Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis

J Allergy Clin Immunol. 2014 Mar;133(3):751-8. doi: 10.1016/j.jaci.2013.10.041. Epub 2013 Dec 12.


Background: Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis (ARC), but a lack of robust evidence has deterred its use in North America.

Objective: To determine the efficacy and tolerability of standardized glycerinated short ragweed sublingual allergen immunotherapy liquid (RW-SAIL) extract in subjects with ragweed-related ARC.

Methods: This phase 3, randomized, placebo-controlled trial was conducted in North America. Subjects (age range, 18-55 years) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed. Subjects self-administered the maximum tolerated dose of RW-SAIL (n = 218) or placebo (n = 211) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season. The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores (TCS).

Results: During the entire season, there was a 43% decrease in TCS in subjects treated with RW-SAIL compared with placebo. Similar decreases were observed in TCS between the 2 groups during peak season (42%) and in daily symptom scores during the entire (42%) and peak (41%) seasons. The occurrence of adverse events was similar between the treatment groups; most were mild in severity. Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited. No anaphylaxis occurred.

Conclusions: This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual standardized ragweed allergen immunotherapy liquid extract for the treatment of ARC.

Keywords: Allergen-specific IgE; allergen-specific IgG(4); allergy immunotherapy; combined score; ragweed; specific immunotherapy; sublingual immunotherapy.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Plant / immunology*
  • Conjunctivitis, Allergic / immunology
  • Conjunctivitis, Allergic / therapy*
  • Desensitization, Immunologic / adverse effects
  • Desensitization, Immunologic / methods*
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Plant Extracts / immunology*
  • Rhinitis, Allergic
  • Rhinitis, Allergic, Perennial / immunology
  • Rhinitis, Allergic, Perennial / therapy*


  • Antigens, Plant
  • Plant Extracts
  • ragweed pollen