Background

Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis.

Methods

IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16–44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with , number .

Findings

Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5–32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6–30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9–61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B.

Interpretation

Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis.

Funding

AbbVie and Boehringer Ingelheim.

中文翻译：

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Risankizumab与阿达木单抗在中度至重度斑块型牛皮癣（IMMvent）患者中的比较：一项随机，双盲，积极比较者对照的3期临床试验

背景

牛皮癣是一种自身免疫性疾病，全世界约有1亿人受到这种疾病的影响，并且可以通过抗细胞因子治疗来缓解这种疾病。我们旨在比较risankizumab和adalimumab在中度至重度斑块状牛皮癣患者中的疗效和安全性。

方法

IMMvent是一项在11个国家/地区的66个诊所中完成的第3阶段，随机，双盲，主动比较器对照试验。符合条件的患者年龄在18岁或以上，患有中度至重度慢性斑块状牛皮癣。使用互动反应技术将患者随机分配为1：1，以在第0和4周皮下接受150 mg risankizumab或在随机分组下皮下接受80 mg阿达木单抗，然后在第1、3、5周和之后每隔一周在16-每周双盲治疗期（A部分）。在16-44周（B部分）中，将阿达木单抗中间应答者按1：1重新随机分配，以继续使用40 mg阿达木单抗或改用150 mg risankizumab。在A部分中，对参与者和研究者进行掩饰以研究治疗方法。随机分组按体重和先前的肿瘤坏死因子抑制剂暴露进行分层。A部分的主要共同终点比基线提高了90％（PASI 90），第16周的Physician's Global Global静态评估（sPGA）得分为0或1，而B部分的第44周的PASI 90为无反应（无反应）归因）。在意向性治疗人群中进行了功效分析，在安全性人群中进行了安全性分析（所有接受至少一剂研究药物或安慰剂的患者）。这项研究的编号是。在意向性治疗人群中进行了功效分析，在安全性人群中进行了安全性分析（所有接受至少一剂研究药物或安慰剂的患者）。这项研究的编号是。在意向性治疗人群中进行了功效分析，在安全性人群中进行了安全性分析（所有接受至少一剂研究药物或安慰剂的患者）。这项研究的编号是。

发现

在2016年3月31日至2017年8月24日之间，随机分配605名患者接受risankizumab（n = 301，50％）或adalimumab（n = 304，50％）。risankizumab组中的294（98％）名患者和阿达木单抗组中的291（96％）名患者完成了A部分，并且53名患者中的51名（96％）重新随机选择使用risankizumab，56名患者中的51名（91％）重新接受了治疗。随机分组以继续完成阿达木单抗的B部分治疗。在第16周时，接受risankizumab的301例患者中的218名（72％）和接受adalimumab的304例患者中144例（47％）达到了PASI（调整后的绝对差异24·9％[95％CI [17·5–32·4]； p <0·0001），在252名（84％）接受利沙珠单抗的患者和252名（60％）接受阿达木单抗的患者中sPGA得分为0或1（调整后的绝对差异23·3） ％[16·6–30·1]； p <0·0001）。在B部分中，阿达木单抗中间应答者中，

解释

在中度至重度斑块状牛皮癣患者中，Risankizumab在提供皮肤清除作用方面显示出比阿达木单抗明显更高的功效。对于从阿达木单抗转为risankizumab的患者，未发现额外的安全隐患。risankizumab的治疗为牛皮癣的长期治疗提供了灵活性。

资金

艾伯维（AbbVie）和勃林格殷格翰（Boehringer Ingelheim）。