Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

Allergen Immunotherapy for the Prevention and Treatment of Asthma.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease-modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease-modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.

Improved quality control of allergen products: Assessing the molecular allergen composition by mass spectrometry.

BACKGROUND: Natural allergen sources contain a variety of allergens, against which allergic subjects have developed individual sensitization profiles. Ideal allergen products for skin prick testing (SPT) and allergen immunotherapy (AIT) should contain the complete set of allergens of the respective allergen sources to cover all sensitization profiles. However, commercially available allergen products were shown to vary regarding their allergen composition. METHODS: The qualitative allergen composition of different SPT and AIT products produced from pollen of grasses, birch, mugwort and from house dust mites was assessed by a consistent high-resolution liquid chromatography-coupled tandem mass spectrometry method (LC-MS/MS). RESULTS: All major, mid-tier and most minor allergens were detected in each of the investigated three batches of SPT and AIT products, demonstrating the completeness of the allergen composition and a high degree of batch-to-batch consistency. CONCLUSION: This is the first study using a single consistent high-resolution LC-MS/MS method to provide solid data on the qualitative allergen composition of SPT and AIT products manufactured from various common allergen sources. The applied method showed high reliability in qualitative batch-to-batch consistency testing and can be performed fast and with high throughput. High-resolution LC-MS/MS is applicable for process development and quality control to ensure market availability of allergen products corresponding to the composition of the respective natural allergen sources.

The SQ tree sublingual immunotherapy tablet is effective and well tolerated in children-A pivotal phase III trial.

BACKGROUND: Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT-tablet in a paediatric population (5-17 years) with moderate-to-severe AR/C induced by pollen from birch and trees in the birch homologous group. METHODS: Nine hundred and fifty-two subjects were randomized (1:1) to daily treatment with SQ tree SLIT-tablet or placebo for up to 52 weeks and had free access to AR/C symptom-relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS). RESULTS: SQ tree SLIT-tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment-related adverse events were mild or moderate local administration site reactions. CONCLUSION: This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT-tablet in tree pollen-induced AR/C in a paediatric population (5-17 years).

Hot topics in allergen immunotherapy, 2023: Current status and future perspective.

The importance of allergen immunotherapy (AIT) is multifaceted, encompassing both clinical and quality-of-life improvements and cost-effectiveness in the long term. Key mechanisms of allergen tolerance induced by AIT include changes in memory type allergen-specific T- and B-cell responses towards a regulatory phenotype with decreased Type 2 responses, suppression of allergen-specific IgE and increased IgG1 and IgG4, decreased mast cell and eosinophil numbers in allergic tissues and increased activation thresholds. The potential of novel patient enrolment strategies for AIT is taking into account recent advances in biomarkers discoveries, molecular allergy diagnostics and mobile health applications contributing to a personalized approach enhancement that can increase AIT efficacy and compliance. Artificial intelligence can help manage and interpret complex and heterogeneous data, including big data from omics and non-omics research, potentially predict disease subtypes, identify biomarkers and monitor patient responses to AIT. Novel AIT preparations, such as synthetic compounds, innovative carrier systems and adjuvants, are also of great promise. Advances in clinical trial models, including adaptive, complex and hybrid designs as well as real-world evidence, allow more flexibility and cost reduction. The analyses of AIT cost-effectiveness show a clear long-term advantage compared to pharmacotherapy. Important research questions, such as defining clinical endpoints, biomarkers of patient selection and efficacy, mechanisms and the modulation of the placebo effect and alternatives to conventional field trials, including allergen exposure chamber studies are still to be elucidated. This review demonstrates that AIT is still in its growth phase and shows immense development prospects.

Telemedicine with special focus on allergic diseases and asthma-Status 2022: An EAACI position paper.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID-19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face-to-face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

[Update on asthma 2024 - what the ENT specialist needs to know]. / Aktuelles zum Asthma 2024 ­ was der HNO-Arzt wissen muss.

The lifetime prevalence of 8.6% of asthma in Germany reflects the high medical and socioeconomic impact of the disease. Asthma treatment goals have changed during the last decades: from symptom control to symptom prevention, with highly effective, disease-modifying anti-asthmatic drugs (DMAADs) aiming at asthma remission. In order to achieve this goal, phenotyping of patients (including an evaluation of allergies and type 2 biomarkers) is crucial for personalized treatment. The identification and effective treatment of concomitant diseases, such as allergic rhinitis or chronic rhinosinusitis with nasal polyps (CRSwNP), plays a major role for successful treatment. This underlines the importance of interdisciplinary collaboration of otolaryngologists and respiratory physicians in the management of patients with asthma. This CME article informs the reader about current guidelines on the diagnosis and treatment of asthma, focusing on clinically relevant recommendations for ENT physicians.

Adherence and persistence in allergen immunotherapy (APAIT): A reporting checklist for retrospective studies.

