title: The placebo effect in allergen-specific immunotherapy trials.
abstract: BACKGROUND
  Double-blind, placebo-controlled (DBPC) trials are the gold standard for demonstrating clinical efficacy and tolerability. The placebo effect, although an important feature in placebo-controlled studies, has never been systematically investigated in allergen-specific immunotherapy (SIT) studies. This study was performed to examine the placebo response in SIT trials that employed a baseline observational period and two treatment years using a symptom-medication-score (SMS) as the primary endpoint.
  
  
  METHODS
  The placebo effect was evaluated in six DBPC SIT studies (five studies using subcutaneous SIT (SCIT) and one sublingual (SLIT)), two grass, two birch and two house dust mite (HDM) SIT, including a total of 472 adult patients treated with a placebo. The results were reported as changes from baseline of the SMS area under the curve after two years of perennial placebo therapy during the respective evaluation periods. Pollen counts and IgG4 levels were additionally analysed.
  
  
  RESULTS
  Subcutaneously treated placebo patients displayed a marked decrease in the SMS. The mean placebo effect in the SCIT trials with comparable allergen exposure was up to 41% in the second treatment year and, in contrast, reached only 1% in the SLIT trial. Allergen exposure had an inverse influence on the placebo effect. No changes from baseline in allergen specific IgG4 antibodies were observed in the placebo-treated patients.
  
  
  CONCLUSIONS
  SIT studies display a significant placebo effect, mainly observed in subcutaneous immunotherapy, with high variability depending on the route of application and allergen exposure. Our findings indicate the differential role of the placebo effect in SIT efficacy depending on the route of administration and pollen exposure.
authors.affiliation: Medical Department, Allergopharma GmbH & Co KG, Reinbek, Germany. annemie.narkus@allergopharma.com.
authors.forename: Annemie
authors.initials: A
authors.lastname: Narkus
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lehnigk
authors.forename: Dietrich
authors.initials: D
authors.lastname: Haefner
authors.forename: Regine
authors.initials: R
authors.lastname: Klinger
authors.forename: Oliver
authors.initials: O
authors.lastname: Pfaar
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm