title: 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.
authors.affiliation: Allergy and Clinical Immunology, Imperial College London, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: H S
authors.initials: HS
authors.lastname: Nelson
authors.forename: H
authors.initials: H
authors.lastname: Nolte
authors.forename: D I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: P S
authors.initials: PS
authors.lastname: Creticos
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: J S
authors.initials: JS
authors.lastname: Andersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006109:Poaceae / Q000009:adverse effects*; D011058:Pollen / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000628:therapy*; D012621:Seasons; D063729:Sublingual Immunotherapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens
keywords: allergen-specific immunotherapy; grass pollen counts; grass sublingual immunotherapy tablet