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

中文翻译：

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用于治疗中度至重度特应性皮炎的抗 OX40 抗体：一项多中心、双盲、安慰剂对照 2b 期研究

OX40 对于 T 细胞分化和记忆诱导至关重要。抗 OX40 抗体 rocatinlimab 可抑制 OX40 通路。我们评估了 rocatinlimab 对成人中度至重度特应性皮炎的疗效和安全性。这项多中心、双盲、安慰剂对照 2b 期研究是在美国、加拿大、日本和德国的 65 个二级和三级研究中心进行的。符合条件的患者是患有特应性皮炎（美国皮肤病学会共识标准或当地诊断标准）且患有中度至重度疾病活动的成年人（18 岁或以上），根据湿疹面积和严重程度指数 (EASI) 评分定义16 或以上，经过验证的研究者对特应性皮炎的整体评估评分为 3（中度）或 4（重度），并且在筛选和基线时体表面积均为 10% 或更高，并有记录的局部用药反应不足的病史（1 年内）药物治疗或局部治疗在医学上是不可取的。患者被随机分配（1:1:1:1:1），接受每 4 周皮下注射 rocatinlimab（150 mg 或 600 mg）或每 2 周皮下注射（300 mg 或 600 mg），或皮下注射安慰剂直至第 18 周， 18 周积极治疗延长和 20 周随访。根据分组，在第 16 周以及在主动延长和随访期间，将 EASI 评分相对于基线的变化百分比作为主要终点，对所有随机分配的暴露于研究药物的患者进行评估，这些患者在第 16 周或更早时获得基线后 EASI 评分他们被随机分配到。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；根据患者被随机分配到的组对患者进行分析。该研究已在 , 注册。2018年10月22日至2019年10月21日期间，274名患者（114名[42%]名女性，160名[58%]名男性；平均年龄38·0岁[SD 14·5]）被随机分配至其中一种rocatinlimab组（217 [79%] 患者）或安慰剂组（57 [21%] 患者）。与安慰剂 (−15·0 [95% CI −28·6 至 −1·4]) 相比，所有 rocatinlimab 组（每 4 周 150 mg rocatinlimab）在第 16 周观察到 EASI 评分显着降低-48·3 [-62·2 至 -34·0]，p=0·0003；罗卡汀利玛 600 mg 每 4 周 -49·7 [-64·3 至 -35·2]，p=0·0002； rocatinlimab 300 mg 每 2 周 -61·1 [-75·2 至 -47·0]，p<0·0001；和 rocatinlimab 600 mg 每 2 周 -57·4 [-71·3 至 -43·4] ，p<0·0001）。双盲期间接受 rocatinlimab 治疗的患者中最常见的不良事件（不良事件占 rocatinlimab 组总患者的 5% 以上，比安慰剂组更常见）是发热（36 [17%] 名患者）、鼻咽炎（30 [14%] 患者）、寒战（24 [11%] 患者）、头痛（19 [9%] 患者）、口疮性溃疡（15 [7%] 患者）和恶心（13 [6%] 患者）。没有死亡。使用 rocatinlimab 治疗的患者特应性皮炎得到了逐步改善，大多数患者在治疗停止后仍维持这种状态。治疗耐受性良好。协和麒麟.