Task Force on “Dose-Effect of SIT” (already completed)
Coordinator: MA Calderon
Start date: 2009; Finish date: 2011
Rationale: Clinical and immunological efficacy of SIT have been documented in many double-blind, placebo-controlled clinical trials. However, no consensus indication about dose-effect has been established. Different pre-seasonal or perennial schedules of treatment have been proposed and evaluated, all of them using different concentrations of single or multiples allergens. As a consequence, direct comparison of different preparations as reported in clinical trials is not feasible.
Main objectives of the project were:
To collect and compare clinical and immunological data on dose-efficacy of SIT for allergic rhinoconjunctivitis and asthma
To analyse dose-efficacy and dose-safety of venom SCITTo define optimal doses regarding systemic adverse reactions
The results of this TF have already been published in a TF-report in Allergy:
European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.
Allergy. 2011 Oct;66(10):1345-59.
For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects.
This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies.
Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made.
Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.
Dosing and efficacy in specific immunotherapy
Allergy. 2011 Jul;66 Suppl 95:38-40.
Allergen-specific immunotherapy is used to treat allergic rhinoconjuctivitis and asthma worldwide. The clinical efficacy of the most common routes, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, is documented for respiratory allergy by double-blind, placebo-controlled, randomised clinical trials (DB PC RCT). However, dose-effect relationships are not available for all extracts. The 1998 WHO Consensus Report on Allergen Immunotherapy found SCIT ineffective at low doses, with high doses more likely to result in an unacceptably high level of systemic reactions. Recent large well-designed DB PC RCTs using SLIT grass pollen tablets have undergone phase II-III studies in adults with allergic rhinitis, yielding proper dose-response studies. These were analysed by the European Academy of Allergy and Clinical Immunology Immunotherapy Interest Group task force on dose effect. In general, low doses (5-7 μg of allergen Phl p 5 per day) are ineffective. Daily doses of 15-25 μg of the major allergen protein are required for significant clinical improvement measured by symptom scores. A higher dose (33-40 μg of Phl p 5 per day) was not more effective than 15-25 μg. Optimization of the allergen/adjuvant ratio may allow for lower allergen doses, increase the safety/efficacy profile and allow for shorter updosing. However, our analysis of the available studies concluded that every product requires its own dose-response relationship study.