Methods: Pooled analyses of data from subjects with allergic rhinoconjunctivitis enrolled in 7 randomized, double-blind, placebo (PBO)-controlled trials (five phase 2/3 adult; two phase 3 pediatric [ages 5-17 y]) were conducted to evaluate the safety of once-daily standardized Timothy grass allergy immunotherapy tablet (AIT) (oral lyophilisate, Phleum pratense, 2800 BAU, 75,000 SQ-T). Data from adult and pediatric trials were pooled separately. IRB approval and written informed consent from subjects or their legal representation were obtained. Adverse events (AE) were monitored in all trials.
Results: In adult trials, 742/1060 (70%) of AIT subjects and 236/1036 (23%) of PBO subjects reported a treatment-related (TR) AE. In pediatric trials, 188/302 (62%) of AIT subjects and 80/296 (27%) of PBO subjects reported TRAEs. The majority of TRAEs (≥96%) were mild or moderate. The most common TRAEs were oral pruritus, throat irritation, and ear pruritus in adults and oral pruritus, throat irritation, and stomatitis (mild erythema) in children. TRAEs were generally transient local application-site reactions. Local oropharynx AEs rarely led to premature discontinuation. The median days of onset for local AEs were 1-5 days for adults and 1-7.5 days for children. The median number of days local AEs were reported was 3.5-29.5 days for adults and 1.5-16.5 days for children. In adults, there were 5 investigator-assessed systemic allergic reactions (4 mild, 1 moderate) to AIT treatment (0.01 events/subject-treatment year) and 1 possible AIT-related sponsor-assessed systemic reaction (severe diarrhea and mild hives under the tongue). In children, there were no events diagnosed by investigators as systemic allergic reactions, but 4 possible AIT-related systemic reactions were observed based on sponsor assessment (moderate dyspnea and swollen tongue; moderate urticaria; moderate dyspnea with mild pruritus; mild flushing with moderate vomiting).
Conclusions: A pooled safety review of >2000 subjects in 7 trials supports the overall good safety profile of daily Timothy grass AIT in adults and children and did not reveal any new or unexpected safety concerns.