Allergen immunotherapy is highly effective in treating patients with IgE-mediated allergic rhinitis and asthma, with proven long-term benefits that may persist for years after discontinuation. Subcutaneous immunotherapy remains the gold standard whereas sublingual immunotherapy represents an effective alternative for self-administration. Nonetheless, limitations with SCIT include the need for specialist supervision and the risk of systemic side-effects, particularly in asthmatics. For sublingual therapy there is a restricted spectrum of available vaccines and ensuring adherence to treatment may be a particular problem. Whereas modified allergens and virus like particles as adjuvants have shown early promise, use of alternative routes such as intradermal, epicutaneous and intralymphatic immunotherapy and peptide therapy targeting selected T cell or B cell epitopes have so far been unsuccessful in phase 3 trials. There remains a clear need to improve immunotherapy to achieve greater efficacy, safety, and adherence to therapy and to achieve more durable long-term tolerance.

Monoclonal antibodies that selectively target IgE and type 2 immunity have proved highly effective and corticosteroid-sparing in asthma, eczema, and other Th2-driven diseases. There is no evidence that these approaches, when used as single therapies have a disease-modifying effect. Nonetheless, there is a clear rationale and growing interest in using these monoclonal antibodies in combination with allergen immunotherapy.

Combination therapy with AIT and anti-IgE is to date the most promising therapeutic strategy, not only enhancing AIT's safety and tolerability but also providing additional evidence of efficacy compared to AIT alone. When combined with AIT, anti-IL-4 receptor offers a reduction in side effects and an improved immunological profile. However, its impact on short-term efficacy of AIT appears limited. Whether or not targeting the IL-4 receptor alpha could have an impact on long-term tolerance remains to be determined. Targeting epithelial cytokines in combination with AIT is an alternative option. In a recent randomised controlled trial, one year's treatment with subcutaneous cat dander immunotherapy administered along with anti-TSLP demonstrated enhanced AIT efficacy in response to nasal allergen provocation with suppression of symptom scores and immune responses at one year that persisted for one year after discontinuation of therapy compared to AIT alone. Further long-term studies are needed to evaluate the sustained benefits and safety profiles of combination strategies.