Achieving disease modification with food allergy therapies: An international perspective.

Abstract

A disease-modifying therapy aims to alter natural history by delaying or reversing disease progression. This rostrum examines expert opinion regarding the concept of disease modification in food allergy and contextualizes relevant definitions, such as desensitization, sustained unresponsiveness, tolerance, and remission. It evaluates evidence-based disease-modifying effects of current and emerging therapeutic strategies from clinical and immunological to patient-centered perspectives. Evidence from oral, epicutaneous and sublingual immunotherapy demonstrates that desensitization is common and that a subset of patients consistently achieve sustained unresponsiveness or remission after treatment discontinuation. Studies to date have noted that younger age and lower baseline allergen-specific IgE may predict more durable responses, although findings are inconsistent across populations and allergens. Immunologic changes associated with these outcomes include suppression of Type 2 cellular responses, modulation of B-cell compartments and induction of blocking antibodies, but no clear link to a specific clinical state can be claimed. Currently approved biologics enhance protection during active treatment, but have limited evidence for direct disease modification, although they may facilitate tolerance when combined with allergen exposure. Patient-reported outcomes, especially quality of life and self-efficacy remain critical yet underutilized measures of therapeutic benefit. Clinical trial designs face multiple challenges in evaluating long-term disease modification. While the clinical states of desensitization, sustained unresponsiveness, tolerance and remission may involve partial or complete disease modification in food allergy, no consensus definition exists or relevant biomarker has been identified to date. Future work will require harmonized definitions, innovative trial designs and therapies targeting long-lived immunological memory with continued emphasis on patient-centered outcomes and real-world clinical relevance.