Dosing and efficacy in specific immunotherapy

P>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 mu g of allergen Phl p 5 per day) are ineffective. Daily doses of 15-25 mu g of the major allergen protein are required for significant clinical improvement measured by symptom scores. A higher dose (33-40 mu g of Phl p 5 per day) was not more effective than 15-25 mu g. 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.