德国汉堡-埃彭多夫大学医学中心和皮肤炎症中心Diamant Thai团队比较了一种新靶向药Risankizumab与阿达木单抗治疗中重度斑块性银屑病（IMMvent）的疗效：一项随机、双盲、主动对照的临床3期试验。 该研究于2019年8月17日发表于国际一流学术期刊《柳叶刀》上。

2016年3月31日至2017年8月24日，605名患者被随机分配至Risankizumab治疗组（301例）或阿达木单抗治疗组（304例）。Risankizumab组的294例（98%）和阿达木单抗组的291例（96%）完成了A部分为期16周的治疗。在第16-44周（B部分），阿达木单抗中期应答的患者被重新分组，risankizumab组53例患者中51例（96%）完成治疗，阿达木单抗组56例患者中51例（91%）完成治疗。观察指标为银屑病斑块减少90%（Pasi 90）和银屑病静态临床医师整体评估（sPGA）评分为0或1。

在第16周，Risankizumab组中有218例（72%）获得PASI 90，而阿达木单抗组中有144例（47%），差异显著。Risankizumab组中有252例（84%）的sPGA得分为0或1分，而阿达木单抗组中有183例（60%），差异显著。B部分，阿达木单抗中期应答者中，Risankizumab组中有35例（66%）患者获得PASI 90，而阿达木单抗组中为12例（21%）。A部分Risankizumab组中有168例（56%）不良反应，阿达木单抗组中有179例（57%）；B部分Risankizumab组中有40例（75%）不良反应，阿达木单抗组中有37例（66%）。

在中重度斑块型银屑病患者中，Risankizumab的皮肤清除率明显高于阿达木单抗，且相对安全。Risankizumab为长期治疗银屑病提供了一种新选择。

据悉，银屑病是一种自身免疫性疾病，全球约有1亿人受其影响，可通过抗细胞因子治疗来加以改善。

附：英文原文

Title: Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial

Author: Prof Kristian Reich, MD, Melinda Gooderham, MD, Prof Diamant Thaçi, MD, Jeffrey J Crowley, MD, Caitriona Ryan, MD, Prof James G Krueger, MD, Prof Tsen-Fang Tsai, MD, Mary Flack, MD, Yihua Gu, MS, David A Williams, MD, Prof Elizabeth H Z Thompson, PhD, Prof Carle Paul, MD

Issue&Volume: Volume 394 Number 10198, 17 August 2019

Summary: 

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 ClinicalTrials.gov, number NCT02694523.

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.

DOI: https://doi.org/10.1016/S0140-6736(19)30952-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30952-3/fulltext#