Greater cumulative benefits from ixekizumab versus ustekinumab treatment over 52 weeks for patients with moderate-to-severe psoriasis in a randomized, double-blinded phase 3b clinical trial

Background: Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, has shown superiority to ustekinumab (UST) and etanercept in skin clearance from randomized clinical trials in patients with moderate-to-severe psoriasis. Objective: To compare cumulative benefits of IXE versus UST over 52 weeks of treatment. Methods: Cumulative clinical benefit of IXE and UST was assessed by evaluating the area under the curve (AUC) for responders of Psoriasis Area and Severity Index (PASI), itch numeric rating scale (Itch NRS), and Dermatology Life Quality Index (DLQI) outcomes over 52 weeks using data from IXORA-S trial comparing IXE (N = 136) and UST (N = 166). Normalized cumulative benefit was calculated to obtain the percentage of the maximum AUC for each outcome measure. Missing values were imputed using non-responder imputation. Results: Significantly greater cumulative benefits were obtained for IXE compared with UST. Normalized cumulative benefit with IXE versus UST for PASI 75/90/100, Itch NRS (0), and DLQI (0,1) were 83.1% and 67.6%; 68.9% and 46.5%; 41.1% and 23.4%; 40.4% and 30.9%; and 62.2% and 46.6%, respectively. Cumulative clinical benefit ratios for IXE:UST were 1.23 for PASI 75, 1.48 for PASI 90, and 1.76 for PASI 100, indicating an increase in the cumulative clinical benefit for IXE versus UST as the clearance levels increased. Conclusions: IXE showed greater cumulative clinical benefit than UST.

背景：伊克来珠单抗（IXE），一种高亲和力的人源化单克隆抗体，选择性靶向白介素-17A，在针对中度至重度银屑病患者的随机临床试验中，其在皮肤清除率方面优于乌司奴单抗（UST）和依那西普。目标：比较伊克来珠单抗与乌司奴单抗在52周治疗期间的累积效益。方法：通过评估52周内Psoriasis Area and Severity Index（PASI）评分、瘙痒数值评分量表（Itch NRS）和皮肤病生活质量指数（DLQI）的曲线下面积（AUC）来评估伊克来珠单抗和乌司奴单抗的累积临床效益。使用来自IXORA-S试验的数据进行比较，该试验比较了伊克来珠单抗（N=136）和乌司奴单抗（N=166）。通过标准化累积效益来计算每个结果指标的最大AUC的百分比。缺失值使用非应答者插补法进行估计。结果：与乌司奴单抗相比，伊克来珠单抗的累积效益显著更高。伊克来珠单抗与乌司奴单抗的标准化累积效益分别为：PASI 75/90/100为83.1%和67.6%；瘙痒NRS（0）为68.9%和46.5%；DLQI（0,1）为41.1%和23.4%；40.4%和30.9%；以及62.2%和46.6%。伊克来珠单抗与乌司奴单抗的累积临床效益比分别为：PASI 75为1.23，PASI 90为1.48，PASI 100为1.76，表明随着清除率的提高，伊克来珠单抗相对于乌司奴单抗的累积临床效益有所增加。结论：伊克来珠单抗的累积临床效益优于乌司奴单抗。