title: Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients.
abstract: BACKGROUND
  The current maintenance dose (10,000 AUeq/monthly) of a subcutaneous allergoid for house dust mite (HDM) immunotherapy has previously shown significant clinical efficacy in patients with HDM induced allergic rhinitis or rhinoconjunctivitis. In order to comply with the 2009 EMA guidelines on immunotherapy products, a study was conducted to evaluate the safety, tolerability and short-term treatment effects of up-dosing regimens with high doses (up to 40,000 AUeq) of allergoid HDM immunotherapy.
  
  
  METHODS
  In total 48 patients with HDM-allergic rhinitis or rhinoconjunctivitis (29 M/19 F; 18-53 years) were included and enrolled into one of three up-dosing regimens (1:4:4): 1) a regular regimen with up-dosing to 40,000 AUeq followed by two maintenance doses (total duration 17 weeks), 2) an intermediate regimen (14 weeks) or 3) a fast regimen (11 weeks). Safety and tolerability were evaluated by monitoring of early and late local reactions and systemic reactions. In addition, short-term effects were assessed by conjunctival provocation test (CPT) and levels of serum allergen-specific IgE, IgG and IgG4.
  
  
  RESULTS
  Thirty-nine patients completed the study according to protocol. No early local reactions occurred. Late local reactions (LLR) were observed in 12% of the injections. In total, 31 systemic reactions, all grade 1, were reported of which two needed oral antihistamine treatment. No grade 2 or higher systemic reactions were observed. Six patients (15%) did not reach the highest dose due to LLR and/or systemic reactions needing antihistamines (20% in the regular regimen, 16% in the intermediate regimen and 13% in the fast regimen). At the end of the study, an improvement in the CPT was observed in 82.1% of patients, indirectly indicating an early treatment effect at the current dose and higher doses. In addition, IgG4 immunoglobulin levels were significantly increased in all groups following treatment.
  
  
  CONCLUSIONS
  In this open-label study, allergoid HDM immunotherapy in doses up to 40,000 AUeq was generally well tolerated and no clinically relevant safety issues were identified. In the safety aspects of the three up-dosing regimens no clinically relevant differences were encountered. Therefore, these dose ranges and up-dosing regimens can be safely included in future dose-finding efficacy studies.
authors: HAL Allergy BV, JH Oortweg 15, Leiden, The Netherlands. mnell@hal-allergy.com.
authors: Juliane
authors: J
authors: Rieker-Schwienbacher
authors: Marja J
authors: MJ
authors: Nell
authors: Zuzana
authors: Z
authors: Diamant
authors: Ronald
authors: R
authors: van Ree
authors: Andreas
authors: A
authors: Distler
authors: Johan D
authors: JD
authors: Boot
authors: Jörg
authors: J
authors: Kleine-Tebbe
references: Curr Allergy Asthma Rep. 2006 Sep;6(5):413-9
references: 16899204
references: Int Arch Allergy Immunol. 2009;148(3):251-60
references: 18849616
references: J Investig Allergol Clin Immunol. 2006;16(3):194-202
references: 16784014
references: N Engl J Med. 1999 Aug 12;341(7):468-75
references: 10441602
references: J Allergy Clin Immunol. 1997 Apr;99(4):450-3
references: 9111487
references: Allergy. 2004 Jun;59(6):589-95
references: 15147443
references: J Allergy Clin Immunol. 1985 Aug;76(2 Pt 2):397-401
references: 3926854
references: Am J Rhinol Allergy. 2010 Sep-Oct;24(5):e104-9
references: 21244725
references: J Allergy Clin Immunol. 1993 Mar;91(3):709-22
references: 8454793
references: Allergy. 1993;48(14 Suppl):9-35
references: 8342741
references: Allergol Immunopathol (Madr). 2001 Sep-Oct;29(5):191-6
references: 11720652
references: Drug Saf. 1994 Jan;10(1):5-17
references: 8136087
references: Allergy. 2000 Sep;55(9):842-9
references: 11003448
references: Clin Exp Allergy. 2009 Dec;39(12):1903-9
references: 20085600
references: Int Arch Allergy Immunol. 2003 Jan;130(1):51-9
references: 12576735
references: J Allergy Clin Immunol. 2010 Jan;125(1):131-8.e1-7
references: 20109743
references: J Allergy Clin Immunol. 2002 Feb;109(2):251-6
references: 11842293
references: Clin Exp Allergy. 2006 Mar;36(3):254-60
references: 16499635
references: Allergy. 1994 Feb;49(2):100-7
references: 8172356