中度至重度特应性皮炎患者使用瑞莎珠单抗：一项2期随机双盲安慰剂对照研究。
Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study.
作者信息
Tyring Stephen K, Rich Phoebe, Tada Yayoi, Beeck Stefan, Messina Izabella, Liu Jie, Huang Xiaohong, Shumack Stephen
机构信息
Department of Dermatology, McGovern Medical School, University of Texas Health Science Center, 6431 Fannin St, Houston, TX, 77030, USA.
Oregon Health and Science University, Portland, OR, USA.
出版信息
Dermatol Ther (Heidelb). 2023 Feb;13(2):595-608. doi: 10.1007/s13555-022-00876-x. Epub 2023 Jan 2.
INTRODUCTION
Atopic dermatitis (AD) is a heterogeneous disease, with involvement of the T-helper cell (Th) 2, Th22, and potentially Th17 pathways, supporting the use of interleukin (IL)-23 and IL-22 blockade in AD.
METHODS
This phase 2, multicenter, randomized, double-blind, placebo-controlled trial (NCT03706040) evaluated the efficacy and safety of risankizumab, an IL-23 inhibitor, in patients (≥ 12 years old) with moderate-to-severe AD, defined by an Eczema Area and Severity Index (EASI) ≥ 16, affected body surface area ≥ 10%, and a Validated Investigator Global Assessment for AD (vIGA-AD) score ≥ 3. Patients were randomized 2:2:1 to 16-week treatment with risankizumab 150 mg, risankizumab 300 mg, or placebo in period A; patients receiving placebo were re-randomized 1:1 to risankizumab 150 mg or 300 mg and patients receiving risankizumab continued on their randomized dose in 36-week period B. Study drug was administered at baseline and weeks 4, 16, 28, and 40. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction from baseline in EASI (EASI 75) at week 16. Safety was analyzed in all randomized patients who received study medication.
RESULTS
Neither the risankizumab 150 mg (n = 69) nor the 300 mg dose group (n = 69) demonstrated a significantly higher proportion of patients achieving EASI 75 at week 16 compared with the placebo group (n = 34; treatment difference [95% CI] 13.0% [-1.7 to 27.7%; P = 0.084] and 10.0% [-4.6 to 24.6%; P = 0.179], respectively). Most adverse events were mild to moderate in severity; five patients receiving risankizumab reported serious adverse events, including two patients who reported cellulitis.
CONCLUSIONS
Risankizumab was generally well tolerated, with no new safety concerns identified. The study's primary endpoint was not met, with no significant difference in the proportion of patients achieving an EASI 75 response at week 16 with risankizumab 150 mg or 300 mg versus placebo.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03706040.
引言
特应性皮炎（AD）是一种异质性疾病，涉及辅助性T细胞（Th）2、Th22以及可能的Th17途径，这支持了在AD中使用白细胞介素（IL）-23和IL-22阻断剂。
方法
这项2期、多中心、随机、双盲、安慰剂对照试验（NCT03706040）评估了IL-23抑制剂瑞莎珠单抗在中度至重度AD患者（≥12岁）中的疗效和安全性，这些患者的湿疹面积和严重程度指数（EASI）≥16、受累体表面积≥10%且AD的有效研究者整体评估（vIGA-AD）评分≥3。在A期，患者按2:2:1随机分为接受150 mg瑞莎珠单抗、300 mg瑞莎珠单抗或安慰剂治疗16周；接受安慰剂的患者在36周的B期按1:1重新随机分为接受150 mg或300 mg瑞莎珠单抗，接受瑞莎珠单抗的患者继续使用其随机分配的剂量。研究药物在基线、第4周、第16周、第28周和第40周给药。主要终点是在第16周时达到EASI自基线降低≥75%（EASI 75）的患者比例。对所有接受研究药物的随机分组患者进行安全性分析。
结果
与安慰剂组（n = 34）相比，150 mg瑞莎珠单抗组（n = 69）和300 mg剂量组（n = 69）在第16周时达到EASI 75的患者比例均未显著更高（治疗差异[95%CI]分别为13.0%[-1.7至27.7%；P = 0.084]和10.0%[-4.6至24.6%；P = 0.179]）。大多数不良事件的严重程度为轻度至中度；5名接受瑞莎珠单抗治疗的患者报告了严重不良事件，包括2名报告蜂窝织炎的患者。
结论
瑞莎珠单抗总体耐受性良好，未发现新的安全问题。该研究未达到主要终点，150 mg或300 mg瑞莎珠单抗与安慰剂相比，在第16周时达到EASI 75反应的患者比例无显著差异。
试验注册
ClinicalTrials.gov NCT03706040。
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