Two-Year Efficacy and Safety of Lebrikizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Long-Term Extension (ADjoin).

IF 3.5 3区医学 Q1 DERMATOLOGY

Dermatology and Therapy Pub Date : 2025-08-01 Epub Date: 2025-06-23 DOI:10.1007/s13555-025-01452-9

Emma Guttman-Yassky, Stephan Weidinger, Eric L Simpson, Melinda Gooderham, Alan D Irvine, Lynda Spelman, Jonathan I Silverberg, Hany ElMaraghy, Louise DeLuca-Carter, Maria Lucia Buziqui Piruzeli, Chaoran Hu, Fan Emily Yang, Evangeline Pierce, Laia Bardolet, Diamant Thaçi

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引用次数: 0

Abstract

Introduction: The efficacy and safety of lebrikizumab, a high-affinity monoclonal antibody targeting interleukin-13, were investigated in patients with moderate-to-severe atopic dermatitis (AD) up to 52 weeks in phase 3 trials. This analysis evaluates safety and maintenance of response through 104 weeks of lebrikizumab treatment in patients with moderate-to-severe AD who achieved clinical response with lebrikizumab at week 16.

Methods: ADjoin is a 100-week phase 3 long-term extension study. Adult and adolescent patients with moderate-to-severe AD were enrolled into parent studies ADvocate1, ADvocate2, and ADhere. ADvocate1&2 week 16 lebrikizumab clinical responders (patients who achieved Investigator's Global Assessment [IGA] [0, 1] or Eczema Area and Severity Index [EASI] 75 without rescue) were re-randomized 2:2:1 to lebrikizumab 250 mg Q2W, Q4W, or placebo (lebrikizumab withdrawal). Patients who completed week 52 of ADvocate1&2 could enroll into ADjoin. ADhere week 16 lebrikizumab clinical responders could enroll into ADjoin and were randomized 2:1 to lebrikizumab 250 mg Q2W or Q4W. Analyses were performed on patients who received 104 weeks of lebrikizumab treatment in parent and extension studies combined. Efficacy analyses are reported as observed from week 16 for patients who were re-randomized to lebrikizumab Q2W or Q4W. Safety assessments included monitoring adverse events.

Results: IGA (0, 1) was maintained by 86.4% (Q2W) and 76.4% (Q4W) patients from ADvocate1&2 and 83.9% (Q2W) and 78.6% (Q4W) patients from ADhere at week 104. EASI 75 was maintained by 95.6% (Q2W) and 96.3% (Q4W) ADvocate1&2 patients and 95.1% (Q2W) and 96.0% (Q4W) ADhere patients at week 104. Pruritus NRS ≥ 4-point improvement was maintained by 100% (Q2W) and 89.7% (Q4W) ADvocate1&2 patients at week 104 and 81.8% (Q2W) and 90.0% (Q4W) ADhere patients at week 68. During ADjoin, adverse events were reported by 62.2% of patients from ADvocate1&2 and ADhere who received lebrikizumab Q2W or Q4W, with the majority being mild (31.5%) or moderate (27.0%) in severity, and 2.2% leading to discontinuation due to adverse event.

Conclusions: Skin and itch outcomes were maintained over 2 years of continuous lebrikizumab 250 mg treatment. The safety profile of lebrikizumab in ADjoin is consistent with previous lebrikizumab studies in patients with moderate-to-severe AD.

Trial registration: ClinicalTrials.gov, NCT04392154.

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Lebrikizumab在中重度特应性皮炎患者中的两年疗效和安全性：长期扩展（ADjoin）。

lebrikizumab是一种靶向白介素-13的高亲和力单克隆抗体，在中重度特应性皮炎（AD）患者长达52周的3期试验中研究了其疗效和安全性。该分析评估了中度至重度AD患者在第16周获得临床反应的lebrikizumab治疗104周的安全性和维持反应。方法：ADjoin是一项为期100周的3期长期扩展研究。成人和青少年中度至重度AD患者被纳入家长研究ADvocate1、ADvocate2和粘附。advocate1和2周16 lebrikizumab临床应答者（达到研究者总体评估[IGA][0,1]或湿疹面积和严重程度指数[EASI] 75且无救援的患者）以2:2:1重新随机分配到lebrikizumab 250 mg Q2W， Q4W或安慰剂（lebrikizumab停药）。完成第52周advocate1和2治疗的患者可以加入ADjoin。坚持第16周，lebrikizumab临床应答者可以入组ADjoin，并按2:1随机分配至lebrikizumab 250mg Q2W或Q4W。对在亲本研究和扩展研究中接受104周lebrikizumab治疗的患者进行了分析。从第16周开始，对重新随机分配到lebrikizumab Q2W或Q4W的患者进行疗效分析。安全性评估包括监测不良事件。结果：在第104周时，来自advocate1和2的患者中有86.4% （Q2W）和76.4% （Q4W）维持IGA(0,1)，来自粘附的患者中有83.9% （Q2W）和78.6% （Q4W）维持IGA（0,1）。第104周时，EASI 75维持率分别为95.6% （Q2W）和96.3% （Q4W）的advocate1和2患者以及95.1% （Q2W）和96.0% （Q4W）的依从患者。104周时，100% （Q2W）和89.7% （Q4W）的advocate1和2患者，以及68周时，81.8% （Q2W）和90.0% （Q4W）的依从患者的瘙痒症状NRS≥4点改善维持。在ADjoin期间，62.2%的ADvocate1&2和依从组患者在接受来布单抗Q2W或Q4W治疗时报告了不良事件，其中大多数严重程度为轻度（31.5%）或中度（27.0%），2.2%因不良事件导致停药。结论：持续使用lebrikizumab 250mg治疗可维持2年以上的皮肤和瘙痒结果。lebrikizumab在ADjoin中的安全性与先前lebrikizumab在中重度AD患者中的研究一致。试验注册：ClinicalTrials.gov, NCT04392154。

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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.