Department of Dermatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Adv Ther. 2023 Sep;40(9):3804-3816. doi: 10.1007/s12325-023-02575-1. Epub 2023 Jun 25.
We evaluated the pharmacokinetics (PK), safety, and efficacy of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, in Chinese patients with moderate-to-severe psoriasis.
In this phase 1, multicenter, open-label study, adults (≥ 18 years) diagnosed with moderate-to-severe plaque psoriasis for ≥ 6 months involving ≥ 10% of their body surface area received ixekizumab 80 mg by subcutaneous injection and were observed for 20 weeks (single-dose phase) and then an initial dose of 160 mg followed by randomization (1:1) to 80 mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE Q4W) for an 8-week treatment period (multiple-dose phase).
The median time to maximum observed ixekizumab concentrations occurred 2-4 days after dosing and the geometric mean half-life was 15-16 days, after single (n = 12) and multiple (n = 29) doses. Approximately linear pharmacokinetics were observed between the 80 and 160 mg single doses. Steady-state systemic exposure to ixekizumab during a dosing interval was similar with the IXE Q2W and IXE Q4W regimens, with estimates of 224 µg·day/mL and 213 µg·day/mL for the area under the concentration-time curve from time 0 to 14 days post-dose and 0 to 28 days post-dose, respectively. Safety was consistent with the established safety profile of ixekizumab. At week 12 after multiple doses, the proportions of patients achieving a 75% or 90% improvement in Psoriasis Area and Severity Index score were 100% and 86% for IXE Q2W, respectively, and 93% and 80% for IXE Q4W, respectively. A Static Physician's Global Assessment score of 0 or 1 was achieved in 100% and 87% with IXE Q2W and IXE Q4W, respectively.
The PK of ixekizumab in Chinese patients with moderate-to-severe plaque psoriasis was comparable to findings in global populations. After IXE Q2W or IXE Q4W for 12 weeks, clinically relevant treatment responses and an acceptable safety profile were observed.
Clinicaltrials.gov (NCT03073213).
我们评估了 ixekizumab 的药代动力学（PK）、安全性和疗效，ixekizumab 是一种高亲和力的单克隆抗体，可选择性靶向白细胞介素-17A，用于中国中重度斑块状银屑病患者。
在这项 1 期、多中心、开放标签研究中，诊断为中重度斑块状银屑病的成年人（≥ 18 岁），病程≥6 个月，受累面积≥10%体表面积，接受皮下注射 80mg ixekizumab，并观察 20 周（单次剂量阶段），然后给予初始剂量 160mg，随后随机（1:1）分为 ixekizumab 每 2 周（IXE Q2W）或每 4 周（IXE Q4W）一次，治疗 8 周（多次剂量阶段）。
单次（n=12）和多次（n=29）剂量后，最大观察到 ixekizumab 浓度的中位时间为给药后 2-4 天，几何平均半衰期为 15-16 天。单次剂量的 80 和 160mg 之间观察到近似线性 PK。在给药间隔期间，ixekizumab 的稳态全身暴露与 IXE Q2W 和 IXE Q4W 方案相似，分别为剂量后 14 天和 28 天的时间-浓度曲线下面积 0 至 14 天和 0 至 28 天的估计值为 224μg·day/mL 和 213μg·day/mL。安全性与 ixekizumab 的既定安全性特征一致。多次给药后 12 周，IXE Q2W 组分别有 100%和 86%的患者达到银屑病面积和严重程度指数评分改善 75%或 90%，IXE Q4W 组分别有 93%和 80%的患者达到上述疗效，IXE Q2W 和 IXE Q4W 组分别有 100%和 87%的患者达到静态医生整体评估评分 0 或 1。
中国中重度斑块状银屑病患者的 ixekizumab PK 与全球人群的结果相当。IXE Q2W 或 IXE Q4W 治疗 12 周后，观察到有临床意义的治疗反应和可接受的安全性特征。
Clinicaltrials.gov（NCT03073213）。
