Dose-Dependent Immunological Responses after a 6-Month Course of Sublingual House Dust Mite Immunotherapy in Patients with Allergic Rhinitis.

Abstract

House dust mite (HDM) immunotherapy has proven efficacy in treating allergic rhinitis (AR) symptoms. This trial evaluated the dose-response relationship of SLIToneULTRA® HDM mix based on immunological parameters and safety in subjects with moderate-to-severe HDM AR not controlled by symptomatic medication. A randomized, parallel-group, open-label, clinical trial compared 50/150/300 standard reactivity unit (SRU) doses of SLIToneULTRA® HDM mix for 6 months. Subjects had moderate-to-severe HDM AR, positive skin prick and IgE against Dermatophagoides pteronyssinus/Dermatophagoides farinae (DP/DF). The primary end point was change from baseline in the IgE-blocking factor against DP after 6 months. Secondary end points measured changes in the IgE-blocking factor for DP at 3 months and for DF at 3 and 6 months, and in IgG4 and specific IgE to DP/DF after 3 and 6 months. Tolerability was assessed through the evaluation of all adverse events (AEs). A total of 219 subjects were randomized and 196 completed the trial. Dose effect was significant on DP IgE-BF after 6 months (p = 0.018). The change in the DP IgE-blocking factor at a 300-SRU dose was higher than at other doses after 3 (p = 0.008) and 6 (p = 0005) months of treatment. Similar changes were observed for IgG4 and allergen-specific IgE. The number of AEs increased with the dose and were mild-to-moderate, with no severe treatment-related AEs reported. The most frequent AEs were oral/tongue pruritus, mouth oedema and abdominal upper pain. Data showed a dose-response for immunological markers and safety with a better immunological response for 300 SRU. The highest dose (300 SRU daily) was considered as the optimal maintenance dose.