The combination of allergen immunotherapy and biologics for inhalant allergies: Exploring the synergy

Olivieri B, Günaydın FE, Corren J, Senna G, Durham SR. Ann Allergy Asthma Immunol. 2025 Apr;134(4):385-395. doi: 10.1016/j.anai.2024.06.016. 

Abstract

Interplay between AIT and biologics in modulating allergic inflammation. 

The development of monoclonal antibodies that selectively target IgE and type 2 immunity has opened new possibilities in the treatment of allergies. Although they have been used mainly as single therapies found to have efficacy in the management of asthma and other T2-mediated diseases, there is a growing interest in using these monoclonal antibodies in combination with allergen immunotherapy (AIT). AIT has transformed the treatment of allergic diseases by aiming to modify the underlying immune response to allergens rather than just providing temporary symptom relief. Combination strategies involving biologics and AIT exhibit potential in improving short-term efficacy, reducing adverse events, and increasing immunologic tolerance. Anti-IgE emerges as the most promising therapeutic strategy, not only enhancing AIT's safety and tolerability but also providing additional evidence of efficacy compared with AIT alone. Anti–interleukin-4 receptor offers a reduction in adverse effects and an improved immunologic profile when combined with AIT; however, its impact on short-term efficacy seems limited. The combination of cat dander subcutaneous immunotherapy with anti-thymic stromal lymphopoietin was synergistic with enhanced efficacy and altered immune responses that persisted for 1 year after discontinuation compared with AIT alone. Long-term studies are needed to evaluate the sustained benefits and safety profiles of combination strategies. Despite the proven efficacy and safety of AIT, unmet needs call for further research and innovation.

A randomized controlled trial of cat subcutaneous immunotherapy and intravenous tezepelumab. Peak TNSS (0-1 hour) after nasal allergen challenge with cat dander extract revealed a significant difference between SCIT/tezepelumab and SCIT/placebo at week 52 (desensitization end point, *P < .05) and at week 104 (tolerance end point, **P < .01) (cross-sectional comparisons). SCIT, subcutaneous immunotherapy; SLIT, sublingual immunotherapy; TNSS, total nasal symptom score.

Key Messages

• The combination of allergen immunotherapy (AIT) with biologics represents a promising approach in the field of allergy treatment.
• Omalizumab (anti-IgE) enhances the safety and tolerability of AIT while providing additional evidence of efficacy compared with AIT alone.
• Combining dupilumab (anti–interleukin-4 receptor) with AIT for 16 weeks reduces adverse effects and improves the immunologic profile but does not significantly enhance short-term efficacy.
• Cat dander subcutaneous immunotherapy with tezepelumab (anti-thymic stromal lymphopoietin) for 1 year enhances AIT efficacy, with durable suppression of symptom scores and immune response at 1 year after discontinuation compared with subcutaneous immunotherapy alone.
• Further investigation is required to assess the long-term benefits, safety, and optimal dosing schedules of AIT and biologics combination strategy.

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