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

Peter Socrates Creticos, Robert E. Esch, Peter Couroux, Deborah Gentile, Pina D'Angelo, Brad Whitlow, Michael Alexander, Terrance C. Coyne

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)751-758
Number of pages8
JournalThe Journal of Allergy and Clinical Immunology
Volume133
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

Fingerprint

Sublingual Immunotherapy
Ambrosia
Immunologic Desensitization
Placebos
North America
Phase III Clinical Trials
Maximum Tolerated Dose
Anaphylaxis
Therapeutics
Erythema
Immunotherapy
Asthma
Randomized Controlled Trials
Safety
Skin

Keywords

  • Allergen-specific IgE
  • allergen-specific IgG
  • allergy immunotherapy
  • combined score
  • ragweed
  • specific immunotherapy
  • sublingual immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis. / Creticos, Peter Socrates; Esch, Robert E.; Couroux, Peter; Gentile, Deborah; D'Angelo, Pina; Whitlow, Brad; Alexander, Michael; Coyne, Terrance C.

In: The Journal of Allergy and Clinical Immunology, Vol. 133, No. 3, 03.2014, p. 751-758.

Research output: Contribution to journalArticle

Creticos, Peter Socrates ; Esch, Robert E. ; Couroux, Peter ; Gentile, Deborah ; D'Angelo, Pina ; Whitlow, Brad ; Alexander, Michael ; Coyne, Terrance C. / Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis. In: The Journal of Allergy and Clinical Immunology. 2014 ; Vol. 133, No. 3. pp. 751-758.
@article{ab00f7401e7840a4bd0dd22dbbbc06fa,
title = "Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis",
abstract = "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, allergy immunotherapy, combined score, ragweed, specific immunotherapy, sublingual immunotherapy",
author = "Creticos, {Peter Socrates} and Esch, {Robert E.} and Peter Couroux and Deborah Gentile and Pina D'Angelo and Brad Whitlow and Michael Alexander and Coyne, {Terrance C.}",
year = "2014",
month = "3",
doi = "10.1016/j.jaci.2013.10.041",
language = "English (US)",
volume = "133",
pages = "751--758",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis

AU - Creticos, Peter Socrates

AU - Esch, Robert E.

AU - Couroux, Peter

AU - Gentile, Deborah

AU - D'Angelo, Pina

AU - Whitlow, Brad

AU - Alexander, Michael

AU - Coyne, Terrance C.

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - Allergen-specific IgE

KW - allergen-specific IgG

KW - allergy immunotherapy

KW - combined score

KW - ragweed

KW - specific immunotherapy

KW - sublingual immunotherapy

UR - http://www.scopus.com/inward/record.url?scp=84896735209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896735209&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2013.10.041

DO - 10.1016/j.jaci.2013.10.041

M3 - Article

VL - 133

SP - 751

EP - 758

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -