Efficacy of House Dust Mite Sublingual Tablet in the Treatment of Allergic Rhinoconjunctivitis: A Randomized Trial in a Pediatric Population

Abstract

To investigate the efficacy, safety, and immunologic response of standardized sublingual house dust mite (HDM) tablets in Japanese pediatric patients.Included in the study were patients ≥5 and ≤16 years of age with allergic rhinitis symptoms for ≥2 years, a score of ≥3 on quantitative analysis of specific immunoglobulin E antibody to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae antigens, positive nasal provocation test result for HDM, and Rhinitis Total Symptom Score ≥6 points per day for 7 days before randomization. Those with symptoms from other allergens, mild persistent or more-severe asthma, or inhaled corticosteroid use were excluded.This multicenter, double-blind, randomized placebo-controlled trial was conducted at 51 Japanese medical institutions from October 2015 to December 2016. Subjects were randomly assigned 1:1 to placebo or HDM tablets with an index of reactivity of 300 daily for 52 weeks. Symptoms and rescue medication use were recorded daily in a patient diary. The primary end point was the average adjusted symptom score for week 48 to 52, derived from daily Rhinitis Total Symptom Scores and adjusted for rescue medication use.Of 438 patients who were randomly assigned, 193 patients in the treatment group and 210 patients in the placebo group completed the study. The average adjusted symptom score was significantly lower in the treatment group compared with placebo (6.32 vs 7.27, P = .0005), with a least-squares mean difference of −13.1%. Improvement was seen at weeks 8 to 10 and was maintained throughout. Nasal Individual Symptom Scores were significantly lower in the treatment group, whereas Average Rescue Medication Scores and Ocular Individual Symptom Scores were not. Specific immunoglobulin E antibodies to HDM nearly doubled, whereas specific immunoglobulin G4 antibodies approximately tripled in the treatment group. Mild or moderate adverse events (oral pruritus, mouth edema, throat irritation, ear pruritus, and mouth swelling) occurred in most patients (96.8% of treated patients, 94.5% of placebo patients), typically from days 1 to 14. Two serious adverse events were reported in the placebo group and 6 were reported in the treatment group, leading to drug discontinuation in 1 patient with pseudocroup. Overall, 8% of randomly assigned patients discontinued the study, mostly because of adverse effects. There were no deaths or anaphylactic events requiring intramuscular epinephrine.This study demonstrates efficacy and safety of HDM sublingual tablets in pediatric patients with perennial allergic rhinitis due to HDM allergy. Treatment conferred significant and sustained improvement in symptom scores, with a similar immunologic response and safety profile, as previously shown in older age groups.This study is limited by a lack of objective outcomes, such as peak nasal inspiratory flow or nasal provocation tests. The investigators also excluded patients with persistent asthma and symptomatic rhinitis due to other allergens, which commonly occur in patients with HDM-triggered rhinitis. Although modest improvement in symptoms was shown, daily therapy over a 52-week treatment course may be impractical for pediatric patients. One likely goal of HDM immunotherapy may be to decrease use of other medications, but this was not seen in the current study. Further studies are needed in this population to assess optimal treatment duration and whether treatment confers sustained benefit after drug discontinuation.