title: A phase 3 trial assessing the efficacy and safety of grass allergy immunotherapy tablet in subjects with grass pollen-induced allergic rhinitis with or without conjunctivitis, with or without asthma.
abstract: BACKGROUND
  Design and execution of immunotherapy trials for seasonal allergies may be complicated by numerous factors including variable allergy testing methods, pollen levels, and timing and intensity of other seasonal allergens. We evaluated grass allergy immunotherapy tablet (AIT) treatment in North American adults with grass pollen-induced allergic rhinitis with or without conjunctivitis (AR/C), with/without asthma.
  
  
  METHODS
  Subjects age 18-65 with clinical history of grass pollen-induced AR/C, with/without asthma were randomized 1:1 to once-daily 2800 BAU Timothy grass AIT (oral lyophilisate, Phleum pratense, 75,000 SQ-T, containing approximately 15 μg of Phl p 5) or placebo. The AR/C symptom and medication scores were recorded daily. The primary end point was the average AR/C daily symptom score (DSS) during the entire grass pollen season (GPS). Ranked key secondary end points were Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, daily medication score (DMS), and percentage of well days, all over entire GPS. Safety was monitored through adverse event reporting.
  
  
  RESULTS
  Efficacy analysis included 289 subjects. Over the entire GPS, mean DSS was 6% lower with AIT versus placebo (5.69 vs. 6.06), but this difference was not statistically significant (p = 0.3475) despite significantly higher immunological response in the grass AIT group. No significant between-group differences were seen for key secondary end points. In general, DSS was high before GPS began and no clear relationship between DSS and grass pollen counts was seen during GPS. In post hoc analysis of subjects with pre-seasonal DSS ≤3, mean DSS and DMS were both significantly lower with grass AIT versus placebo (27%; p = 0.0327 and 68%; p = 0.0060, respectively). In this subgroup a relationship between DSS and grass pollen counts was observed. Grass AIT was generally well tolerated, with no events of anaphylactic shock or respiratory compromise.
  
  
  CONCLUSIONS
  In this trial, 2800 BAU grass AIT did not demonstrate significant symptom improvement versus placebo. Lack of relationship between pollen count and symptom score in the study population, and post hoc findings among subjects with low pre-seasonal symptoms, suggest that the symptoms reported in this study were not primarily reflective of the effects of grass pollen exposure.
  
  
  BACKGROUND
  NCT00421655.
authors.forename: Kevin
authors.initials: K
authors.lastname: Murphy
authors.forename: Sandra
authors.initials: S
authors.lastname: Gawchik
authors.forename: David
authors.initials: D
authors.lastname: Bernstein
authors.forename: Jens
authors.initials: J
authors.lastname: Andersen
authors.forename: Martin Rud
authors.initials: MR
authors.lastname: Pedersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000139:chemically induced / Q000175:diagnosis; D052179:Antigens, Plant / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D013607:Tablets; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D052179:Antigens, Plant; D010936:Plant Extracts; D013607:Tablets; C451253:grass pollen extract, alum-adsorbed