美国西奈山伊坎医学院Emma Guttman-Yassky团队研究了抗OX40抗体治疗中重度特应性皮炎的疗效与安全性。相关论文于2022年12月9日发表在《柳叶刀》杂志上。

OX40对T细胞分化和记忆诱导至关重要。抗OX40抗体rocatinlimab可抑制OX40途径。研究组评估了rocatinlimab在成人中重度特应性皮炎中的疗效和安全性。

这项多中心、双盲、安慰剂对照的2b期临床研究在美国、加拿大、日本和德国的65个二级和三级研究机构进行。符合条件的患者为成年人（18岁或以上），患有经证实的特应性皮炎（美国皮肤病学会共识标准或当地诊断标准），具有中度至重度疾病活动，如湿疹面积和严重程度指数（EASI）评分为16或以上，经验证的研究者特应性皮肤炎全球评估评分为3（中度）或4（重度），在筛查和基线时受影响的体表面积为10%或更高，有记录在案的病史（1年内）对局部药物反应不充分或局部治疗在医学上不可取。

患者被随机分配（1:1:1:1:1），每4周（150 mg或600 mg）或每2周（300 mg或600 g）接受一次皮下rocatinlimab或安慰剂治疗，直至第18周，18周主动治疗延长，在20周时随访。根据随机分配的各组，在第16周、主动延长和随访期间，所有随机分配的患者在第16周或更早时暴露于研究药物，EASI评分与基线相比的百分比变化被评估为主要终点。对所有随机分配的暴露于研究药物的患者进行安全性评估；根据随机分组对患者进行分析。

2018年10月22日至2019年10月21日，274名患者（114[42%]名女性，160[58%]名男性；平均年龄38.0岁）被随机分配到rocatinlimab组（217[79%]名患者）或安慰剂组（57[21%]名患者）。与安慰剂组相比（-15.0），在第16周时，所有rocatinlimab组的EASI评分均显著降低，其中每4周150 mg组−48.3；每4周600 mg组−49.7；每2周300 mg组−61.1；每2周600 mg组−57.4。

在双盲期间，接受rocatinlimab治疗的患者中最常见的不良事件（不良事件数超过rocatinlimab组5%的患者，且比安慰剂组更常见）有发热（36例[17%]患者）、鼻咽炎（30例[14%]患者）、寒战（24例[11%]患者）、头痛（19例[9%]患者）、阿弗他溃疡（15例[7%]患者）和恶心（13例[6%]患者）。没有患者死亡。

研究结果表明，Rocatinlimab治疗特应性皮炎患者有进展性改善，大多数患者在停药后仍保持这种改善，且治疗耐受性良好。

附：英文原文

Title: An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study

Author: Emma Guttman-Yassky, Eric L Simpson, Kristian Reich, Kenji Kabashima, Ken Igawa, Tetsuya Suzuki, Hirotaka Mano, Takeshi Matsui, Ehsanollah Esfandiari, Masutaka Furue

Issue&Volume: 2022-12-09

Abstract:

Background

OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with moderate-to-severe atopic dermatitis.

Methods

This multicentre, double-blind, placebo-controlled phase 2b study was done at 65 secondary and tertiary sites in the USA, Canada, Japan, and Germany. Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria or local diagnostic criteria) with moderate-to-severe disease activity, as defined by an Eczema Area and Severity Index (EASI) score of 16 or more, validated Investigator's Global Assessment for Atopic Dermatitis score of 3 (moderate) or 4 (severe), and affected body surface area 10% or higher at both screening and baseline, with documented history (within 1 year) of inadequate response to topical medications or if topical treatments were medically inadvisable. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous rocatinlimab every 4 weeks (150 mg or 600 mg) or every 2 weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. Percentage change from baseline in EASI score was assessed as the primary endpoint at week 16 and during the active extension and follow-up in all randomly assigned patients exposed to study drug with a post-baseline EASI score at week 16 or earlier according to the group they were randomly assigned to. Safety was assessed in all randomly assigned patients exposed to study drug; patients were analysed according to the group they were randomly assigned to. The study is registered with ClinicalTrials.gov, NCT03703102.

Findings

Between Oct 22, 2018, and Oct 21, 2019, 274 patients (114 [42%] women, 160 [58%] men; mean age 38·0 years [SD 14·5]) were randomly assigned to one of the rocatinlimab groups (217 [79%] patients) or to the placebo group (57 [21%] patients). Compared with placebo (15·0 [95% CI 28·6 to 1·4]), significant least-squares mean percent reductions in EASI score at week 16 were observed in all rocatinlimab groups (rocatinlimab 150 mg every 4 weeks 48·3 [62·2 to 34·0], p=0·0003; rocatinlimab 600 mg every 4 weeks 49·7 [64·3 to 35·2], p=0·0002; rocatinlimab 300 mg every 2 weeks 61·1 [75·2 to 47·0], p<0·0001; and rocatinlimab 600 mg every 2 weeks 57·4 [71·3 to 43·4], p<0·0001). The most common adverse events during the double-blind period in patients receiving rocatinlimab (adverse events ≥5% of patients in the total rocatinlimab group and more common than the placebo group) were pyrexia (36 [17%] patients), nasopharyngitis (30 [14%] patients), chills (24 [11%] patients), headache (19 [9%] patients), aphthous ulcer (15 [7%] patients), and nausea (13 [6%] patients). There were no deaths.

Interpretation

Patients treated with rocatinlimab had progressive improvements in atopic dermatitis, which was maintained in most patients after treatment discontinuation. Treatment was well tolerated.

DOI: 10.1016/S0140-6736(22)02037-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02037-2/fulltext