title: SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial.
abstract: BACKGROUND
  The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials.
  
  
  OBJECTIVE
  To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU,(∗) ALK, Denmark) or placebo.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters.
  
  
  RESULTS
  The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P ≤ .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by 20% to 45% (P ≤ .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P ≤ .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P ≤ .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified.
  
  
  CONCLUSIONS
  The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis.
authors.affiliation: Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College and Royal Brompton Hospital, London, United Kingdom. s.durham@imperial.ac.uk
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
authors.forename: Waltraud
authors.initials: W
authors.lastname: Emminger
authors.forename: Alexander
authors.initials: A
authors.lastname: Kapp
authors.forename: Jan G R
authors.initials: JG
authors.lastname: de Monchy
authors.forename: Sabina
authors.initials: S
authors.lastname: Rak
authors.forename: Glenis K
authors.initials: GK
authors.lastname: Scadding
authors.forename: Peter A
authors.initials: PA
authors.lastname: Wurtzen
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.forename: Bente
authors.initials: B
authors.lastname: Tholstrup
authors.forename: Bente
authors.initials: B
authors.lastname: Riis
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage* / Q000009:adverse effects; D006109:Poaceae; D011058:Pollen / Q000009:adverse effects; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D000485:Allergens; C551013:Grazax; D010936:Plant Extracts; D007073:Immunoglobulin E