title: Negative clinical results from a randomised, double-blind, placebo-controlled trial evaluating the efficacy of two doses of immunologically enhanced, grass subcutaneous immunotherapy despite dose-dependent immunological response.
abstract: OBJECTIVE
  Specific immunotherapy is the only treatment for the underlying allergic disease in patients with respiratory allergies. The primary objective of this trial was to evaluate the efficacy and safety of two maintenance doses of immunologically enhanced, standardised quality (SQ+) grass subcutaneous immunotherapy (SCIT) [4,000 SQ+ and 15,000 SQ+; AVANZ(®) Phleum pratense (ALK)] compared with placebo.
  
  
  METHODS
  This was a randomised, double-blind, placebo-controlled, phase II/III trial. The primary evaluation was based on the combined rhinoconjunctivitis score during the entire grass pollen season. Adult subjects with grass pollen-induced allergic rhinoconjunctivitis interfering with usual activities or sleep despite symptomatic medication use, were enrolled.
  
  
  RESULTS
  Four hundred and fifty subjects were randomised to receive either 4,000 SQ+ (n = 150), 15,000 SQ+ (n = 152) or placebo (n = 148). The average grass pollen exposure was 27 grains/m(3)/day. No statistically significant differences between the active groups and the placebo group were found for clinical endpoints (p > 0.05). Highly statistically significant (p < 0.001) increases in IgG4 and IgE-blocking factor were found for both active groups versus placebo. The most frequently reported adverse events were mild-to-moderate local injection-site reactions; events were generally more frequent with 15,000 SQ+ than with 4,000 SQ+ and placebo. The most common adverse events leading to premature discontinuation from the trial were anaphylactic reactions (one subject from the placebo group and five subjects from the 15,000 SQ+ group).
  
  
  CONCLUSIONS
  The inconclusive results were most probably influenced by a very low grass pollen season. Other factors such as the extent of the pre-seasonal treatment could potentially have contributed. The tolerability profile was acceptable for further development.
authors.affiliation: Allergy and Asthma Center Westend, Outpatient Clinic Hanf, Ackermann & Kleine-Tebbe, Spandauer Damm 130, Haus 9, 14050, Berlin, Germany, kleine-tebbe@allergie-experten.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleine-Tebbe
authors.forename: Mikkel
authors.initials: M
authors.lastname: Walmar
authors.forename: Klaus
authors.initials: K
authors.lastname: Bitsch-Jensen
authors.forename: Elke
authors.initials: E
authors.lastname: Decot
authors.forename: Oliver
authors.initials: O
authors.lastname: Pfaar
authors.forename: Dolores Hernández Fernández
authors.initials: DH
authors.lastname: de Rojas
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez
mesh_terms: D000293:Adolescent; D000328:Adult; D052179:Antigens, Plant / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D038622:Internationality; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D052179:Antigens, Plant; D010936:Plant Extracts; C451253:grass pollen extract, alum-adsorbed