近日，美国西奈山伊坎医学院Emma Guttman-Yassky团队研究了罗卡替尼单抗治疗中重度特应性皮炎的疗效和安全性。相关论文于2025年11月24日发表在《柳叶刀》杂志上。

罗卡替尼是一种T细胞再平衡疗法，通过靶向活化T细胞表面表达的OX40受体来抑制和减少致病性T细胞的数量。研究组进行了两项全球3期研究，以评估罗卡替尼治疗成人中度至重度特应性皮炎的有效性和安全性。

ROCKET-IGNITE（IGNITE）与ROCKET-HORIZON（HORIZON）是两项分别在19个国家开展的、为期24周的随机双盲安慰剂对照Ⅲ期临床试验。合格受试者需为年满18周岁、经美国皮肤病学会共识标准确诊至少1年、且患有中度至重度特应性皮炎的患者，其疾病活动度需符合以下标准：湿疹面积与严重程度指数（EASI）评分≥16分，特应性皮炎研究者整体评估量表（vIGA-AD）评分达3分（中度）或4分（重度），体表受累面积≥10%。在IGNITE研究中，患者按3:2:2比例随机分配至皮下注射300mg罗卡替尼、150mg罗卡替尼或安慰剂组；HORIZON研究则按3:1比例随机分配至300mg罗卡替尼组或安慰剂组。随机分组按基线疾病严重程度（vIGA-AD评分3分vs4分）和地理区域（日本vs非日本亚洲国家vs其他地区）进行分层。两项试验的治疗方案均为24周，在第0、2、4周给药后改为每4周给药一次，末次给药为第20周。两项试验的双重主要终点均为第24周时EASI-75应答率（EASI评分较基线改善≥75%）及vIGA-AD评分达到0或1分（即0分[皮损完全清除]或1分[几乎完全清除]，且较基线改善≥2分）。自第1天起允许使用救援治疗（包括局部治疗、光疗和系统治疗），所有接受救援治疗的患者自首次使用后均被视为无应答者，但通常可继续接受研究治疗方案（除非方案禁止）。疗效分析在所有随机化患者中进行；安全性分析则覆盖所有接受至少一剂研究治疗的患者，并按实际治疗方案分组。试验已在ClinicalTrials.gov注册：ROCKET-IGNITE（NCT05398445）和ROCKET-HORIZON（NCT05651711）。

2022年5月31日至2024年6月12日期间，IGNITE研究共随机入组769例患者（其中2例在研究方案重置前按早期方案入组，被排除在分析之外；方案更新后，300 mg罗卡替尼组纳入328例，150 mg罗卡替尼组纳入217例，安慰剂组纳入222例）。2022年12月14日至2023年12月12日期间，HORIZON研究共随机入组726例患者（300 mg罗卡替尼组543例，安慰剂组183例）。两项试验均达到共同主要终点。在IGNITE研究中，第24周时罗卡替尼组EASI-75应答率较安慰剂组显著改善（300 mg罗卡替尼组326例患者中138例[42%]；150 mg组215例中78例[36%]；安慰剂组219例中28例[13%]；与安慰剂组百分比差：300 mg组29.5%[95%CI 22.3-36.1]，p<0.001；150 mg组23.4%[15.4-30.9]，p<0.001）。HORIZON研究中同样观察到显著改善（罗卡替尼组543例中178例[33%] vs 安慰剂组183例中25例[14%]；百分比差19.1%[12.4-25.2]，p<0.001）。

第24周时vIGA-AD评分达到0或1的应答率在IGNITE研究中亦显著优于安慰剂（300 mg组326例中77例[24%]；150 mg组215例中41例[19%]；安慰剂组219例中19例[9%]；与安慰剂组百分比差：300 mg组14.9%[8.8-20.6]，p<0.001；150 mg组10.3%[3.8-16.6]，p=0.002）。HORIZON研究中该指标同样显著改善（300 mg组543例中105例[19%] vs 安慰剂组183例中12例[7%]；百分比差12.8%[7.6-17.3]，p<0.001）。两项研究中罗卡替尼组与安慰剂组治疗期间不良事件发生率总体相似。罗卡替尼组最常见不良事件（定义为任意罗卡替尼组发生率≥4%且≥安慰剂组2倍）包括发热（300 mg组870例中105例[12%]；150 mg组214例中26例[12%]）、寒战（300 mg组870例中48例[6%]；150 mg组214例中5例[2%]）和口腔溃疡（300 mg组870例中38例[4%]；150 mg组214例中6例[3%]）。多数发热与寒战被判定为注射相关反应，严重程度多为轻中度，且主要发生于首次给药后。罗卡替尼组严重不良事件发生率为2%-5%，安慰剂组为4%-6%。无死亡病例报告。

研究结果表明，与安慰剂相比，罗卡替尼治疗在临床终点（包括EASI-75反应的主要终点和vIGA-AD评分为0或1）上取得了具有统计学意义和临床意义的改善，并且在中度至重度特应性皮炎成人患者中具有临床可接受的安全性。

附：英文原文

Title: Efficacy and safety of rocatinlimab for the treatment of moderate-to-severe atopic dermatitis in ROCKET-IGNITE and ROCKET-HORIZON: two global, double-blind, placebo-controlled, randomised phase 3 clinical trials

Author: Emma Guttman-Yassky, Kenji Kabashima, Margitta Worm, Paula C Luna, H Chih-Ho Hong, Raj Chovatiya, Jonathan A Bernstein, Johannes S Kern, Benjamin D Ehst, Nina Magnolo, Pedro Herranz-Pinto, Linda Stein Gold, Howard Sofen, Andrew E Pink, Ehsanollah Esfandiari, Takahiro Arai, Yiping Yang, Rebecca Shi, Carolina Barragan, Greg Kricorian, Liat Schwartz-Sagi, Robert Bissonnette

Issue&Volume: 2025-11-24

Abstract:

Background

Rocatinlimab is a T cell rebalancing therapy that inhibits and reduces the number of pathogenic T cells by targeting the OX40 receptor expressed on the surface of activated T cells. Two global phase 3 studies were performed to assess the efficacy and safety of rocatinlimab for the treatment of moderate-to-severe atopic dermatitis in adults.

Methods

ROCKET-IGNITE (IGNITE) and ROCKET-HORIZON (HORIZON) were 24-week randomised, double-blind, placebo-controlled phase 3 trials conducted in 19 countries each. Eligible patients were 18 years and older with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria) diagnosed 1 year or longer before study entry with moderate-to-severe disease activity, defined by an Eczema Area and Severity Index (EASI) score of 16 and over, validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 (moderate) or 4 (severe), and affected body surface area of 10% and above. In IGNITE, patients were randomly allocated in a 3:2:2 ratio to receive subcutaneous 300 mg rocatinlimab, 150 mg rocatinlimab, or placebo; in HORIZON, patients were randomised 3:1 to receive subcutaneous 300 mg rocatinlimab or placebo. Randomisation was stratified by baseline disease severity (vIGA-AD score of 3 vs 4) and geographical region (Japan vs non-Japan Asian countries vs rest of world). Across both trials, 24-week treatment was administered at weeks 0, 2, and 4 and then every 4 weeks thereafter with the last dose at week 20. The coprimary endpoints for both trials were EASI-75 response (≥75% improvement in EASI score from baseline) at week 24 and vIGA-AD score of 0 or 1 (defined as a score of 0 [clear skin] or 1 [almost clear skin], representing a ≥2-point improvement from baseline) at week 24. Rescue therapy use, including topical therapy, phototherapy, and systemic therapy, was permitted from day 1; all patients who received rescue therapy were considered non-responders for all visits after the first use of rescue therapy but could generally continue study treatment unless prohibited per protocol. Efficacy analyses were conducted in all randomised patients; safety analyses were conducted in all patients who received one or more dose of study treatment, with patients grouped according to actual treatment received. The trials were registered at ClinicalTrials.gov: ROCKET-IGNITE (NCT05398445) and ROCKET-HORIZON (NCT05651711).

Findings

Between May 31, 2022, and June 12, 2024, 769 patients were randomised in IGNITE (two patients were enrolled under an earlier protocol before study re-design and excluded from the analysis; after the protocol update, 328 were included in the 300 mg rocatinlimab group; 217 in the 150 mg rocatinlimab group; and 222 in the placebo group) and between Dec 14, 2022, and Dec 12, 2023, 726 patients were randomised in HORIZON (543 in 300 mg rocatinlimab and 183 in placebo). Both trials met their coprimary endpoints. Rocatinlimab treatment resulted in statistically significant improvements in EASI-75 response in comparison with placebo at week 24 in IGNITE (138 [42%] of 326 patients on 300 mg rocatinlimab; 78 [36%] of 215 on 150 mg rocatinlimab; and 28 [13%] of 219 on placebo; percentage difference vs placebo: 300 mg rocatinlimab 29·5% [95% CI 22·3–36·1], p<0·001 and 150 mg rocatinlimab 23·4% [15·4–30·9], p<0·001) and HORIZON (rocatinlimab, 178 [33%] of 543 vs placebo, 25 [14%] of 183; percentage difference 19·1% [95% CI 12·4–25·2], p<0·001). Statistically significant improvements with rocatinlimab treatment in comparison with placebo were also observed at week 24 for vIGA-AD score of 0 or 1 response in IGNITE (77 [24%] of 326 patients on300 mg rocatinlimab; 41 [19%] of 215 patients on 150 mg rocatinlimab; and 19 [9%] of 219 patients on placebo; percentage difference vs placebo 14·9% [95% CI 8·8–20·6], p<0·001 for 300 mg rocatinlimab and 10·3% [3·8–16·6], p=0·002 for 150 mg rocatinlimab) and HORIZON (105 [19%] of 543 for 300 mg rocatinlimab vs 12 [7%] of 183 for placebo; percentage difference 12·8% [95% CI 7·6–17·3], p<0·001). The incidences of treatment-emergent adverse events were generally similar across rocatinlimab and placebo treatment groups in IGNITE and HORIZON. The most frequently reported adverse events in patients receiving rocatinlimab (defined as occurring in ≥4% of patients in any rocatinlimab treatment group and at a rate ≥2 times that of placebo) included pyrexia (105 [12%] of 870 for 300 mg rocatinlimab and 26 [12%] of 214 for 150 mg rocatinlimab), chills (48 [6%] of 870 and five [2%] of 214 for the 300 mg and 150 mg doses, respectively), and aphthous ulcers (38 [4%] of 870 and six [3%] of 214, respectively). Most events of pyrexia and chills were considered injection-related reactions; events were generally mild or moderate in severity and primarily occurred after the first dose. Serious adverse events were reported in 2% to 5% of patients in the rocatinlimab groups and 4% to 6% of patients in the placebo groups. No deaths were reported.

Interpretation

Rocatinlimab treatment resulted in statistically significant and clinically meaningful improvements across clinical endpoints, including the coprimary endpoints of EASI-75 response and vIGA-AD score of 0 or 1, in comparison with placebo and had a clinically acceptable safety profile in adult patients with moderate-to-severe atopic dermatitis.

DOI: 10.1016/S0140-6736(25)01865-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01865-3/abstract