Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients

Clinical and Translational Allergy

Jörg Kleine-Tebbe⁵  Johan D Boot⁴  Andreas Distler³  Ronald van Ree¹  Zuzana Diamant²  Marja J Nell⁴  Juliane Rieker-Schwienbacher⁶ 

[1] Academic Medical Center (AMC), Department of Experimental Immunology and Department of Otorhinolaryngology, Meibergdreef 9, Amsterdam, The Netherlands;University Medical Centre Groningen, Dept. of General Practice, P.O. Box 196, Groningen, 9700 AD, The Netherlands;HAL Allergie GmbH, Poststrasse 5, Düsseldorf, Germany;HAL Allergy BV, JH Oortweg 15, Leiden, The Netherlands;Untersuchungszentrum Dermatologie, Allergologie und Asthma (UZDAA), Spandauer Damm 130 (Haus 9), Berlin, Germany;Klinikum Stuttgart, Klinik für Dermatologie und Allergologie, Priessnitzweg 24, Stuttgart, Germany

关键词: Short-term effects;    Safety;    Tolerability;    Subcutaneous allergoid immunotherapy;    House dust mites;    Conjunctival provocation test;    Allergic rhinoconjunctivitis;    Allergic rhinitis;   

Others  :  794337
DOI  :  10.1186/2045-7022-3-16

 received in 2012-12-18, accepted in 2013-04-28,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Rieker-Schwienbacher et al.; licensee BioMed Central Ltd.

【 图 表 】

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