Molecular Allergen Component Resolved Diagnosis to Decide Immunotherapy (CRD-AIT)

Molecular Allergen Based Diagnosis Impact on Clinical Efficacy of Aeroallergen Immunotherapy- a Pragmatic Randomized Clinical Trial

Allergen immunotherapy (AIT) is used for the control of allergic diseases that are not completely responsive to avoidance strategies and/or pharmacotherapy. It is also considered the main treatment with the potential to modify allergic disease evolution. It's efficacy and safety in allergic rhinitis and asthma is supported by large systematic reviews and is recommended as a cornerstone treatment option in allergic disease. Molecular based allergy diagnosis has greatly evolved and the knowledge of molecular allergen sensitization pattern has been used to better define the allergen extract composition of AIT. However, uncertainty remains if this strategy is related to an increase of efficacy. Regulation of allergen extracts for allergen immunotherapy are currently underway in Europe, but there is still lack of standardization of relevant allergens and important differences are seen between allergenic contents. Therefore, we aim to evaluate, in a real-life setting, the impact of using molecular-based diagnosis versus standard diagnostic tools in the efficacy of aeroallergen immunotherapy, using a pragmatic randomized controlled trial design and also to address the impact of the discrepancy between individual aeroallergen sensitization profiles and the major allergen molecular content of aeroallergen immunotherapy.

Patients followed in the allergy clinic with indication for allergen immunotherapy using only standard diagnosis.

Patients followed in the allergy clinic with indication for allergen immunotherapy decided with standard diagnostic tools and molecular based diagnosis.

Physicians in this group will have access to allergen molecular component sensitization profile, using ImmunoCAP ISAC E112i and to all standard diagnostic tolls

Physicians will only have access to standard diagnostic tools namely skin prick tests and sIgE sensitization (not molecular IgE) and clinical history.

Differences, in the mean change at 52 weeks, of CSMS between groups that were treated with AIT in the component resolved diagnosis versus standard diagnosis groups. CSMS is the sum of the daily symptom score (dSS, score 0 to 3) plus daily medication score (dMS; score 0 to 6)

Difference, in the mean change at 24 weeks, of CSMS between groups were treated with AIT in the component resolved diagnosis versus standard diagnosis groups.

Difference between groups(control vs intervention) in the mean change at 52 weeks, in the psychometric response scale. This scale is used to assess rhinoconjunctivitis discomfort and its impacts on symptom severity and need of treatment.

Difference between groups(control vs intervention) in the mean change at 52 weeks, in the psychometric response scale. This scale is used to assess rhinoconjunctivitis discomfort and its impacts on symptom severity and need of treatment.

Differences between groups (control vs intervention) in the mean change at 52 weeks in the scores obtained on the self-administered Portuguese validated questionnaire that assess symptoms and control of both allergic rhinitis and asthma in the previous 4 weeks. The final score ranges from 0 to 30, with scores over 24 indicating good control of asthma and allergic rhinitis, a four-point changes will be considered the minimal important difference

Differences between groups (control vs intervention) in the mean change at 24 weeks in the scores obtained on the self-administered Portuguese validated questionnaire that assess symptoms and control of both allergic rhinitis and asthma in the previous 4 weeks. The final score ranges from 0 to 30, with scores over 24 indicating good control of asthma and allergic rhinitis, a four-point changes will be considered the minimal important difference.

Differences between control and intervention group of change in the self-report questionnaire regarding asthma symtoms that includes 5 items assessing each of the following for the previous 4 weeks. ACT score ranges from 5 (poor control of asthma) to 25 (complete control of asthma)

Differences between control and intervention group of change in the self-report questionnaire regarding asthma symtoms that includes 5 items assessing each of the following for the previous 4 weeks. ACT score ranges from 5 (poor control of asthma) to 25 (complete control of asthma)

Difference between groups regarding self-administered version of Rhinoconjunctivitis Quality of Life Questionnaire which is validated in Portuguese for patients over 12 years at 52 weeks. A change greater than 0.5 will be considered a critically clinically significant difference

Differences between groups regarding the self-administered version of Rhinoconjunctivitis Quality of Life Questionnaire which is validated in Portuguese for patients over 12 years at 24 weeks. A change greater than 0.5 will be considered a critically clinically significant difference

Differences between intervention and control groups in the self-administered questionnaire with 16 questions distributed in 4 dimensions: perception of effectiveness, activities and environment, cost-benefit balance and general satisfaction at 52 weeks

Differences in the self-administered questionnaire with 16 questions distributed in 4 dimensions: perception of effectiveness, activities and environment, cost-benefit balance and general satisfaction at 24 weeks

Direct and indirect healthcare related costs will be assessed in each of the groups before and after treatment and compared

Inclusion Criteria: Individuals with medical indication for aeroallergen immunotherapy(AIT) for allergic rhinoconjunctivitis or asthma, accordingly to the AIT guidelines; Over 5 years of age; Evidence of IgE-sensitization (positive skin prick tests and / or serum specific-IgE) Patients have indication to AIT to house dust mites and/or grass pollen, association with other allergens is not an exclusion criteria Exclusion Criteria: Previously performed allergen immunotherapy Need the use of molecular allergen diagnosis to decide treatment and diagnostic strategy

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