Immunotherapy With the SQ Tree SLIT-tablet in Adults and Adolescents With Allergic Rhinoconjunctivitis.

PURPOSE: The SQ tree sublingual immunotherapy (SLIT)-tablet containing allergen extracts with the major allergen Bet v 1 from birch pollen is currently being developed for the treatment of tree pollen-induced allergic rhinitis/conjunctivitis with or without asthma. The aim of this Phase II trial was to investigate the dose-related efficacy and safety of the SQ tree SLIT-tablet. METHODS: This study was a randomized, parallel-group, double-blind, placebo-controlled, multi-national trial conducted in Europe. A total of 637 participants were randomized equally to receive placebo or treatment with the SQ tree SLIT-tablet in doses of 0.5, 1, 2, 4, 7, or 12 development units (DU). Treatment was initiated ~16 weeks before onset of the 2013 birch pollen season (BPS) and was continued throughout the BPS with a total duration of at least 6 months. During the BPS and tree pollen season (TPS), subjects assessed rhinoconjunctivitis symptoms and medication use on a daily basis in an electronic diary; weekly assessments of rhinoconjunctivitis quality of life were also made. FINDINGS: Analysis of the average daily symptom score during the BPS and the TPS showed that the difference between active treatment and placebo was statistically significant for the 7 DU group (BPS, P = 0.02; TPS, P = 0.03), with no clear dose-response relationship. All doses of the SQ tree SLIT-tablet induced changes from baseline in birch-specific IgE and IgG4 that were statistically significant compared with placebo at all time points assessed (P < 0.0001) with a clear dose-response relationship for birch specific IgG4. In general, the SQ tree SLIT-tablet was well tolerated, with the majority of treatment-related adverse events (≥95%) being mild or moderate in severity. The most frequently reported treatment-related adverse events were generally related to the sublingual administration of the tablet (ie, they occurred in the oral cavity). IMPLICATIONS: The results from this trial suggest that the SQ tree SLIT-tablet in doses up to 12 DU has a tolerability profile suitable for at-home administration. The immunomodulatory changes indicate a dose-response relationship, but clinical efficacy parameters were inconclusive, probably due to low pollen counts, emphasizing the importance of pollen exposure for the outcome of a pollen allergy immunotherapy trial. EudraCT no: 2012-000031-59.

Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years.

BACKGROUND: This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abelló A/S, Hørsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy. OBJECTIVE: We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons. METHODS: The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen. Participants were treated with active (n = 189) or placebo (n = 162) tablets for an average of 22 months. All participants were allowed to use symptomatic rescue medication. RESULTS: The primary efficacy analysis showed highly significant mean reductions of 36% in rhinoconjunctivitis symptom score (P < .0001; median reduction, 44%) and 46% in rhinoconjunctivitis medication score (P < .0001; median reduction, 73%) in the active group relative to the placebo group. Mean rhinoconjunctivitis quality of life was 33% better (P < .0001; median, 40%). Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins. The treatment was well tolerated, and adverse events led to withdrawal in less than 1% of participants. There were no serious adverse events related to treatment. CONCLUSION: Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment.