Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients
(2013) In Clinical and Translational Allergy 3(16).- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4058038
- author
- Rieker-Schwienbacher, Juliane ; Nell, Marja J ; Diamant, Zuzana LU ; van Ree, Ronald ; Distler, Andreas ; Boot, Johan D and Kleine-Tebbe, Jörg
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Allergic rhinitis, Allergic rhinoconjunctivitis, Conjunctival provocation test, House dust mites, Subcutaneous allergoid immunotherapy, Tolerability, Safety, Short-term effects
- in
- Clinical and Translational Allergy
- volume
- 3
- issue
- 16
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:23657148
- scopus:85006086285
- ISSN
- 2045-7022
- DOI
- 10.1186/2045-7022-3-16
- language
- English
- LU publication?
- yes
- id
- 28c6751e-70f8-4105-821c-7bd423486cbf (old id 4058038)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/?term=23657148
- date added to LUP
- 2016-04-01 13:44:37
- date last changed
- 2022-04-06 06:49:54
@article{28c6751e-70f8-4105-821c-7bd423486cbf,
abstract = {{Background<br/><br>
<br/><br>
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.<br/><br>
Methods<br/><br>
<br/><br>
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.<br/><br>
Results<br/><br>
<br/><br>
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.<br/><br>
Conclusions<br/><br>
<br/><br>
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.}},
author = {{Rieker-Schwienbacher, Juliane and Nell, Marja J and Diamant, Zuzana and van Ree, Ronald and Distler, Andreas and Boot, Johan D and Kleine-Tebbe, Jörg}},
issn = {{2045-7022}},
keywords = {{Allergic rhinitis; Allergic rhinoconjunctivitis; Conjunctival provocation test; House dust mites; Subcutaneous allergoid immunotherapy; Tolerability; Safety; Short-term effects}},
language = {{eng}},
number = {{16}},
publisher = {{BioMed Central (BMC)}},
series = {{Clinical and Translational Allergy}},
title = {{Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients}},
url = {{https://lup.lub.lu.se/search/files/3565443/4058050.pdf}},
doi = {{10.1186/2045-7022-3-16}},
volume = {{3}},
year = {{2013}},
}