Treatment of chronic autoimmune urticaria with omalizumab
Treatment of chronic autoimmune urticaria with omalizumab
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DOI：
10.1016/j.jaci.2008.07.006
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发表时间：
2008-09-01
影响因子：
14.2
通讯作者：
Zeldin, Robert K.
中科院分区：
文献类型：
--
作者：
Kaplan, Allen P.;Joseph, Kusumam;Zeldin, Robert K.
背景：大约45%的慢性荨麻疹患者具有针对高亲和力IgE受体a亚基的IgG自身抗体（慢性自身免疫性荨麻疹，CAU），导致皮肤肥大细胞和嗜碱性粒细胞活化。用omalizumab治疗过敏性哮喘可迅速降低游离IgE水平，随后降低Fc，这是肥大细胞和嗜碱性细胞上RI表达的一个因素。如果这种情况发生在CAU中，IgE受体通过自身抗体交联的可能性就会降低，从而降低细胞活化和荨麻疹/血管性水肿。目的：探讨奥玛珠单抗治疗CAU症状患者抗组胺治疗后的疗效。方法：通过嗜碱性粒细胞组胺释放试验和自体皮肤试验鉴定的12例CAU患者，尽管使用抗组胺药，但症状持续至少6周，接受安慰剂治疗4周，随后每2或4周接受奥玛珠单抗治疗（>= 0.016mg/kg/IU mL(-1) IgE /月），共16周。主要疗效变量是从基线到奥玛珠单抗治疗最后4周的平均荨麻疹活动评分（UAS， 0-9分）的变化。评估抢救用药和生活质量的变化。结果：平均UAS从基线到奥玛珠单抗治疗的最后4周显著下降（7.50 +/- 1.78至2.66 +/- 3.31,-4.84 +/- 2.86,P = 0.0002）。7例患者症状完全缓解。4例患者平均UAS下降，但荨麻疹持续存在。一名患者没有反应。抢救用药明显减少，生活质量提高。没有报告或观察到不良反应。结论：这项探索性的概念验证研究表明，omalizumab是抗组胺药耐药CAU的有效治疗方法。
Background: Approximately 45% of patients with chronic urticaria have an IgG autoantibody directed to the a-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria, CAU) leading to cutaneous mast cell and basophil activation. Treatment of allergic asthma with omalizumab produces rapid reduction in free IgE levels and subsequent decrease in Fc is an element of RI expression on mast cells and basophils. If this occurs in CAU, cross-linking of IgE receptors by autoantibody would be less likely, reducing cell activation and urticaria/angioedema. Objective: To investigate the efficacy of omalizumab in patients with CAU symptomatic despite antihistamine therapy.Methods: Twelve patients with CAU, identified by basophil histamine release assay and autologous skin test, with persistent symptoms for at least 6 weeks despite antihistamines, were treated with placebo for 4 weeks followed by omalizumab ( >= 0.016mg/kg/IU mL(-1) IgE per month) every 2 or 4 weeks for 16 weeks. Primary efficacy variable was change from baseline to the final 4 weeks of omalizumab treatment in mean Urticaria Activity Score (UAS, 0-9 scale). Changes in rescue medication use and quality of life were assessed.Results: Mean UAS declined significantly from baseline to the final 4 weeks of omalizumab treatment (7.50 +/- 1.78 to 2.66 +/- 3.31, -4.84 +/- 2.86, P =.0002). Seven patients achieved complete symptom resolution. In 4 patients, mean UAS decreased, but urticaria persisted. One patient did not respond. Rescue medication use was reduced significantly, and quality of life improved. No adverse effects were reported or observed.Conclusion: This exploratory proof of concept study suggests omalizumab is an effective therapy for CAU resistant to antihistamines.