ENVIRONMENTAL FACTORS INFLUENCING SYMPTOMS AND USE OF RELIEF MEDICATIONS IN SUBJECTS WITH SEASONAL ALLERGIC RHINOCONJUNCTIVITIS

Abstract

<h3>Introduction</h3> In Phase III Allergen Immunotherapy (AIT) trials, the underlying assumption is that there is a causal relation between symptoms and allergen burden. However, there is a more complex interplay of allergen exposure and environmental variables. We report on a study where the impact of environmental factors has prospectively been taken into account to evaluate their impact on AIT treatment effects. <h3>Methods</h3> An exploratory field study comparing the efficacy of a modified grass subcutaneous immunotherapy product using MCT and MPL as adjuvant system (PQ Grass) versus placebo in subjects with allergic rhinitis/rhinoconjunctivitis was performed. The combined symptom and medication score (CSMS) during the peak grass pollen season was the primary endpoint. The daily pollen exposure as well as daily ozone and humidity levels were also collected. An exploratory analysis was defined using a hierarchical linear mixed model to evaluate the influence of these environmental variables on the primary endpoint results using observed cases. <h3>Results</h3> A statistically significant influence of daily humidity (p<0.001) in addition to the daily pollen burden on CSMS was demonstrated. When correcting the primary endpoint for these environmental factors the average CSMS improvement after PQ grass compared to placebo improved from 39.5% (based on the primary analysis model) without adjustment for environmental factors to 55.6% with adjustment (p<0.001) (observed cases). <h3>Conclusion</h3> Environmental conditions have an influence on the severity of the CSMS and correcting for these influences by introducing these as covariates may improve the primary outcome of Phase III AIT field studies.