Efficacy and Safety of 5–Grass-Pollen Sublingual Immunotherapy Tablets in Pediatric Allergic Rhinoconjunctivitis

Abstract

Wahn U, Tabar A, Kuna P, et al. J Allergy Clin Immunol. 2009;123(1):160–166PURPOSE OF THE STUDY. To determine the efficacy and safety of a 300-index of reactivity sublingual immunotherapy (SLIT) tablet for children with allergic rhinoconjunctivitis.STUDY POPULATION. Subjects were 278 children (age: 5–14 years) with seasonal grass pollen-induced allergic rhinoconjunctivitis for ≥2 years. Allergy was confirmed by a timothy grass-specific immunoglobulin E (IgE) level of at least class 2 and a wheal diameter of >3 mm in a skin-prick test containing 5 grass pollens included in the SLIT tablet (orchard, meadow, perennial rye, sweet vernal, and timothy grasses). Patients who were sensitized to other allergens present during the grass pollen season, patients who had previously received immunotherapy for grass pollen allergy, and patients with asthma who were receiving medications other than β2-adrenergic receptor agonists were excluded.METHODS. This was a randomized, multicenter, double-blind, placebo-controlled trial conducted in 29 centers in 5 European countries. Patients received daily dosing with either the SLIT tablet or placebo beginning 4 months before and continuing throughout the grass pollen season. The primary outcome was efficacy of treatment, as assessed with the Rhinoconjunctivitis Total Symptom Score, an 18-point scale using 6 common rhinoconjunctivitis symptoms (nasal pruritus, nasal congestion, sneezing, rhinorrhea, ocular pruritus, and watery eyes) scored from 0 to 3 on the basis of severity. Daily symptoms and adverse events were recorded 1 month before and throughout the pollen season. Rescue medication use was scored from 1 to 3 on the basis of the use of antihistamines, nasally administered corticosteroids, or orally administered corticosteroids. Serum levels of IgG4 and IgE specific for grass pollen allergens were measured before and at the end of the study.RESULTS. A total of 278 children received either a SLIT tablet or placebo. The Rhinoconjunctivitis Total Symptom Scores showed benefit corresponding to mean and median improvements across all 6 categories of 28% and 39.3%, respectively, for the SLIT tablet over placebo (P = .01). Significant improvements in rescue medication scores (P = .0064), corresponding to mean and median improvements of 24.1% and 48.7%, respectively, and reductions in symptom scores (P < .038) were seen for the active group, compared with the placebo group. A threefold increase in grass-specific IgG4 levels was seen for the active group, with little change for the placebo group. Changes in grass-specific IgE levels were similar between the groups. Adherence to therapy was similar between the groups (placebo: 95%; active: 94%). A total of 902 treatment-associated adverse events were noted (active: 84.9%; placebo: 82%), with most being mild to moderate in severity. Nine subjects withdrew from the study because of adverse events, including 7 in the treatment group and 2 in the placebo group.CONCLUSIONS. Study data demonstrate that a grass pollen SLIT tablet is effective and safe in decreasing seasonal symptoms in children with allergic rhinoconjunctivitis.REVIEWERS COMMENTS. This study supports data from adult studies showing that SLIT can be an effective therapy for children with allergic rhinoconjunctivitis. In comparison with subcutaneous immunotherapy in this age group, SLIT may be an effective, safe, and convenient option for treating allergic rhinoconjunctivitis.