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

Abstract

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% × pollen 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.

Keywords: allergen-specific immunotherapy; grass pollen counts; grass sublingual immunotherapy tablet.

Figure 1

Example of allergy immunotherapy trial course with a random pollen season.

Figure 2

Higher pollen counts increase magnitude of treatment effect based on total combined rhinoconjunctivitis score. The smoothing spline curves represent all available diary data from the included trials; that is, each point represents 1 day with diary data during the grass pollen season (left y-axis). The histogram shows the percentage of days with a given grass pollen count from 0 to 300 grains/m³ (right y-axis).

Figure 3

Correlation between relative difference in total combined rhinoconjunctivitis score (TCS) and the average grass pollen counts over the first 20 days of the grass pollen season for each of the included trials. The line is the fitted linear regression with 95% confidence intervals. −Y1−Y5 represent the five seasons included in the GT-08 trial.