Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an <scp>EAACI</scp> Position Paper

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Allergen immunotherapy (<jats:styled-content style="fixed-case">AIT</jats:styled-content>) has been thoroughly documented in randomized controlled trials (<jats:styled-content style="fixed-case">RCT</jats:styled-content>s). It is the only immune‐modifying and causal treatment available for patients suffering from <jats:styled-content style="fixed-case">I</jats:styled-content>g<jats:styled-content style="fixed-case">E</jats:styled-content>‐mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on <jats:styled-content style="fixed-case">AIT</jats:styled-content>, for both subcutaneous and sublingual immunotherapy (<jats:styled-content style="fixed-case">SCIT</jats:styled-content> and <jats:styled-content style="fixed-case">SLIT</jats:styled-content>). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>As elaborated by a Task Force (<jats:styled-content style="fixed-case">TF</jats:styled-content>) of the European Academy of Allergy and Clinical Immunology (<jats:styled-content style="fixed-case">EAACI</jats:styled-content>) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different <jats:styled-content style="fixed-case">RCT</jats:styled-content>s and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Based on a thorough literature review, the <jats:styled-content style="fixed-case">TF</jats:styled-content> members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the <jats:styled-content style="fixed-case">TF</jats:styled-content> recommends a homogeneous combined symptom and medication score (<jats:styled-content style="fixed-case">CSMS</jats:styled-content>) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>A standardized and globally harmonized method for analysing the clinical efficacy of <jats:styled-content style="fixed-case">AIT</jats:styled-content> products in <jats:styled-content style="fixed-case">RCT</jats:styled-content>s is required. The <jats:styled-content style="fixed-case">EAACI TF</jats:styled-content> highlights the <jats:styled-content style="fixed-case">CSMS</jats:styled-content> as the primary endpoint for future <jats:styled-content style="fixed-case">RCT</jats:styled-content>s in <jats:styled-content style="fixed-case">AIT</jats:styled-content> for allergic rhinoconjunctivitis.</jats:p></jats:sec>