Eli Lilly and Company, Indianapolis, IN, USA.
Eli Lilly and Company, Windlesham, UK.
BioDrugs. 2017 Dec;31(6):545-554. doi: 10.1007/s40259-017-0249-y.
Ixekizumab (IXE) is an interleukin (IL)-17A antagonist approved for the treatment of adults with moderate-to-severe psoriasis.
The objective of this study was to determine if the immune response to tetanus and pneumococcal vaccines in healthy subjects administered IXE was noninferior to control.
In a randomized, open-label, parallel-group study, adult subjects received vaccinations alone (N = 42, control) or in combination with 160 mg IXE subcutaneously 2 weeks prior to vaccination and 80 mg IXE on the day of vaccination (N = 41, IXE). Response to tetanus vaccination was defined as anti-tetanus antibodies ≥ 1.0 IU and a ≥ 1.5-fold increase if baseline was ≤ 1.0 IU or a ≥ 2.5-fold increase if baseline was > 1.0 IU. Response to pneumococcal vaccination was defined as a ≥ 2-fold increase from baseline in anti-pneumococcal antibodies against > 50% of the 23 serotypes. The primary outcomes were the percentages of patients with a response to the tetanus and pneumococcal vaccines 4 weeks after vaccination. A noninferiority analysis of IXE to control using a 40% margin was evaluated for the primary outcomes. Safety and pharmacokinetics were also assessed.
IXE (38 completers) was noninferior to control (41 completers) based on the difference in the proportion of responders to tetanus [1.4%; 90% confidence interval (CI) - 16.6 to 19.2] and pneumococcal (- 0.8%; 90% CI - 12.9 to 11.0) vaccines. Twenty subjects (14 IXE, six control) reported 43 mild treatment-emergent adverse events.
IXE does not suppress the humoral immune response to non-live vaccines and was well tolerated in healthy subjects. ClinicalTrial.gov identifier: NCT02543918.
依奇珠单抗（IXE）是一种白细胞介素（IL）-17A 拮抗剂，已获批用于治疗中重度斑块状银屑病成人患者。
本研究旨在确定健康受试者接受依奇珠单抗治疗后，破伤风和肺炎球菌疫苗的免疫应答是否与对照组无差异。
在一项随机、开放标签、平行组研究中，成年受试者单独接种疫苗（N=42，对照组）或在接种疫苗前 2 周皮下给予 160mg 依奇珠单抗和接种疫苗当天给予 80mg 依奇珠单抗（N=41，IXE 组）。破伤风疫苗应答定义为破伤风抗体≥1.0IU，且基线≤1.0IU 时增加≥1.5 倍，或基线>1.0IU 时增加≥2.5 倍。肺炎球菌疫苗应答定义为针对 23 种血清型中≥50%的血清型的肺炎球菌抗体与基线相比增加≥2 倍。主要结局为接种疫苗后 4 周时破伤风和肺炎球菌疫苗的应答患者比例。使用 40%的边界值对依奇珠单抗与对照组的主要结局进行非劣效性分析。还评估了安全性和药代动力学。
基于破伤风[1.4%；90%置信区间（CI）-16.6 至 19.2]和肺炎球菌（-0.8%；90%CI-12.9 至 11.0）疫苗应答者比例的差异，依奇珠单抗（38 例完成者）与对照组（41 例完成者）相比非劣效。20 名受试者（14 名依奇珠单抗，6 名对照组）报告了 43 起轻度治疗后出现的不良事件。
依奇珠单抗不会抑制非活疫苗的体液免疫应答，且在健康受试者中耐受良好。临床试验注册编号：NCT02543918。
