Maguire P, Nicodemus C, Robinson D, Aaronson D, Umetsu D T
Department of Pediatrics, Stanford University, Stanford, California 94305, USA.
Clin Immunol. 1999 Dec;93(3):222-31. doi: 10.1006/clim.1999.4795.
Conventional immunotherapy for cat allergy is effective in reducing cat allergy symptoms in many patients, but this type of immunotherapy can cause severe reactions, including anaphylaxis, and often requires years of injections for successful desensitization. To improve the efficacy of immunotherapy for cat allergic patients, synthetic cat allergen peptides (ALLERVAX CAT) were generated, based on analysis of the immunodominant T cell epitopes of cat allergen. These peptides lack the tertiary structure of native Fel d1 and possess a significantly reduced capacity to bind to Fel d1-specific IgE. Using these peptides, we performed a multicenter, randomized, double-blind, placebo-controlled study of 133 cat allergic patients chronically exposed to cats or who had failed previous conventional cat immunotherapy. We evaluated the safety of ALLERVAX CAT treatment and determined whether ALLERVAX CAT treatment improved tolerance to cat allergen, as measured by symptom analysis and pulmonary function testing. Three of the ALLERVAX CAT-treated patients required systemic epinephrine for adverse reactions, but the frequency of all adverse reactions in both groups was not statistically different from that of the placebo group. The majority of adverse events were "late" events, most commonly associated with respiratory symptoms, and these events declined with successive injections. ALLERVAX CAT given at a dose of 750 microg/dose improved pulmonary function in patients with reduced baseline FEV1, and global evaluation of the subjects' ability to tolerate cats improved significantly in the actively treated groups relative to placebo. Thus, although therapy with ALLERVAX CAT is associated with some adverse events in patients with severe cat sensitivity, such therapy is an effective approach for the management of cat allergy, since it improves tolerance to cats and improves pulmonary function in cat allergic patients with reduced FEV1.
传统的猫过敏免疫疗法对许多患者减轻猫过敏症状有效，但这种免疫疗法可能会引发严重反应，包括过敏反应，且往往需要数年注射才能成功脱敏。为提高猫过敏患者免疫疗法的疗效，基于对猫过敏原免疫显性T细胞表位的分析，制备了合成猫过敏原肽（ALLERVAX CAT）。这些肽缺乏天然Fel d1的三级结构，与Fel d1特异性IgE结合的能力显著降低。我们使用这些肽对133名长期接触猫或之前传统猫免疫疗法失败的猫过敏患者进行了一项多中心、随机、双盲、安慰剂对照研究。我们评估了ALLERVAX CAT治疗的安全性，并通过症状分析和肺功能测试确定ALLERVAX CAT治疗是否提高了对猫过敏原的耐受性。3名接受ALLERVAX CAT治疗的患者因不良反应需要全身性肾上腺素治疗，但两组所有不良反应的发生率与安慰剂组相比无统计学差异。大多数不良事件为“迟发”事件，最常见的与呼吸道症状相关，且这些事件随着连续注射而减少。剂量为750微克/剂量的ALLERVAX CAT改善了基线FEV1降低患者的肺功能，与安慰剂相比，积极治疗组受试者对猫的耐受能力的总体评估有显著改善。因此，尽管ALLERVAX CAT治疗在严重猫敏感患者中会伴随一些不良事件，但这种治疗是管理猫过敏的有效方法，因为它提高了对猫的耐受性，并改善了FEV1降低的猫过敏患者的肺功能。
