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