AIT effectiveness on asthma progression and onset of asthma in
children and adolescents
The progression of asthma was analysed for asthmatic children and
adolescents at baseline. With 16.3%, significantly more patients
treated with MCT®-associated allergoids did not
receive prescriptions for symptomatic asthma medication in the follow up
period vs. control group (p = 0.037). Significant differences were also
shown for the treatment group of allergoid 2 (15.0%,
p < 0.001) and allergoid 3 (11.6%, p < 0.001) and
therefore for the entire AIT treatment group (13.8%,
p < 0.001, see Figure 3b).
In addition, the prescriptions of symptomatic asthma medication in the
MCT®-associated allergoid treatment group were
significantly reduced by 33.7% in the follow-up vs. baseline and
control group (p = 0.016). These effects could also be demonstrated for
the allergoid 2, allergoid 3 and the entire AIT treatment group (22.8%,
25.7%, 24.7%, p < 0.001, see Table 2).
Onset of asthma was analysed for non-asthmatic children and adolescents
at baseline. The probability of asthma medication onset during follow-up
was significantly reduced for children and adolescents treated within
the AIT group compared to controls (OR: 0.74; p = 0.02, see Figure 4a).
The probability of not being prescribed symptomatic asthma medication
was significantly greater for children and adolescents treated with AIT
compared to the control group (see Figure 4c).
Discussion
The TARGET study demonstrates that grass or tree pollen AIT is
associated with significantly reduced AR progression, i.e. less
symptomatic medication prescriptions in the total AIT group and
different allergoid SCIT groups. These results are in line with the
results of other RWE studies published by Wahn et al and Vogelberg et al
. The beneficial effect was demonstrated for
MCT®-associated SCIT allergoid with a higher
percentage of patients without AR medication prescription in comparison
to the control group. The percentage of patients without AR medication
prescription is in line with other RWE studies . In addition, a
significant reduction of AR medication prescription in the follow-up vs.
baseline and control group was observed for the
MCT®-associated allergoid. Beneficial effect was also
observed for allergoid 2 and 3.
The TARGET study also showed a significant decrease in the probability
of requiring anti-asthmatic medication and amount of anti-asthmatic
mediation prescribed during follow up. This beneficial effect was also
observed for the different analysed AIT products including a higher
percentage of patients without asthma medication in comparison to the
control group. As for AR medication, the control group also requires
less anti-asthmatic medication. The proportion of asthmatic
children/adolescents not requiring anti-asthmatic medication during
follow-up is even greater compared to adults. Again, this effect was
also seen for the AIT subgroup analysis. In terms of the additional
reduction in asthma medication during follow-up vs pre-index compared to
the control group, the TARGET study revealed a reduction of 29.1%
points for the total AIT population. Wahn et al. reported a reduction of
32.0% points overseeing a shorter follow-up period of up to 6 years.
The Kaplan-Meier curves for AIT patients and patients without AIT are
very close in the first five years of follow-up, however, afterwards the
probability of asthma free survival is greater for AIT patients compared
to control patients. Importantly, the beneficial effect of an AIT on the
occurrence of asthma was statistically significant overall as well as
for adults and children/adolescents which is in contrast to the study by
Wahn et al. This might be due to the higher proportion of children and
adolescents in the TARGET study (~45% vs
~20%) as it has been proposed that onset of asthma can
be best prevented starting therapy early in childhood and adolescence .
The European Academy of Allergy and Clinical Immunology (EAACI)
recommend AIT for children and adolescents in order to prevent asthma .
Further, another retrospective RWE LRx database study by Devillier et
al. point out the consistent long-term benefits of an AIT in patients
with AR with or without associated asthma in terms of slower progression
of AR and asthma medication intake, and reduced risk of new‐onset asthma
medication use, mirroring the efficacy findings in RCTs in the
real-world setting . The findings of the TARGET study are supported by a
recent retrospective cohort study by Fritzsching et al., REACT, using
claims data of a German health insurance fund database . Fritzsching et
al. also found AIT patients to be associated with greater reductions in
AR and asthma prescriptions and a reduction in asthma treatment compared
to control subjects. It must be considered that real-world studies
should not be directly compared due to different in- and exclusion
criteria, data source, matching of patients and further aspects of
differing study design.
The present real‐world findings add to the current body of clinical
evidence extending existing RCT evidence for AIT. Becker et al.
performed a meta-analysis on RCTs recently showing a significant
improvement of allergic symptoms and reduction in medication use in
patients treated with MCT®-associated allergoids .
Showing a reduction in AR and asthma medication prescription of 24.2%
and 35.6% compared to control group after SCIT with
MCT®-associated allergoids, the results of the TARGET
study are highly valuable data to complement the efficacy data of
MCT®-associated SCIT allergoids.
This RWE study had several limitations. Clinical information had to be
obtained via proxies like for AR diagnosis by prescription of
symptomatic AR medication . Some patients with AR might have not been
detected, because a large proportion of AR medication is available
over‐the counter. Furthermore, from 2017 onwards some intranasal
corticosteroids were not reimbursed. However, for children up to the age
of 12 years non-prescription AR drugs can be prescribed at the expense
of the statutory health insurance funds which should minimize this
effect in this age group. Moreover, all anti-asthmatic medications are
prescription-bound. In total, any such bias should affect both the AIT
and non-AIT control groups equally, thus not impacting the relative
comparisons between the groups.
Importantly, the unmet need for an appraisal of the quality of RWE in
AIT has been addressed by Paoletti et al. who recently initiated a
systematic review of observational studies of AIT to provide an
essential source of real-world data and improve quality in clinical
decision making . RWE will likely prove to be of enormous value to
synthesize evidence from the different sources RCTs and RWE studies, a
position which is already changing with regard to evolving regulatory
opinions, guidance frameworks, and with growing recognition of the value
of using RWE that is acceptable for regulatory decision‐making . The FDA
and EMA is already developing guidance that defines how regulators
consider RWE in their decision-making - both for new and existing
approvals .
The main strengths of this study are that it was conducted in a
real‐world, large and inclusive patient cohort, with the longest follow
up period (after AIT completion) shown in AIT RWE studies (up to 9.5
years, Ø 6.3 years). The current study used a stringent patient‐matching
process with at least 58% of eligible patients being matched to
appropriate controls. Each AIT group was matched separately to their
controls ensuring high data quality and a good comparability of the
study cohorts with their controls. This reduced confounding, avoided
possible bias from intergroup differences and ensured robustness of
findings.
Conclusions
RWE studies are playing an increasingly important role. Health
authorities in US and Europe have recognized the added value of RWE
studies. In addition to DBPC studies RWE data increase corroboration by
allowing insights into the therapeutic effectiveness after AIT
completion, especially in children and adolescents.
The TARGET study has the longest
follow-up period (after AIT completion) shown in AIT RWE studies so far
and demonstrates the long-term benefit of pollen (grasses or trees)
allergoid SCIT including MCT®-associated allergoids on
the progression of AR and progression and occurrence of asthma up to 9.5
years of follow-up in clinical practice.
Importantly, also the prevention
of asthma was demonstrated. Results were significant for all patients
(5-65 years) but also for children/adolescents and adults in the
individual analyses. The results of the TARGET study substantiate the
findings of other RWE studies in patients with pollen-induced allergies
and demonstrate the effectiveness of authorized SCIT allergoids
including MCT®–associated allergoids in AR and asthma
under real-world conditions.