Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis
Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis
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DOI：
10.1056/nejmoa1806382
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发表时间：
2018-10-04
影响因子：
158.5
通讯作者：
Banerjee, Subhashis
中科院分区：
文献类型：
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作者：
Papp, Kim;Gordon, Kenneth;Banerjee, Subhashis
酪氨酸激酶2（TYK 2）信号通路介导细胞因子信号传导，与银屑病的病理生理学有关。TYK 2的选择性抑制剂可能是有效的治疗psorias.METHODSWe进行了2期，双盲试验的TYK 2抑制剂，BMS-986165，在成人中度至重度银屑病，排除患者以前缺乏反应的药物靶向细胞因子信号通过相同的酪氨酸激酶途径。患者被随机分配接受口服药物，剂量为每隔一天3 mg，每日3 mg，每日2次3 mg，每日2次6 mg或每日12 mg，或接受安慰剂。主要终点是在第12周银屑病面积和严重程度指数（PASI）评分从基线降低75%或更高（评分越高表明银屑病的严重程度越高）。在第12周，安慰剂组PASI评分降低75%或以上的患者百分比为7%（45例患者中的3例），BMS-986165 3 mg隔日给药组为9%（44例患者中的4例）（与安慰剂相比P = 0.49），每日3 mg给药组为39%（44例患者中的17例）（P = 0.05）。
BACKGROUNDTyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis.METHODSWe conducted a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in adults with moderate-to-severe psoriasis, excluding patients with a previous lack of response to agents targeting cytokine signaling through the same tyrosine kinase pathway. Patients were randomly assigned to receive the drug orally at a dose of 3 mg every other day, 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily or to receive placebo. The primary end point was a 75% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (higher scores indicate greater severity of psoriasis).RESULTSA total of 267 patients received at least one dose in an intervention group of the trial. At week 12, the percentage of patients with a 75% or greater reduction in the PASI score was 7% (3 of 45 patients) with placebo, 9% (4 of 44 patients) with 3 mg of BMS-986165 every other day (P = 0.49 vs. placebo), 39% (17 of 44 patients) with 3 mg daily (P