Discussion
These results from a pooled safety analysis of clinical trials with 929
adults and adolescents with allergic rhinitis and/or conjunctivitis
induced by birch pollen, revealed no major safety concerns in relation
to daily at-home use of the SQ tree SLIT-tablet. Thus, the safety
profile supports daily at-home sublingual administration once the first
dose is tolerated when administered under medical supervision: Most
application-site reactions were local reactions of the mouth, throat,
and ear and were generally occurring early in treatment and were
transient, and self-resolving. Also, no anaphylactic reactions or
IMP-related SAEs were reported for the subjects.
The results confirm previous safety findings with other SQ sublingual
immunotherapy tablets. A grass SLIT-tablet showed a similar safety
profile dominated by local allergic applications-site reactions
primarily in the oral cavity and throat of mild or moderate severity
with an early onset and transient and self-resolving
AEs16-17. Also, the safety profile of a house dust
mite SLIT-tablet revealed transient, mild local allergic reactions
representing the most commonly occurring adverse
reactions18.
Around 70 percent of individuals with birch pollen allergy develop
pollen food syndrome (PFS)1, and in the present study
64% of subjects had PFS. This PFS subpopulation could be expected to be
more challenged in relation to their allergic disease, and the safety
profile may therefore differ compared with a subpopulation with no
PFS19. In the present data, subjects with PFS tended
to experience more AEs regardless of treatment than subjects without
PFS, especially oral pruritus. Of subjects treated with 12 SQ-Bet, oral
pruritus was reported by almost half of the subjects with PFS (45%) and
was thus far more frequent than in subjects without PFS (29%). This
difference was not seen in relation to severity. This high reporting of
oral pruritus is in accordance with what is usually seen in relation to
PFS19.
The present data suggest no increased risk of asthma events among all
subjects treated with 12 SQ-Bet. In addition, no acute asthma worsening
was seen in subjects with a medical history of asthma. This is in line
with the general safety profile of sublingual immunotherapy revealing no
greater risk for adverse reactions in well controlled
asthma7. However, in the studied population, subjects
with severe and/or uncontrolled asthma were excluded, and the safety
profile of 12 SQ-Bet remains to be investigated in this subpopulation.
Patients with birch pollen allergy may show urticaria or worsening of
atopic dermatitis when exposed to birch pollen20-21.
In the present pooled safety analysis, only one event of worsening of
atopic dermatitis was reported, however we saw more events of urticaria
in the group treated with 12 SQ-Bet compared with placebo. Contact
urticaria following direct contact to allergen containing SLIT tablets
are to be interpreted like PFS developing in the mouth. Only one
subject in the active group developed urticaria at sites distant from
the local exposure. This may or may not be related to the systemic
administration of 12 SQ-Bet, since similar events were reported in the
placebo group.
EoE is highly associated with PFS and one study has found that around
half of EoE patients had symptomatic PFS.22, 23 In the
present study, more than 60% of the subjects had PFS, but the incidence
of EoE in populations with PFS has to our knowledge not been
investigated. No cases of EoE were found during treatment, however the
length of the studies including 6-9.5 months of treatment might not have
been sufficient to detect possible EoE cases.
The studies included in the present pooled safety analysis were all
short-term studies conducted during one pollen season. No long-term
studies have been conducted with the SQ tree SLIT-tablet, however
long-term studies with the grass SLIT-tablet has revealed a favourable
safety profile and long-term treatment effect17,24.