背景:Lebrikizumab,一种高亲和力IgG4单克隆抗体,以高结合亲和力和低解离速率选择性抑制白细胞介素-13,防止白细胞介素-4Rα/白细胞介素-13Rα1异源二聚体受体信号复合物的形成。在这里,我们报告了lebrikizumab对中度至重度特应性皮炎(AD)成年患者两种非活疫苗反应的影响。
方法:ADopt-VA(NCT04626297)是双盲,安慰剂对照,平行组,16周,评估lebrikizumab治疗对非活疫苗免疫反应的影响的3期随机研究,与安慰剂相比,lebrikizumab的疗效和安全性。符合条件的患者包括18至55岁患有中度至重度慢性AD的成年人,他们被随机分配1:1每2周250mglebrikizumab或安慰剂,并根据疾病严重程度进行分层。主要终点是对破伤风类毒素的加强反应和对脑膜炎球菌结合疫苗(MCV)的阳性抗体反应的发展,施用相应疫苗后4周。
结果:在第16周时,lebrikizumab组(n=78/106)中73.6%的患者实现了Tdap增强反应,而安慰剂组(n=58/79)中73.4%的患者实现了Tdap增强反应。在lebrikizumab组中86.9%的患者(n=86/99)和安慰剂组中75.0%的患者(n=60/80)中观察到MCV疫苗反应。在第16周,40.6%(n=51/125)的lebrikizumab治疗患者和18.9%(n=23/122)的安慰剂患者(p<0.001)实现了IGA0,1与基线≥2点改善。在接受lebrikizumab治疗的患者中,在第16周达到EASI75的患者比例更高(58.0%,n=72/125)与安慰剂(32.7%,n=40/122,p<0.001)。
结论:在本研究中,使用lebrikizumab治疗并不影响对非活疫苗Tdap和MCV的反应。与安慰剂相比,Lebrikizumab治疗在多个终点具有显著程度的疗效。
背景:ClinicalTrials.gov标识符NCT04626297。
BACKGROUND: Lebrikizumab, a high-affinity IgG4 monoclonal antibody that selectively inhibits interleukin-13 with high binding affinity and slow dissociation rate, prevents the formation of the interleukin-4Rα/interleukin-13Rα1 heterodimer receptor signaling complex. Here we report the impact of lebrikizumab on responses to two non-live vaccines in adult patients with moderate-to-severe atopic dermatitis (AD).
METHODS: ADopt-VA (NCT04626297) was a double-blind, placebo-controlled, parallel-group, 16-week, phase 3 randomized study to assess the impact of lebrikizumab treatment on non-live vaccine immune responses, and efficacy and safety of lebrikizumab compared with placebo. Eligible patients included adults from 18 to 55 years of age with moderate-to-severe chronic AD who were randomly assigned 1:1 to lebrikizumab 250 mg every 2 weeks or placebo and stratified according to disease severity. The primary endpoints were the development of a booster response to tetanus toxoid and a positive antibody response to meningococcal conjugate vaccine (MCV), 4 weeks after administration of the corresponding vaccine.
RESULTS: At week 16, 73.6% of patients in the lebrikizumab group (n = 78/106) achieved Tdap booster response compared with 73.4% of patients in the placebo group (n = 58/79). MCV vaccine response was observed in 86.9% of patients in the lebrikizumab group (n = 86/99) and 75.0% of patients in the placebo group (n = 60/80). At week 16, IGA 0,1 with ≥ 2-point improvement from baseline was achieved by 40.6% (n = 51/125) of patients treated with lebrikizumab and 18.9% (n = 23/122) of patients who received placebo (p < 0.001). There was a higher proportion of patients achieving EASI 75 at week 16 in the lebrikizumab-treated patients (58.0%, n = 72/125) compared with placebo (32.7%, n = 40/122, p < 0.001).
CONCLUSIONS: Treatment with lebrikizumab did not impact response to non-live vaccines Tdap and MCV in this study. Lebrikizumab treatment had a significant degree of efficacy compared to placebo across multiple endpoints.
BACKGROUND: ClinicalTrials.gov identifier NCT04626297.