Safety in special groups
No events of anaphylactic reactions or eosinophilic esophagitis (EoE)
were reported. A subgroup analysis did not show any major differences in
the risk of experiencing first moderate to severe IMP-related AEs across
subgroups including age, asthma history, sensitisation, IgE level and
PFS status (Figure 4). Across all subgroups, hazard ratios were less
than 1, i.e. there was an increased risk of IMP-related AEs in the
active treatment group compared with placebo as expected. The subgroup
analysis did not show any major differences in the risk of experiencing
a moderate or severe IMP-related AE across subgroups, including age
(adolescents versus adults, p=0.487), sensitisation status (mono- versus
poly-sensitisation, p=0.571), birch IgE class (class 2-3 versus 4-6,
p=0.573), asthma status (asthma versus no-asthma, p=0.077) and PFS
status (PFS versus no-PFS, p=0.589).
PFS: At baseline, 296 (63%) and 296 (65%) of subjects treated
with 12 SQ-Bet and placebo respectively reported to have PFS. After
treatment, 9 subjects reported AEs of PFS: 7 subjects treated with 12
SQ-Bet (including 4 AEs of worsening of PFS) and 2 subjects treated with
placebo (including 1 AE of worsening of PFS). All AEs were assessed as
IMP-related when treated with 12 SQ-Bet and 1 was assessed as
IMP-related with placebo. A larger proportion of subjects with PFS
reported AEs compared with those without PFS. This was observed for both
treatments: 89% of subjects with PFS and 80% without PFS experienced
AEs with 12 SQ-Bet and 67% versus 56% experienced AEs with placebo.
Likewise, of those treated with 12 SQ-Bet, oral pruritus was reported by
45% of subjects with PFS and by 29% of subject with no PFS. No major
differences between subjects with and without PFS were seen for severity
of AEs. A greater proportion of subjects had IMP interruptions in the
PFS subgroup (19%) compared with subjects without PFS (7%).
Asthma : The 12 SQ-Bet treatment did not seem to induce an
increased risk of asthma events. In total, 18 AEs of asthma were
reported (7 in 7 subjects treated with 12 SQ-Bet and 11 AEs in 10
subjects treated with placebo). These included 6 AEs of asthma
exacerbation: 2 in 2 subjects treated with 12 SQ-Bet and 4 in 3 subjects
on placebo. The majority of asthma AEs were mild or moderate in severity
and assessed as unlikely related to IMP.
For subjects treated with 12 SQ-Bet, the proportion of subjects with
asthma who reported any severe IMP-related AEs was 7% compared with 3%
for subjects without asthma (Figure 3B).
Slightly more adolescents with asthma tended to experience AEs than
adolescents without asthma (85% versus 79%), and these AEs were mild
in severity. However, these data should be interpreted with caution as
only 13 adolescent subjects with asthma participated in the clinical
phase-II/III trial programme.
Eczema : Only one subject reported eczema. This was worsening of a
pre-existing eczema (atopic dermatitis) in a subject treated with 12 SQ
Bet.
Urticaria related to the IMP was reported by 6 subjects treated
with 12 SQ Bet and 4 treated with placebo. The 6 subjects treated with
12 SQ Bet experienced contact urticaria at the administration site (2
subjects reported lip urticaria and 1 subject reported local urticaria),
urticaria at the hand (1 subject), urticaria in several places of the
body (1 subject reported urticaria on the neck after 3 days and on the
chest and upper arm after 212 days) and for 1 subject no details were
specified. 6 subjects in the placebo group also reported urticaria. In 4
of the subjects the events (5 events) were assessed as possibly related
to the treatment despite the subject never being treated with the tree
SLIT-tablet. The events included 4 local reactions and 1 with
unspecified location. In the remaining 2 subjects, urticaria was
assessed as unlikely related to the tree SLIT-tablet.
This suggests either a systemic urticaria or a local urticaria resulting
from touching the SLIT-tablet. None of the urticaria events were severe
or lead to discontinuation.