4 The Risk of Severe Treatment Related Adverse Events is Significantly Lower in Children Compared to Adults When Treated With Standardized Timothy Grass Allergy Immunotherapy Tablets

Abstract

BackgroundAllergy immunotherapy tablets (AIT) provides a safer and more convenient alternative to subcutaneous specific immunotherapy treatment. However, severe adverse events occur infrequently. These events are rare and therefore pooled safety data from 1 phase II/III and 6 phase III clinical trials (5 in adults, 2 in children (5–17 years)) with grass AIT (Grazax, Phleum pratense 75,000 SQ-T/2800 BAU, ALK, Denmark) were analysed.MethodAll trials were randomised, double-blind, placebo-controlled multi-centre trials. Subjects suffered from grass pollen induced allergic rhinoconjunctivitis with or without asthma, had positive skin prick test and specific IgE to Phleum pratense. Subjects received once-daily sublingual treatment with grass AIT or placebo for approximately 24 weeks. The 5 adult trials comprised 2095 treated subjects (AIT = 1060, placebo = 1035) and the 2 children trials comprised 597 treated subjects (AIT = 301, placebo = 296). Adverse events were assessed by the investigator as treatment-related (possible or probable) or unlikely related and for seriousness. Application site-related events were defined as adverse events in relation to the oral cavity.ResultsIn the adult trials, 71% of AIT-treated subjects reported treatment-related adverse events compared to 24% for placebo. In the children trials the corresponding numbers were 63% for AIT and 27% for placebo. Of the AIT-treated subjects 2 children (0.7%) and 32 adults (3.0%) experienced severe treatment-related events. The odds for severe events was 4.7 times lower in children compared to adults (odds-ratio with 95% CI, 0.22 [0.025-0.85], P = 0.019). Both AIT-treated children (0.7%) and 18 (1.7%) of the AIT-treated adults experienced severe treatment-related events that were application site-related. The odds for having severe related application site adverse events was 2.6 times lower in children compared to adults (odds-ratio with 95% CI, 0.39 [0.04-1.63], P = 0.27, not statistically significant). No serious treatment-related adverse events were reported.ConclusionThis pooled analysis of over 2000 subjects in 7 clinical trials shows that the risk of experiencing severe treatment-related adverse events was significantly lower in children compared to adults when treated with of Timothy grass allergy immunotherapy tablets. This analysis provides evidence that Timothy grass AIT is an important and safe immunotherapy treatment option in children with grass pollen induced rhinoconjunctivitis.