title: Immunological effects and tolerability of a new fast updosed immunologically enhanced subcutaneous immunotherapy formulation with optimized allergen/adjuvant ratio.
abstract: BACKGROUND
  Subcutaneous immunotherapy (SCIT) traditionally includes an updosing phase injecting increasing doses of allergen over a period of several weeks, followed by a maintenance phase. To establish shorter and more convenient updosing schedules, a fast updosed immunologically enhanced SCIT formulation has been developed by optimizing the allergen/adjuvant (aluminium hydroxide) ratio.
  
  
  METHODS
  In a randomized, controlled, parallel-group trial, patients with grass pollen induced rhinoconjunctivitis with/without asthma were treated with an immunologically enhanced SCIT formulation (AVANZ, ALK, Denmark). The trial included updosing with five injections (300, 600, 3000, 6000 and 15,000 SQ+) injected either in weekly interval (Group 1) or in 3-4 days interval (Group 2) followed by two maintenance injections (15,000 SQ+), approximately 10 weeks treatment. The immunological effects (primary endpoint) and tolerability (secondary endpoint) of the updosing schedules were evaluated.
  
  
  RESULTS
  Four hundred patients were treated (Group 1: 201, Group 2: 199). In both groups, an immunological response with statistically significant increases in levels of IgE-blocking factor, IgG(4) and IgE (P < 0.001), was induced from baseline to end of trial. Most frequently reported adverse events were local injection site reactions such as injection site swellings (Group 1: 30% of patients, Group 2: 41% of patients). Other frequently reported adverse events included systemic reactions (Group 1: 21% of patients, Group 2: 33% of patients), primarily mild to moderate allergic rhinitis and urticaria.
  
  
  CONCLUSIONS
  Fast updosed immunologically enhanced SCIT with an optimized allergen/adjuvant ratio induced significant immunological effects and had an acceptable safety profile. Clinical efficacy will be investigated in future clinical trials.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Mannheim, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Pfaar
authors.forename: K
authors.initials: K
authors.lastname: Jung
authors.forename: H
authors.initials: H
authors.lastname: Wolf
authors.forename: E
authors.initials: E
authors.lastname: Decot
authors.forename: J
authors.initials: J
authors.lastname: Kleine-Tebbe
authors.forename: L
authors.initials: L
authors.lastname: Klimek
authors.forename: E
authors.initials: E
authors.lastname: Wüstenberg
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000009:adverse effects; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D006109:Poaceae / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000628:therapy*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E