SQ sublingual immunotherapy tablets for children with allergic rhinitis: A review of phase three trials.

AIM: To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebo-controlled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. METHODS: PubMed searches were conducted and unpublished data were included if necessary. RESULTS: Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials. CONCLUSION: Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease-modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course.

Allergen Release Profiles of Fast-Dissolving Freeze-Dried Orodispersible Sublingual Allergy Immunotherapy Tablets.

Background: Sublingual allergy immunotherapy tablets (SLIT-tablets) provide a well-tolerated and clinically efficacious treatment for allergic disease such as allergic rhinitis and allergic asthma. In SLIT, uptake of allergen by immune-competent cells in the oral mucosa activates the immune system and leads to tolerance toward the sensitizing allergen. The ability to deliver the full allergen content into solution within the recommended sublingual holding time is therefore an essential quality of SLIT-tablets that must be supported by the tablet formulation for all relevant allergen sources. SLIT-tablets based on a fast-dissolving orodispersible freeze-dried formulation (Zydis) are currently available for 5 of the most prevalent allergens: tree (birch and related species from the birch-homologous group), grass, ragweed, Japanese cedar, and house dust mite. Objectives: The purpose of this study was to examine the allergen release properties of three freeze-dried SLIT-tablets containing tree, ragweed, and Japanese cedar extracts, respectively. The correlation between SLIT-tablet allergen release and the level of allergen-specific T-cell activation was examined for the tree SLIT-tablet. Methods: Allergen release kinetics and tablet disintegration times for the 3 freeze-dried SLIT-tablets were examined. For all 3 tablets, the magnitude of solubilized major allergen relative to time in solution was compared to external controls to achieve a measure of the total allergen release. Additional assessments of allergen release occurring after the initial timepoint (15 or 30 seconds in solution) were done independently of external controls by linear regression analyses. For the tree SLIT-tablet, the immunological potency of the released major allergen was assessed at each experimental timepoint by a Bet v-specific T-cell activation assay. Results: All 3 SLIT-tablets disintegrated within 1 second after contact with assay buffer without any detectible residue. Complete release of major allergens (Bet v 1, Amb a 1, and Cry j 1, respectively) was seen at the earliest experimental time points (15 or 30 seconds). For the tree SLIT-tablet, full T-cell activation was achieved at 30 seconds (earliest experimental time point). Conclusions: The freeze-dried SLIT-tablet formulation consistently provides rapid and complete release of allergen from a wide range of species in a standardized in vitro assay. Full release of the SLIT-tablet allergen content within the sublingual holding time is a prerequisite for maximal exposure of allergens to the sublingual mucosa immune system. The freeze-dried SLIT-tablet formulation examined here supports short sublingual holding times and furthermore offers a convenient administration form of allergy immunotherapy.