Statistical methodology
In addition to the pooled population, two other data pools were used in order to investigate the difference between adults and adolescents: One pool including adults (≥ 18 years) and one pool including adolescents (12- < 18 years). The safety analyses were conducted according to the actual treatment that subjects received regardless of randomization.
Demographic (including age and gender) and baseline characteristics was summarised by treatment group. Onset and duration in days were summarised by treatment group and preferred term for most frequent IMP-related AEs (≥ 1% of subjects in the 12 SQ-Bet treatment group). Onset is the time from randomisation to the start of the AE. AEs were summarised in terms of treatment emergent AEs and by causal relation to IMP, severity, seriousness, and AEs leading to discontinuation (treatment emergent AEs and AEs related to IMP respectively).
A graphical overview was presented for the frequencies of the most frequent (≥ 5%) IMP-related AEs for subjects on active treatment in the pooled population by preferred term and worst case severity (i.e. if a subject had more than 1 event, only the highest intensity was used). Likewise, IMP-related AEs in adults and adolescents with and without asthma was presented by treatment group (pooled population) and by-worst case severity (for subjects treated with 12 SQ-Bet only).
To evaluate safety across additional intrinsic factors, an analysis of the differences between treatment groups in risk, calculated as hazard ratio, of experiencing first moderate or severe treatment-related AEs in specific subgroups (age (adolescents/adults), asthma status, IgE level (class 2-3 or class 4-6), sensitisation (mono/poly) and PFS) were performed for the pooled population. The results were presented in a forest plot.