Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials-猫眼课题宝

DOI：

10.1016/s0140-6736(18)31713-6

发表时间：

2018-08-25

期刊：

LANCET

影响因子：

168.9

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Gordon, Kenneth B.;Strober, Bruce;Bachelez, Herve

背景：Risankizumab是一种人源化的IgG1单抗，它与白介素23的p19亚单位结合，抑制这一关键细胞因子及其在银屑病炎症中的作用。我们的目的是评估risankizumab与安慰剂或ustekinumab治疗中重度慢性斑块型银屑病患者的疗效和安全性。方法UltIMMa-1和UltIMMa-2是重复的第三阶段，随机、双盲、安慰剂对照和积极对照对照试验，在澳大利亚、奥地利、比利时、加拿大、捷克共和国、法国、德国、日本、墨西哥、波兰、葡萄牙、韩国、西班牙和美国的139个地点进行。符合条件的患者为18岁或以上，患有中到重度慢性斑块型银屑病。在每项研究中，患者根据体重和以前接触肿瘤坏死因子抑制剂的情况进行分层，并利用互动反应技术随机分配(3：1：1)，接受150毫克risankizumab、45 mg或90 mg ustekinumab(按标签重量计算)或安慰剂。在为期16周的双盲治疗(A部分)之后，最初被分配给安慰剂的患者在第16周转为150毫克risankizumab；其他患者继续他们最初的随机治疗(B部分，双盲，第16-52周)。研究药物在A部分的0周和4周以及B部分的16周、28周和40周皮下注射。共同主要终点是指在16周时牛皮癣面积严重指数(PASI 90)和静态医生总体评估(SPGA)得分为0或1(无反应者归责)的患者的比例。所有疗效分析都是在意向治疗人群中进行的。这些试验在ClinicalTrials.gov注册，编号为NCT02684370(UltIMMa-1)和NCT02684357(UltIMMa-2)，并已完成。2016年2月24日至2016年8月31日期间，UltIMMa-1的506名患者被随机分配接受150 mg risankizumab(n=304)、45 mg或90 mg ustekinumab(n=100)或安慰剂(n=102)。在2016年3月1日至2016年8月30日期间，UltIMMa-2中的491名患者被随机分配到接受150 mg risankizumab(n=294)、45 mg或90 mg ustekinumab(n=99)或安慰剂(n=98)。两项研究都达到了共同的主要终点。在UltIMMa-1的第16周，接受risankizumab治疗的229名患者(75.3%)达到了PASI 90，而接受安慰剂(安慰剂调整后的差异为70.3%[95%CI 64.0-76.7])和接受ustekinumab(ustekinumab调整后的差异33.5%[22.7-44.3])的患者中有5名(4.9%)达到了PASI 90；

Background Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis.Methods UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16-52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed.Findings Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n= 304), 45 mg or 90 mg ustekinumab (n= 100), or placebo (n= 102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n= 294), 45 mg or 90 mg ustekinumab (n= 99), or placebo (n= 98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75.3%) patients receiving risankizumab versus five (4.9%) receiving placebo (placebo-adjusted difference 70.3% [95% CI 64.0-76.7]) and 42 (42.0%) receiving ustekinumab (ustekinumab-adjusted difference 33.5% [22.7-44.3]; p

Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials

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