Influenza and Meningococcal Vaccinations Are Effective in Healthy Subjects Treated with the Interleukin-1β-Blocking Antibody Canakinumab: Results of an Open-Label, Parallel Group, Randomized, Single-Center Study
Influenza and Meningococcal Vaccinations Are Effective in Healthy Subjects Treated with the Interleukin-1β-Blocking Antibody Canakinumab: Results of an Open-Label, Parallel Group, Randomized, Single-Center Study
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DOI：
10.1128/cvi.00175-10
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发表时间：
2010-12-01
影响因子：
--
通讯作者：
Kleinschmidt, A.
中科院分区：
文献类型：
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作者：
Chioato, A.;Noseda, E.;Kleinschmidt, A.
本研究的目的是评估流感和脑膜炎球菌疫苗对暴露于抗白细胞介素-1 β（抗il -1 β）单克隆抗体canakinumab的健康受试者的疗效。这是一项开放标签、平行组、随机、单中心的健康受试者（18 - 45岁）研究。在基线时，测量抗体（Ab）滴度，并将受试者随机（1:1）分配到单次皮下给药300 mg canakinumab （s.c）或不接受治疗（对照组）。2周后，受试者接受灭活、无佐剂流感和结合C组脑膜炎球菌（MenC）疫苗的治疗，肌肉注射（i.m）。主要疗效变量是与对照组相比，接受canakinumab治疗的受试者4周后的反应（>= 3种流感病毒株>= 2中Ab滴度增加2倍）。次要疗效变量是在不同阈值和时间点对疫苗的抗体反应。筛选的112名受试者中有51人被随机分配到canakinumab组（n = 25）或对照组（n = 26）。在canakinumab组和对照组中，4周时针对不同流感病毒株和一种MenC株接种疫苗的抗体反应具有可比性。与对照组的25/25名受试者相比，canakinumab组的24/25名受试者在4周时对流感疫苗的应答（>= 3种血清型中>= 2的抗体滴度增加2倍）显示为主要疗效变量。在评估的不同时间点，两组的抗体反应保持可比性。头痛是最常见的不良反应。研究期间未报告死亡或严重不良事件。我们得出结论，在健康受试者接种无佐剂流感或铝佐剂MenC疫苗后，单剂量300 mg canakinumab s.c.不会影响抗体反应的诱导或持续。
The objective of this study was to evaluate the efficacy of influenza and meningococcal vaccines in healthy subjects exposed to the anti-interleukin-1 beta (anti-IL-1 beta) monoclonal antibody canakinumab. This was an open-label, parallel group, randomized, single-center study of healthy subjects (aged 18 to 45 years). At baseline, antibody (Ab) titers were measured and subjects were randomized (1:1) to a single 300-mg canakinumab dose administered subcutaneously (s.c.) or received no treatment (control group). After 2 weeks, subjects were treated with inactivated, unadjuvanted influenza and conjugated group C meningococcal (MenC) vaccines, administered intramuscularly (i.m.). The primary efficacy variable was the response (>= 2-fold increase in Ab titer in >= 2 of 3 influenza virus strains) after 4 weeks in subjects treated with canakinumab compared to the control group. Secondary efficacy variables were the antibody response to vaccines at different thresholds and time points. Fifty-one of 112 subjects screened were randomized to canakinumab (n = 25) or the control group (n = 26). Antibody responses to vaccinations measured against different influenza virus strains and one MenC strain at 4 weeks were comparable in the canakinumab and control groups. The primary efficacy variable, the response to influenza vaccination (>= 2-fold increase in Ab titer in >= 2 of 3 serotypes) at 4 weeks, was shown in 24/25 subjects in the canakinumab group compared to 25/25 subjects in the control group. Antibody responses remained comparable in the two groups at the different time points assessed. Headache was the most frequently reported adverse event. No deaths or serious adverse events were reported during the study. We concluded that a single dose of 300 mg canakinumab s.c. does not affect the induction or persistence of antibody responses after vaccination with unadjuvanted influenza or alum-adjuvanted MenC vaccines in healthy subjects.