title: Efficacy and safety of ragweed sublingual immunotherapy in Canadian patients with allergic rhinoconjunctivitis.
abstract: BACKGROUND
  Currently accepted therapies for ragweed allergy in North America consist of pharmacotherapy and subcutaneous allergen immunotherapy injections to treat symptoms. Allergen immunotherapy not only reduces symptoms and the need for pharmacotherapy but has also been shown to have disease-modifying potential. Recently, ragweed immunotherapy administered via sublingual allergen tablet has been approved in North America for treatment of allergic rhinitis with and without conjunctivitis.
  
  
  METHODS
  This was an analysis of pooled data for a prespecified subgroup of Canadian subjects from two multicentre, randomized, double-blind placebo-controlled trials of ragweed sublingual tablet (SLIT-T; 6 and 12 Amb a 1-U of Ambrosia artemisiifolia) in patients aged ≥18y, with ragweed-induced allergic rhinoconjunctivitis (AR/C) with or without asthma. Randomized subjects used once-daily ragweed SLIT-T or placebo for at least 12 weeks before the ragweed season and for up to 52 weeks post-randomization. The primary efficacy endpoint was the total combined score (TCS) based on the sum of AR/C daily symptom score (DSS) and daily medication score (DMS) averaged over the peak season. Treatment effects on TCS, DSS, and DMS in the entire season were also assessed. Adverse events (AEs) were monitored to assess safety.
  
  
  RESULTS
  337 Canadian subjects were randomized in the two trials. During the peak season, ragweed SLIT-T 6 and 12 Amb a 1-U significantly reduced TCS by 26% (difference, -2.46 score point; p = .0009) and 40% (difference, -3.75 score point; p < .0001), respectively. In the overall population (N = 961), TCS reductions with 6 and 12 Amb a 1-U were 20% and 23%, respectively (both p < .001). Clinically meaningful reductions in entire-season TCS in Canadians were similar to those during peak ragweed season. Dose-dependent reduction of DSS and DMS was also observed for ragweed SLIT-T 6 and 12 Amb a 1-U during the peak season and the entire season. Ragweed SLIT-T was well tolerated in Canadian subjects and the overall population. Adverse events were generally mild to moderate and transient, occurring early in treatment; no systemic allergic reaction/anaphylaxis was noted.
  
  
  CONCLUSIONS
  Ragweed SLIT-T is an effective form of immunotherapy that provides symptomatic efficacy of AR/C with a favorable risk profile in Canadian and overall populations.
  
  
  BACKGROUND
  Clinicaltrials.gov identifiers NCT00783198 and NCT00770315.
authors: McMaster University, Hamilton, ON Canada ; Western University, London, ON Canada ; 525 Belmont Ave West, Suite 205, Kitchener, ON N2M 5E2 Canada.
authors: Harold
authors: H
authors: Kim
authors: McMaster University, Hamilton, ON Canada.
authors: Susan
authors: S
authors: Waserman
authors: Centre de Recherche Appliquée en Allergie de Québec, Québec, QC Canada.
authors: Jacques
authors: J
authors: Hébert
authors: University of Tennessee Health Science Center, Memphis, TN USA.
authors: Michael
authors: M
authors: Blaiss
authors: National Jewish Health, Denver, CO USA.
authors: Harold
authors: H
authors: Nelson
authors: Johns Hopkins University School of Medicine, Baltimore, MD USA ; Creticos Research Group, Crownsville, MD USA.
authors: Peter
authors: P
authors: Creticos
authors: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors: Amarjot
authors: A
authors: Kaur
authors: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors: Jennifer
authors: J
authors: Maloney
authors: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors: Ziliang
authors: Z
authors: Li
authors: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors: Hendrik
authors: H
authors: Nolte
keywords: Allergen immunotherapy; Allergic rhinitis; Conjunctivitis; Ragweed pollen; SLIT; Sublingual immunotherapy Tablet