美国乔治华盛顿大学Jonathan I. Silverberg团队研究了来瑞组单抗治疗中重度特应性皮炎的疗效与安全性。2023年3月15日出版的《新英格兰医学杂志》发表了这项成果。

来瑞组单抗是一种靶向白细胞介素13的高亲和力IgG4单克隆抗体，可防止白细胞介素4Rα–白细胞介素13Rα1异二聚体受体信号复合物的形成。

研究组进行了两项设计相同、为期52周的随机、双盲、安慰剂对照的3期临床试验；两项试验都包括16周的诱导期和36周的维持期。符合条件的中度至重度特应性皮炎患者（成人[≥18岁]和青少年[12至<18岁，体重≥40kg]）以2：1的比例被随机分配接受剂量为250 mg的来瑞组单抗（基线和第2周的负荷剂量为500mg）或安慰剂治疗，每2周皮下给药一次。

对诱导期结果进行了长达16周的评估，并包含在本报告中。主要结局是研究者的全球评估（IGA）评分为0或1（表示皮肤病变清除或几乎清除；范围为0至4[严重疾病]），在第16周时比基线降低（表示改善）至少2分。次要结局包括湿疹面积和严重程度指数评分（EASI-75缓解）改善75%，瘙痒，以及瘙痒对睡眠干扰的评估。还对安全性进行了评估。

在试验1中，来瑞组单抗组283名患者中有43.1%达到主要结局，安慰剂组141名患者中有12.7%；两组EASI-75缓解发生率分别为58.8%和16.2%，组间差异均显著。在试验2中，来瑞组单抗组281名患者中有33.2%达到主要结局，安慰剂组146名患者中有10.8%；两组EASI-75缓解发生率分别为52.1%和18.1%，组间差异均显著。对瘙痒和瘙痒对睡眠干扰的测量表明，来瑞组单抗治疗效果有所改善。接受来瑞组单抗治疗的患者结膜炎发病率高于接受安慰剂治疗的患者。诱导期内大多数不良事件的严重程度为轻度或中度，不会导致试验中止。

研究结果表明，在两项3期试验的诱导期内，16周的来瑞组单抗治疗对患有中度至重度特应性皮炎的青少年和成人有效。

附：英文原文

Title: Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis

Author: Jonathan I. Silverberg, M.D., Ph.D., M.P.H,, Emma Guttman-Yassky, M.D., Ph.D.,, Diamant Thai, M.D.,, Alan D. Irvine, M.D.,, Linda Stein Gold, M.D.,, Andrew Blauvelt, M.D.,, Eric L. Simpson, M.D.,, Chia-Yu Chu, M.D., Ph.D.,, Zhuqing Liu, Ph.D.,, Renata Gontijo Lima, M.D.,, Sreekumar G. Pillai, Ph.D.,, and Julien Seneschal, M.D., Ph.D.

Issue&Volume: 2023-03-15

Abstract:

Background

Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα–interleukin-13Rα1 heterodimer receptor signaling complex.

Methods

We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator’s Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed.

Results

In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation.

Conclusions

In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis.

DOI: 10.1056/NEJMoa2206714

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2206714