Timothy specific IgE levels are associated with efficacy and safety of timothy grass sublingual immunotherapy tablet

Background: Regional pollen allergen exposure differences may induce variable sensitization profiles that could affect allergen immunotherapy efficacy and safety.

Objective: To describe sensitization profiles against timothy grass allergen components (Phl p) in North American subjects screened for a timothy grass sublingual immunotherapy (SLIT) tablet trial and evaluate grass SLIT tablet efficacy and safety based on pretreatment Phl p IgE levels.

Methods: Serum-specific IgE was measured post hoc by ImmunoCAP ISAC from subjects screened (N = 1,905) for study P08067 (NCT01385371) conducted in Canada and 5 US regions. Subjects exhibited positivity for timothy grass by skin prick testing and serum IgE. Average total combined symptom plus medication score during the entire pollen season and treatment-related adverse events (TRAEs) were determined in randomized subjects (n = 1,140) by pretreatment Phl p IgE levels (group 1, ≤33rd percentile; group 2, >33rd-67th percentile; group 3, >67th percentile; or undetectable).

Results: Most screened subjects were sensitized to Phl p 1 (73%) and Phl p 5 (51%). The highest mean IgE levels and largest proportions of subjects with positive reactions for Phl p 1 and Phl p 5 were found in Canada and the western United States. Improvements in total combined symptom plus medication score vs placebo by Phl p 5 IgE groups 1 to 3 were 7.7%, 23.9%, and 35.4%, respectively, and 18.7% for subjects with undetectable Phl p 5 IgE. TRAE incidences with the grass SLIT tablet by Phl p 5 IgE groups 1 to 3 were 56.1%, 66.4%, and 74.5%, respectively, and 49.7% in subjects with undetectable Phl p 5 IgE. Similar, but less pronounced, trends for efficacy and TRAEs were observed for Phl p 1 and Phl p 6 IgE.

Conclusion: Sensitization profiles varied by region. Trends toward higher efficacy and increased TRAE incidence in subjects with higher pretreatment Phl p IgE levels were observed.

Trial registry: www.clinicaltrials.gov, identifier NCT01385371.