往治疗情况、合并症和并发症。使用湿疹面积严重性指数（EASI）、皮肤科生活质量指数（DLQI）和瘙痒数字评定量表（P-NRS）评分评估基线和第4周（W4）、W16、W24和W52周的AD严重程度。在基线和每次随访时对全血细胞计数、肝肾功能、血脂组合和肌肉酶[乳酸脱氢酶（LDH）和肌酸磷酸激酶（CPK）]进行评估。结果共有113名患者（72名男性，63.7%；平均年龄：37.22 ± 16.8岁）被纳入分析，所有患者均接受治疗并随访至W16，91名患者（80.5%）和75名患者（66.4%）分别接受治疗并随访至W24和W52。在 W16、W24 和 W52 期，EASI 平均得分分别从 24.30 ± 10.27 显著降至 1.28 ± 4.34、0.74 ± 2.31 和 0.25 ± 1.34（p < 0.0001）。具体而言，在 W16，达到 EASI-75、EASI-90 和 EASI-100 的患者比例分别为 85.21%、76.35% 和 66.11%。在 W24 期，分别有 88.54%、85.42% 和 78.37% 的患者达到了 EASI-75、EASI-90 和 EASI-100。最后，在 W52 时，90.1% 的患者达到 EASI-75，88.3% 的患者达到 EASI-90，83.0% 的患者达到 EASI-100。结论本研究证实了达达替尼治疗中重度AD成人患者的临床疗效，这些患者曾因疗效不佳或不良事件而停用杜比鲁单抗，而且是生物制剂的天真者；因此，既往的治疗似乎并不影响达达替尼治疗的反应。

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来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.