Background:
Over the last 50 years the number of patients with allergies has
increased rapidly . Children are affected with a 12-month prevalence of
AR of 8.8% increasing to 15.3% in adolescence .
Allergic rhinitis (AR) commonly
precedes asthma and about 85% of asthma patients also have AR . In
Germany, about 1 million children and adolescents are affected by AR,
about 0.5 million of adolescents by asthma and among adults the 12-month
prevalence of asthma is 6% . The increasing number of adult patients
affected by allergies emphasize the importance of effective and causal,
disease modifying therapies nowadays and in the future.
Allergen immunotherapy (AIT) has
a long-term disease modifying effect as a causal and preventive approach
regarding allergic progression or new sensitizations . As the relative
risk of developing bronchial asthma within less than 10 years is
3.5‑fold higher for patients with AR and the risk of a change from AR to
allergic asthma is greatest for children with hay fever, an early
initiation of AIT for children and adolescents is recommended with focus
on products, for which appropriate effects have been shown . For AIT
several standardized products are available, differentiated by the route
of application as subcutaneous (SCIT) or sublingual immunotherapy
(SLIT).
SCIT allergoids are chemically modified allergens with reduced IgE
binding capacity allowing fast updosing with a good safety profile
demonstrated for children and adults . In addition, SCIT is well
investigated in controlled, intermittent and mild persistent asthma .
The most common adjuvant to strengthen the AIT immune response is
aluminium hydroxide . An alternative adjuvant, microcrystalline tyrosine
(MCT®), shows a favourable safety profile inducing
even less anaphylactic reactions in mice and induces less TH2 related
cytokines which should be suppressed in AIT .
AIT patients should be treated for at least 3 years, SCIT must be
administered by a physician and requires regular visits during the
maintenance phase. Thus, patient adherence is essential for efficacy,
especially in clinical practice routine. In real life, a low level of
compliance and persistence, particularly when using SLIT is observed .
According to the German S2k AIT Guideline, insufficient compliance is a
contraindication to AIT with allergens ).
Double-blind placebo-controlled studies (DBPCSs) are classified as gold
standard evaluating the efficacy of medical treatments, although it has
to be considered that e.g. in SLIT DBPC trials a complete blinding is
not possible . This may have an influence on the placebo effect.
The efficacy and safety has been proven for various SCIT allergoids
preparations including MCT®-associated allergoids in DBPC studies and
meta-analyzes under ideal clinical study conditions .The efficacy of
MCT®-associated SCIT allergoid was demonstrated recently in a
meta-analysis providing strong evidence on the efficacy of SCIT in
pollen allergy-induced allergic rhino conjunctivitis (ARC), showing
significant reduction of allergic symptoms and medication use . In
addition to DBPC studies Real-world evidence (RWE) data increase
corroboration by allowing insights into the therapeutic effectiveness,
especially in children and adolescents, particularly after AIT
completion. RWE studies are playing an increasingly important role.
Health authorities in US and Europe have recognized the added value of
RWE studies and are working on the framework of the ”Real-World Evidence
Program” .
The aim of the ”Tyrosine
Allergoid - Real World Evidence in Germany - Effectiveness in AIT”
(TARGET) study is to demonstrate the long-term benefit of
MCT®-associated allergoid pollen SCIT on AR and asthma
in adults, children and adolescents (5-65 years) in clinical practice
routine.
Methods