title: Prolonged efficacy of the 300IR 5-grass pollen tablet up to 2 years after treatment cessation, as measured by a recommended daily combined score.
abstract: BACKGROUND
  The 300IR (index of reactivity) 5-grass pollen tablet has favorable short-term and sustained clinical efficacy in patients with grass pollen-induced allergic rhinoconjunctivitis (ARC). Here, we report maintenance of efficacy and safety over 2 years following treatment discontinuation.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 3 trial in patients aged 18-50 years with ARC. During study years 1-3, patients received a daily sublingual tablet containing either 300IR 5-grass pollen extract or placebo, according to a discontinuous pre- and coseasonal protocol. Study years 4 and 5 were treatment-free. In response to health authorities' recommendations, the daily combined score (DCS) was assessed in a post-hoc analysis as the efficacy endpoint. Components of the DCS were daily rhinoconjunctivitis total symptom score (DRTSS) and daily rescue medication score (DRMS).
  
  
  RESULTS
  633 patients with ARC were randomized to placebo (n = 219) or 300IR 5-grass pollen tablet, beginning 4 months (4 M, n = 207) or 2 months (2 M, n = 207) prior to the estimated start of the grass pollen season and continuing until season's end. During the first post-treatment year, a statistically significant difference versus placebo in least squares (LS) mean DCS was noted in patients previously receiving active treatment (300IR (2 M) point estimate: -0.16, 95% confidence interval (CI95%): [-0.26, -0.06], p = 0.0019; -31.1%; 300IR (4 M) point estimate: -0.13, CI95%: [-0.23, -0.03], p = 0.0103, -25.3%). During the second post-treatment year, patients in the 300IR (4 M) group, but not the 300IR (2 M) group, showed a statistically significant difference in LS mean DCS versus placebo (point estimate: -0.11, CI95%: [-0.21; 0.00], p = 0.0478, -28.1%). This significant efficacy seen during the post-treatment years in patients previously treated with 5-grass pollen tablet compared favorably with that during the 3 prior years of active treatment. A statistically significant difference versus placebo was also noted in secondary efficacy measures in both post-treatment years (except for DRTSS in year 5). In the absence of any active treatment, the safety profile was similar in the active groups versus placebo group during either post-treatment year.
  
  
  CONCLUSIONS
  In adults with grass pollen-associated ARC, 5-grass pollen tablet therapy beginning 4 months before the pollen season and continuing to season's end demonstrated efficacy across all variables during active treatment, and this effect was prolonged for up to 2 years post-treatment.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00418379.
authors.affiliation: Rangueil-Larrey Hospital, Department of Respiratory Diseases, 24 Chemin de Pouvourville, TSA 30030 31059 Toulouse, Cedex 9 France.
authors.forename: Alain
authors.initials: A
authors.lastname: Didier
authors.affiliation: Allergy Clinic, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Hans-Jørgen
authors.initials: HJ
authors.lastname: Malling
authors.affiliation: Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
authors.affiliation: Vienna Challenge Chamber, Institute for Allergy Research, Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Horak
authors.affiliation: Division of Allergy and Clinical Immunology, University of Toronto, Toronto, ON Canada.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Sussman
keywords: 5-grass pollen tablet; Allergen-specific immunotherapy; Allergic rhinitis; Allergic rhinoconjunctivitis; Long-term efficacy Sublingual immunotherapy