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Original Investigation
February 14, 2017

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 RhinitisThe GRASS Randomized Clinical Trial

Author Affiliations
  • 1Imperial College, London, and Royal Brompton and Harefield Hospitals NHS Foundation Trust, London, United Kingdom
  • 2Rho Federal Systems Division, Chapel Hill, North Carolina
  • 3currently with the Immune Tolerance Network, Benaroya Research Institute, Seattle, Washington
  • 4Immune Tolerance Network, Bethesda, Maryland
  • 5Immune Tolerance Network, San Francisco, California
  • 6National Institute of Allergy and Infectious Diseases, Rockville, Maryland
  • 7currently with the Department of Early Development Hematology/Oncology, Amgen, San Francisco, California
JAMA. 2017;317(6):615-625. doi:10.1001/jama.2016.21040
Key Points

Question  Does 2 years of grass pollen sublingual immunotherapy reduce symptoms after nasal allergen challenge at 3-year follow-up (1 year after discontinuation of treatment)?

Findings  In this randomized clinical trial of 106 adults, 2 years of treatment with sublingual immunotherapy, compared with placebo, did not significantly reduce total nasal symptom scores after challenge at 3 years.

Meaning  Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different than placebo in improving the nasal response to allergen challenge at 3-year follow-up.

Abstract

Importance  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.

Objective  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.

Design, Setting, and Participants  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.

Interventions  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).

Main Outcomes and Measures  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.

Results  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]).

Conclusions and Relevance  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.

Trial Registration  clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16

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