In a letter published recently in the Journal of Allergy and Clinical Immunology, Immune Tolerance Network (ITN) investigators describe the experience of the ITN’s GPAC study (Immunoprophylaxis of Allergic Disease) that aimed to test whether early intervention with a form of oral immunotherapy in at-risk young children could prevent the development of asthma. Evidence suggests that environmental exposure to allergens early on in life via inhalation and mucosal exposure can induce regulatory (vs. inflammatory) responses towards those allergens. The aim of this study was to test the ability of a sublingual allergen mixture (compared to placebo) to enhance mucosal exposure to certain aeroallergens in very young children at high risk for allergy, possibly arresting the development of inflammatory responses and preventing the onset of allergic disease.
One of the challenges with administering sublingual immunotherapy in such young children (aged 12-30 months) is their ability to hold the allergen mixture underneath the tongue for the estimated 2-3 minutes necessary for mucosal penetration and immune recognition. To assess this, the study incorporated an interim 12-month assessment in a portion of the planned subjects to gauge whether the sublingual immunotherapy had been processed and recognized by the immune system; without proper recognition, the investigators reasoned, prevention or tolerance is unlikely. The assessment revealed that children receiving the allergen mixture showed no differences in relevant immunological parameters compared to the placebo group, suggesting allergen exposure below the threshold for immune system recognition. Enrollment was stopped, truncating the sample size without proper powering to evaluate endpoints.
This study underscores the challenges in using sublingual allergen drops in very young children, and suggests the need for improved procedures to achieve better mucosal allergen delivery if targeting prevention in a young cohort. A recent study using a tablet form of sublingual immunotherapy designed to promote prolonged allergen exposure achieved better success in atopic adults compared to past experiences with allergen drops, and could also be considered for prevention in children.