BACKGROUND: Adherence is essential for the long-term efficacy of allergen immunotherapy (AIT) and has been evaluated in numerous retrospective studies. However, there are no published guidelines for best practice in measuring and reporting adherence or persistence to AIT, which has resulted in substantial heterogeneity among existing studies. The 'adherence and persistence in AIT (APAIT)' checklist has been developed to guide the reporting, design and interpretation of retrospective studies that evaluate adherence or persistence to AIT in clinical practice. METHODS: Five existing checklists, focussing on study protocol design, the use of retrospective databases/patient registries, and the appraisal and reporting of observational studies, were identified and merged. Relevant items were selected and tailored to be specific to AIT. The content of the checklist was discussed by 11 experts from Europe, the United States and Canada, representing allergy, healthcare and life sciences, and health technology appraisal. RESULTS: The APAIT checklist presents a set of items that should either be included or at least considered, when reporting retrospective studies that assess adherence or persistence to AIT. Items are organized into four categories comprising study objective, design and methods, data analysis, and results and discussion. The checklist highlights the need for clarity and transparency in reporting and emphasizes the importance of considering potential sources of bias in retrospective studies evaluating adherence or persistence to AIT. CONCLUSIONS: The APAIT checklist provides a pragmatic guide for reporting retrospective adherence and persistence studies in AIT. Importantly, it identifies potential sources of bias and discusses how these influence outcomes.

Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper.

INTRODUCTION: In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. METHODS: The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. RESULTS: Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. CONCLUSION: This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT.

European Academy of Allergy and Clinical Immunology position paper on endoscopic scoring of nasal polyposis.

Nasal endoscopy is not only used for the diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP), but also for monitoring the response to therapy playing an important role in both daily practice and research. In contrast to patient-reported outcomes, endoscopic nasal polyp scoring by independent blinded readers is an objective measurement, not influenced by the placebo effect. It is safer and cheaper compared with computed tomography imaging and therefore, better suited for regular assessments of the extent of the disease. Since the early 90s, a variety of endoscopic staging methods have been proposed and used in clinical research, making it hard to compare results from different studies. This paper resulted from a task force with experts in the field of CRSwNP, originated by the Ear, Nose and Throat section of the European Academy of Allergy and Clinical Immunology and aims to provide a unified endoscopic NP scoring system that can serve as a reference standard for researchers, but also as a useful tool for practitioners involved in the management of CRSwNP.

A practical toolbox for the effective transition of adolescents and young adults with asthma and allergies: An EAACI position paper.

INTRODUCTION: Adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI. AIM: We herein summarize practical resources to support this guideline's implementation in clinical practice. METHODS: For this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality and were pragmatically rated for their evidence-basis and user friendliness. RESULTS: Resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace and wider community. Most resources were in English, web-based and had limited evidence-basis. CONCLUSIONS: This position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care.

Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper.

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study.

INTRODUCTION: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. METHODS: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. RESULTS: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. CONCLUSIONS: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

[Treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with monoclonal antibodies (biologics): S2k guideline of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the German College of General Practitioners and Family Physicians (DEGAM)]. / Therapie der chronischen Rhinosinusitis mit Polyposis nasi (CRScNP) mit monoklonalen Antikörpern (Biologika): S2k-Leitlinie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) und der Deutschen Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM).

Monoclonal antibodies (so-called biologics) can be prescribed for chronic rhinosinusitis with nasal polyps (CRSwNP) within the scope of their market authorization. However, their prescription is limited to severe CRSwNP without disease control, whereby certain requirements must be met. Dupilumab, omalizumab, and mepolizumab have currently gained market authorization, with adequate evidence for their efficacy and safety available in the literature. It can be assumed that other biologics will be approved for this indication in the future. The severity of disease and the efficacy of treatment should be assessed objectively and subjectively before treatment initiation and after an appropriate duration, respectively. The documentation sheet proposed in this guideline chapter can be used for the assessments. In the presence of relative contraindications, a treatment should only be initiated after differentiated consideration by an experienced physician in the sense of a case-by-case decision. In summary, this guideline chapter aims to contribute to high-quality care of adult patients with these therapies in view of the increasing evidence for treatment with these substances and the increasing number of market authorizations of different biologics.

[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

Care with allergen immunotherapy for allergic respiratory diseases in Germany-Predictors and deficits.

BACKGROUND: Allergen immunotherapy (AIT) represents the only possibility of causal therapy for allergic respiratory diseases. Although the prevailing high prevalence of allergic diseases and restrictions in the daily lives of patients, AIT is offered to a suboptimal number of patients in Germany. METHODS: Insured patients with documented allergic respiratory disease of one of the largest statutory health insurances in Germany, 'DAK-Gesundheit', were contacted by postal mail and asked to participate in the study. In case of written consent, primary and secondary data of patients were collected and analysed. Patient characteristics, predictors of being offered AIT, predictors of performing AIT and guideline-compliant care were analysed. RESULTS: 2505 subjects were included in the VerSITA study. Allergy to tree pollen and native speaking were identified as predictors, which increase the probability of being offered AIT. The probability was significantly decreased by the characteristics allergic rhinitis only, allergic asthma only, age in years, non-German citizenship, no graduation and lower secondary qualification. Significant positive predictors for an AIT to be actually performed were: Allergy to tree pollen and male sex. Predictors that decrease the likelihood that AIT is performed were: only allergic asthma, current smoker, former smoker, age and non-German citizenship. Furthermore, it was possible to identify characteristics in which guideline-compliant patients differed significantly from the rest of the study population. CONCLUSIONS: Based on statutory health insurance data and patient survey data, the VerSITA study provides a broad and in-depth overview of the care situation with regard to AIT in Germany and identifies deficits.