Department of Dermatology, Oregon Health & Science University, Portland.
Skin for Dermatology, Peterborough, Ontario, Canada.
JAMA Dermatol. 2023 Feb 1;159(2):182-191. doi: 10.1001/jamadermatol.2022.5534.
Lebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials.
To evaluate efficacy and safety of LEB combined with low- to mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD.
DESIGN, SETTING, AND PARTICIPANTS: The ADhere trial was a 16-week randomized, double-blinded, placebo (PBO)-controlled, multicenter, phase 3 clinical trial conducted from February 3, 2020, to September 16, 2021. The study was conducted at 54 outpatient sites across Germany, Poland, Canada, and the US and included adolescent (aged ≥12 to <18 years weighing ≥40 kg) and adult patients with moderate-to-severe AD. The treatment allocation ratio was 2:1 (LEB:PBO).
Overall, 211 patients were randomized to subcutaneous LEB (loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks [Q2W] thereafter) or PBO Q2W in combination with TCS for 16 weeks.
Efficacy analyses at week 16 included proportions of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with 2 or more points improvement from baseline, and 75% improvement in the Eczema Area and Severity Index (EASI-75). Key secondary end points included evaluation of itch, itch interference on sleep, and quality of life. Safety assessments included monitoring adverse events (AEs).
The mean (SD) age of patients was 37.2 (19.3) years, 103 (48.8%) patients were women, 31 (14.7%) patients were Asian, and 28 (13.3%) patients were Black/African American. At week 16, IGA (0,1) was achieved by 145 (41.2%) patients in the LEB+TCS group vs 66 (22.1%) receiving PBO+TCS (P = .01); corresponding proportions of patients achieving EASI-75 were 69.5% vs 42.2% (P < .001). The LEB+TCS group showed statistically significant improvements in all key secondary end points. Most treatment-emergent adverse events (TEAEs) were nonserious, mild or moderate in severity, and did not lead to study discontinuation. The TEAEs frequently reported in the LEB+TCS group included conjunctivitis (7 [4.8%]), headache (7 [4.8%]), hypertension (4 [2.8%]), injection site reactions (4 [2.8%]), and herpes infection (5 [3.4%]) vs 1.5% or less patient-reported frequencies in the PBO+TCS group. Similar frequencies of patient-reported serious AEs following LEB+TCS (n = 2, 1.4%) and PBO+TCS (n = 1, 1.5%).
In this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials.
ClinicalTrials.gov Identifier: NCT04250337.
重要性：靶向白细胞介素 (IL)-13 的高亲和力单克隆抗体 lebrikizumab (LEB) 在 2b 期单药治疗中度至重度特应性皮炎 (AD) 患者的试验中，以及两项 52 周的 3 期临床试验中，展示了疗效和安全性。
目的：评估 LEB 联合低至中效局部皮质类固醇 (TCS) 在中度至重度 AD 患者中的疗效和安全性。
设计、地点和参与者：ADhere 试验是一项 16 周的随机、双盲、安慰剂 (PBO)-对照、多中心、3 期临床试验，于 2020 年 2 月 3 日至 2021 年 9 月 16 日进行。该研究在德国、波兰、加拿大和美国的 54 个门诊点进行，纳入了青少年（年龄≥12 岁至<18 岁，体重≥40 kg）和成年中重度 AD 患者。治疗分配比例为 2:1（LEB:PBO）。
干预措施：共有 211 名患者被随机分配接受皮下 LEB（基线和第 2 周给予 500 mg 负荷剂量，此后每 2 周给予 250 mg [Q2W]）或 PBO Q2W 联合 TCS 治疗 16 周。
主要结果和测量：第 16 周的疗效分析包括 IGA（0,1）[0,1]改善≥2 分且 Eczema Area and Severity Index (EASI-75)改善≥75%的患者比例。关键次要终点包括评估瘙痒、瘙痒对睡眠的干扰和生活质量。安全性评估包括监测不良事件 (AE)。
结果：患者的平均（SD）年龄为 37.2（19.3）岁，103 名（48.8%）患者为女性，31 名（14.7%）患者为亚洲人，28 名（13.3%）患者为黑人/非裔美国人。第 16 周时，LEB+TCS 组有 145 名（41.2%）患者达到 IGA（0,1），而接受 PBO+TCS 的患者为 66 名（22.1%）（P=0.01）；相应达到 EASI-75 的患者比例为 69.5% vs 42.2%（P<0.001）。LEB+TCS 组在所有关键次要终点均显示出统计学显著改善。大多数治疗相关不良事件 (TEAE) 为非严重、轻度或中度，且未导致研究中止。LEB+TCS 组报告的常见 TEAEs 包括结膜炎（7 [4.8%]）、头痛（7 [4.8%]）、高血压（4 [2.8%]）、注射部位反应（4 [2.8%]）和疱疹感染（5 [3.4%]），而 PBO+TCS 组报告的患者频率为 1.5%或更低。LEB+TCS（n=2，1.4%）和 PBO+TCS（n=1，1.5%）组报告的患者严重不良事件 (SAE) 频率相似。
结论和相关性：在这项随机 3 期临床试验中，与 TCS 单药治疗相比，LEB+TCS 可改善中重度 AD 青少年和成年患者的疗效，安全性与之前报道的 AD 试验一致。
试验注册：ClinicalTrials.gov 标识符：NCT04250337。
