Allergen immunotherapy 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 an 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, utilized
allergen provocation models to demonstrate efficacy superior to placebo. In the U.S., the use of subcutaneous
immunotherapy (SCIT) extracts for allergen immunotherapy (AIT) was grandfathered in by the FDA based on expert literature review. In contrast, sublingual
tablet immunotherapy (SLIT-
tablets) 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 allergic patients. The
allergy specialist's treatment options currently include traditional subcutaneous allergen immunotherapy 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 (SLIT-drops) that are increasingly being used off-label (albeit not FDA-approved) in the U.S. 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.