Psoriasis Center, Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Department of Dermatology, Medical Center, Medical University Center, Mainz, Germany.
Br J Dermatol. 2023 Sep 15;189(4):381-391. doi: 10.1093/bjd/ljad186.
Monoclonal antibodies to interleukin (IL)-17 have shown strong efficacy in patients with psoriasis. Izokibep is a unique IL-17A inhibitor with a small molecular size and favourable distribution to sites of inflammation.
To evaluate the dose response, efficacy and safety of izokibep in patients with plaque psoriasis.
In this double-blind, randomized, phase II dose-finding study (AFFIRM-35) in adults with moderate-to-severe plaque psoriasis and inadequate response to two or more standard therapies, patients were randomized (1:1:1:1:1) to placebo or izokibep 2, 20, 80 or 160 mg every 2 weeks for 12 weeks. During the remainder of the 52-week core study, patients given placebo were switched to izokibep 80 mg, and dosing intervals were adapted based on Psoriasis Area and Severity Index (PASI) scores for all patients. The core study was followed by two optional consecutive 1-year extension periods for a total duration of 3 years. The primary endpoint was a 90% reduction in PASI score (PASI 90) at week 12. Additional efficacy outcomes and adverse event (AE) rates were evaluated.
In total, 109 patients were randomized [safety set, n = 108 (one exclusion criteria failure); full analysis set, n = 106]. At week 12, PASI 90 response rates were 0%, 5%, 19%, 71% and 59% for the placebo, 2-, 20-, 80- and 160-mg izokibep groups, respectively. Rapid dose-dependent improvements were also observed across other efficacy outcomes. During the placebo-controlled period, AEs in the izokibep groups were similar to placebo except for mild injection site reactions. AEs were generally mild to moderate and the drug was well tolerated. Izokibep maintained efficacy at the higher dosage groups for up to 3 years, with no new safety signals.
Data from this phase II study indicate that izokibep is well tolerated and efficacious in the treatment of plaque psoriasis. Higher doses or more frequent dosing could be explored to further enhance response rates.
白细胞介素（IL）-17 的单克隆抗体已在银屑病患者中显示出强大的疗效。Izokibep 是一种独特的 IL-17A 抑制剂，具有小分子大小和有利于炎症部位分布的特点。
评估 izokibep 在斑块状银屑病患者中的剂量反应、疗效和安全性。
在这项针对中重度斑块状银屑病且对两种或两种以上标准治疗反应不足的成年人的双盲、随机、II 期剂量发现研究（AFFIRM-35）中，患者按 1:1:1:1:1 的比例随机分配至安慰剂或 izokibep 2、20、80 或 160mg，每 2 周一次，共 12 周。在 52 周核心研究的其余时间内，给予安慰剂的患者转换为 izokibep 80mg，根据所有患者的银屑病面积和严重程度指数（PASI）评分调整给药间隔。核心研究后，进行了两个可选的连续 1 年扩展期，总持续时间为 3 年。主要终点为第 12 周时 PASI 评分降低 90%（PASI 90）。评估了其他疗效终点和不良事件（AE）发生率。
共有 109 名患者入组[安全性集，n=108（1 例排除标准失败）；全分析集，n=106]。第 12 周时，安慰剂、2、20、80 和 160mg izokibep 组的 PASI 90 应答率分别为 0%、5%、19%、71%和 59%。其他疗效终点也观察到快速的剂量依赖性改善。在安慰剂对照期间，izokibep 组的 AE 与安慰剂相似，除了轻度注射部位反应。AE 通常为轻度至中度，药物耐受性良好。izokibep 在高剂量组的疗效可维持长达 3 年，无新的安全性信号。
这项 II 期研究的数据表明，izokibep 治疗斑块状银屑病具有良好的耐受性和疗效。可以探索更高的剂量或更频繁的给药来进一步提高应答率。
