title: Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial.
abstract: Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment.
  
  
  
  To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.
  
  
  
  A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.
  
  
  
  Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation).
  
  
  
  Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy.
  
  
  
  Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was -0.18 (95% CI, -1.25 to 0.90; [P = .75]).
  
  
  
  Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up.
  
  
  
  clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16.
authors.affiliation: Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Guy W
authors.initials: GW
authors.lastname: Scadding
authors.affiliation: Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Moises A
authors.initials: MA
authors.lastname: Calderon
authors.affiliation: Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Shamji
authors.affiliation: Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Aarif O
authors.initials: AO
authors.lastname: Eifan
authors.affiliation: Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Penagos
authors.affiliation: Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Florentina
authors.initials: F
authors.lastname: Dumitru
authors.affiliation: Rho Federal Systems Division, Chapel Hill, North Carolina.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Sever
authors.affiliation: Rho Federal Systems Division, Chapel Hill, North Carolina3currently with the Immune Tolerance Network, Benaroya Research Institute, Seattle, Washington.
authors.forename: Henry T
authors.initials: HT
authors.lastname: Bahnson
authors.affiliation: Rho Federal Systems Division, Chapel Hill, North Carolina.
authors.forename: Kaitie
authors.initials: K
authors.lastname: Lawson
authors.affiliation: Immune Tolerance Network, Bethesda, Maryland.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Harris
authors.affiliation: Immune Tolerance Network, San Francisco, California.
authors.forename: Audrey G
authors.initials: AG
authors.lastname: Plough
authors.affiliation: National Institute of Allergy and Infectious Diseases, Rockville, Maryland.
authors.forename: Joy Laurienzo
authors.initials: JL
authors.lastname: Panza
authors.affiliation: Immune Tolerance Network, Bethesda, Maryland.
authors.forename: Tielin
authors.initials: T
authors.lastname: Qin
authors.affiliation: Immune Tolerance Network, Bethesda, Maryland.
authors.forename: Noha
authors.initials: N
authors.lastname: Lim
authors.affiliation: Immune Tolerance Network, San Francisco, California7currently with the Department of Early Development Hematology/Oncology, Amgen, San Francisco, California.
authors.forename: Nadia K
authors.initials: NK
authors.lastname: Tchao
authors.affiliation: National Institute of Allergy and Infectious Diseases, Rockville, Maryland.
authors.forename: Alkis
authors.initials: A
authors.lastname: Togias
authors.affiliation: Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D000328:Adult; D000485:Allergens / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D031784:Phleum / Q000009:adverse effects / Q000276:immunology*; D011058:Pollen / Q000009:adverse effects / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000208:ethnology / Q000628:therapy*; D063729:Sublingual Immunotherapy / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000485:Allergens