Background

The impact of dupilumab, an anti–interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown.

Objectives

To assess T-cell–dependent and T-cell–independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety.

Methods

In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16.

Results

In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P < .001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo.

Limitation

Patients’ prior vaccination status was not available before enrollment.

Conclusion

Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.

中文翻译：

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Dupilumab不会影响疫苗诱导的免疫相关性：一项针对中度至重度特应性皮炎的成人的随机，安慰剂对照试验

背景

尚不知道dupilumab（一种抑制IL-4和IL-13信号传导的抗白介素（IL）4受体α抗体）对特应性皮炎（AD）患者的疫苗反应的影响。

目标

为了评估针对破伤风和脑膜炎球菌疫苗的T细胞依赖性和T细胞依赖性体液免疫反应，IgE血清转化为破伤风类毒素，白喉类毒素减少和无细胞百日咳（Tdap）疫苗接种，以及dupilumab的有效性和安全性。

方法

在一项随机，双盲，安慰剂对照研究（NCT02210780）中，患有中度至重度AD的成年人每周接受dupilumab（300 mg）或安慰剂治疗16周，并在第12周单剂Tdap和四价脑膜炎球菌多糖疫苗主要终点指标是在第16周对破伤风类毒素获得满意IgG应答的患者比例。

结果

总共178名患者完成了研究。在dupilumab和安慰剂组中，破伤风（分别为83.3％和83.7％）和脑膜炎球菌多糖（分别为86.7％和87.0％）达到了相似的阳性免疫反应（抗体滴度增加了4倍，或抗体滴度≥8）。 ， 分别）。Dupilumab显着降低总血清IgE；大多数接受dupilumab治疗的患者在第32周时均为Tdap-IgE血清阴性（62.2％dupilumab和34.8％安慰剂）。Dupilumab改善了关键的AD疗效终点（P  <.001）。dupilumab的注射部位反应和结膜炎更为常见。安慰剂可使AD发作更为频繁。

局限性

入组前尚无患者先前的疫苗接种状况。

结论

Dupilumab不会影响对所研究疫苗的反应，与安慰剂相比，IgE显着降低，AD严重程度的测量得到改善，并且具有可接受的安全性。