Johns Hopkins Division of Allergy & Clinical Immunology, Baltimore, Md; Creticos Research Group, Crownsville, MD.
Department of Immunology & Allergy, Ordu University Education & Research Hospital, Ordu, Türkiye.
J Allergy Clin Immunol Pract. 2024 Jun;12(6):1415-1427. doi: 10.1016/j.jaip.2024.04.034. Epub 2024 Apr 27.
Allergen immunotherapy (AIT) is a recognized key therapeutic modality for the treatment of allergic respiratory disease. Definitive studies have provided evidence-based data to demonstrate its effectiveness in allergic rhinitis and asthma due to the inhalation of proteinaceous allergic substances from specific seasonal pollens, dust mites, animal allergens, and certain mold spores. Over the ensuing decades, laboratory investigations have provided objective evidence to demonstrate immunologic changes, including production of protective IgG antibody, suppression of IgE antibody, upregulation of regulatory T cells, and induction of a state of immune tolerance to the offending allergen(s). Tangential to this work were carefully designed clinical studies that defined allergen dose and duration of treatment, established the importance of preparing extracts with standardized allergens (or well-defined extracts) based on major protein moieties, and used allergen provocation models to demonstrate efficacy superior to placebo. In the United States, the use of subcutaneous immunotherapy extracts for AIT was grandfathered in by the Food and Drug Administration based on expert literature review. In contrast, sublingual tablet immunotherapy underwent formal clinical development programs (phase I-III clinical trials) that provided the necessary clinical evidence for safety and efficacy that led to regulatory agency approvals for the treatment of allergic rhinitis in properly characterized patients with allergy. The allergy specialist's treatment options currently include traditional subcutaneous AIT and specific sublingual tablets approved for grass, ragweed, house dust mites, trees belonging to the birch-homologous group, and Japanese cedar. Tangential to this are sublingual drops that are increasingly being used off-label (albeit not approved by the Food and Drug Administration) in the United States. This article will review the evidence-based literature supporting the use of these forms of AIT, as well as focus on several current controversies and gaps in our knowledge base that have relevance for the appropriate selection of patients for treatment with specific AIT.
变应原免疫疗法（AIT）是治疗过敏性呼吸道疾病的公认重要治疗方法。有明确的研究提供了基于证据的数据，证明其对吸入特定季节性花粉、尘螨、动物过敏原和某些霉菌孢子等蛋白质变应原引起的过敏性鼻炎和哮喘的有效性。在随后的几十年中，实验室研究提供了客观证据，证明了免疫变化，包括保护性 IgG 抗体的产生、IgE 抗体的抑制、调节性 T 细胞的上调以及对过敏原的免疫耐受状态的诱导。与这项工作相关的是精心设计的临床研究，这些研究定义了变应原剂量和治疗时间，确定了使用标准化变应原（或明确定义的提取物）制备提取物的重要性，以及使用变应原激发模型证明疗效优于安慰剂。在美国，基于专家文献综述，食品和药物管理局允许皮下免疫疗法提取物用于 AIT。相比之下，舌下片剂免疫疗法经过了正式的临床开发计划（I-III 期临床试验），这些计划提供了安全性和有效性的必要临床证据，从而为适当特征的过敏患者的过敏性鼻炎治疗获得了监管机构的批准。过敏专家的治疗选择目前包括传统的皮下 AIT 和特定的舌下片剂，这些片剂已获得批准用于治疗草、豚草、屋尘螨、桦木同源组的树木和日本雪松过敏。与之相关的是舌下滴剂，这些滴剂越来越多地被非标签使用（尽管未获得食品和药物管理局批准）在美国。本文将回顾支持使用这些形式的 AIT 的循证文献，并重点介绍我们知识基础中的几个当前争议和差距，这些争议和差距与为特定 AIT 治疗选择适当患者有关。
