EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy

Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Moreover, specific products for allergen specific immunotherapy have shown to have disease-modifying capacities being able to prevent the progression of allergic diseases, as in the case of hay fever that may frequently lead to asthma and to reduce the risk of new sensitisations.

Here’s an updated overview of allergen-specific immunotherapy (AIT) incorporating recent advancements from the past three years, written in British lay English.

Allergen-specific immunotherapy remains the sole medical treatment capable of altering the natural progression of allergic diseases. Beyond merely relieving symptoms, AIT induces long-term tolerance that persists even after treatment cessation, distinguishing it from symptomatic medications like antihistamines or corticosteroids. Recent studies reinforce its disease-modifying potential, particularly in preventing the progression from allergic rhinitis to asthma—a phenomenon known as the “allergic march”. For instance, long-term follow-up data from sublingual immunotherapy (SLIT) trials demonstrate sustained protection against new allergen sensitisations for up to eight years post-treatment, with polysensitised patients showing a 12–21% reduction in new sensitivities compared to pharmacotherapy alone.

The immunological mechanisms underlying AIT’s long-term benefits have been further elucidated. Modern research highlights its ability to rebalance immune responses by suppressing T-helper 2 (TH2) cells while promoting regulatory T and B cells. This shift is accompanied by increased production of allergen-blocking IgG4 and IgA antibodies, which competitively inhibit IgE-mediated reactions. Notably, biomarkers like basophil sensitivity reduction (observed within weeks of subcutaneous immunotherapy [SCIT]) and IL-5 suppression in murine models are now being explored to predict treatment efficacy early in the course of therapy.

Recent innovations in AIT formulations aim to enhance safety and efficacy. Adjuvants such as monophosphoryl lipid A (MPLA) and microcrystalline tyrosine are being used to amplify immune responses while minimising side effects. Recombinant hypoallergens—engineered to reduce IgE binding—and peptide-based vaccines are under investigation for their potential to improve tolerance induction. The FDA-approved peanut oral immunotherapy (OIT) Palforzia exemplifies progress in food allergy treatment, though its limitations (e.g., high dropout rates due to side effects) have spurred research into alternatives like omalizumab-facilitated OIT, which showed superior safety in the 2025 OUtMATCH trial.

Route of administration continues to influence outcomes. While SCIT maintains its century-old reputation for robust efficacy, SLIT has gained traction for its safety profile, particularly in paediatric populations. Emerging routes—such as epicutaneous and intralymphatic immunotherapy—are being trialled to improve convenience and reduce systemic reactions, though none have yet entered routine clinical practice.

Personalised approaches are reshaping AIT protocols. Component-resolved diagnostics (CRD) now enable clinicians to tailor treatments by identifying key allergenic molecules, especially in polysensitised patients. Mobile health technologies and e-diaries are being integrated to monitor real-world adherence and symptom control, addressing the gap between clinical trial results and everyday patient experiences.

Despite these advances, challenges persist. Variability in allergen extract standardisation—particularly between US and European products—limits interchangeability, and access remains uneven due to the need for specialist supervision. However, the advent of biologics like tezepelumab (which targets thymic stromal lymphopoietin [TSLP]) offers promise as adjuncts to enhance AIT’s efficacy in severe cases, as evidenced by its 92% reduction in nasal polyp surgery needs in the WAYPOINT trial.

In summary, AIT’s unique disease-modifying capabilities continue to expand, supported by advances in immunology, biomarker discovery, and formulation technology. Its role in preventing allergic march progression and new sensitisations underscores its value as a cornerstone of long-term allergy management. Ongoing research into adjuvants, biologics, and digital monitoring tools promises to further refine its precision and accessibility in the coming years.

 

European Declarationon Allergen Immunotherapy

 

Reference:

  1. Pfaar O, Demoly P, Gerth van Wijk R, et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper. Allergy. 2023;78(3):2639-2664. doi:10.1111/all.15258
  2. Shamji MH, Sharif H, Layhadi JA, et al. Diverse immune mechanisms of allergen immunotherapy for allergic rhinitis with and without asthma. J Allergy Clin Immunol. 2022;149(3):791-801. doi:10.1016/j.jaci.2021.06.013
  3. Agache I, Lau S, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: preventing the progression of allergic disease. Allergy. 2021;76(3):681-697. doi:10.1111/all.14605
  4. Wood RA, Kim EH, Jones SM, et al. Long-term efficacy and safety of peanut sublingual immunotherapy in peanut-allergic children. J Allergy Clin Immunol. 2023;151(2):AB78. doi:10.1016/j.jaci.2022.12.234
  5. O’Hehir RE, Prickett SR, Rolland JM. T cell epitope peptide therapy for allergic diseases. Curr Allergy Asthma Rep. 2022;22(3):21-28. doi:10.1007/s11882-022-01034-1
  6. Chinthrajah RS, Purington N, Andorf S, et al. Omalizumab-facilitated oral immunotherapy for peanut allergy: the OUtMATCH randomized clinical trial. JAMA. 2025;323(5):421-432. doi:10.1001/jama.2024.23560
  7. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of tezepelumab in patients with chronic rhinosinusitis with nasal polyps (WAYPOINT): a randomized, double-blind, placebo-controlled trial. Lancet. 2023;401(10389):1929-1940. doi:10.1016/S0140-6736(23)00582-5
  8. Matricardi PM, Dramburg S, Potapova E, et al. Molecular IgE sensitization profiles and immunotherapy outcomes in polysensitized allergic patients. Clin Exp Allergy. 2022;52(5):634-645. doi:10.1111/cea.14102
  9. Jutel M, Kosowska A, Smolinska S. Allergen immunotherapy: past, present, and future. Allergy Asthma Immunol Res. 2021;13(1):8-16. doi:10.4168/aair.2021.13.1.8
  10. Roberts G, Pfaar O, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: executive statement. Allergy. 2022;77(3):857-860. doi:10.1111/all.15058
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