Magnitude of efficacy measurements in grass allergy immunotherapy trials is highly dependent on pollen exposure

Background The objective was to evaluate the association between grass pollen exposure, allergy symptoms and impact on measured treatment effect after grass sublingual immunotherapy (SLIT)-tablet treatment. Methods The association between grass pollen counts and total combined rhinoconjunctivitis symptom and medication score (TCS) was based on a post hoc analysis of data collected over six trials and seven grass pollen seasons across North America and Europe, including 2363 subjects treated with grass SLIT-tablet or placebo. Daily pollen counts were obtained from centralized pollen databases. The effect of treatment on the relationship between the TCS and pollen counts was investigated, and the relative difference between grass SLIT-tablet and placebo as a function of average grass pollen counts was modelled by linear regression. Results The magnitude of treatment effect based on TCS was greater with higher pollen exposure (P<0.001). The relative treatment effect in terms of TCS for each trial was correlated with the average grass pollen exposure during the first period of the season, with predicted reduction in TCS=12%+0.35%xpollen count (slope significantly different from 0, P=0.003; R-2=0.66). Corresponding correlations to the entire grass pollen season and to the peak season were equally good, whereas there was a poor correlation between difference in measured efficacy and pollen exposure during the last part of the season. Conclusions In seasonal allergy trials with grass SLIT-tablet, the observed treatment effect is highly dependent on pollen exposure with the magnitude being greater with higher pollen exposure. This is an important relationship to consider when interpreting individual clinical trial results.