BACKGROUND:Subcutaneous immunotherapy (SCIT) traditionally includes an updosing phase injecting increasing doses of allergen over a period of several weeks, followed by a maintenance phase. To establish shorter and more convenient updosing schedules, a fast updosed immunologically enhanced SCIT formulation has been developed by optimizing the allergen/adjuvant (aluminium hydroxide) ratio. METHODS: In a randomized, controlled, parallel-group trial, patients with grass pollen induced rhinoconjunctivitis with/without asthma were treated with an immunologically enhanced SCIT formulation (AVANZ, ALK, Denmark). The trial included updosing with five injections (300, 600, 3000, 6000 and 15,000 SQ+) injected either in weekly interval (Group 1) or in 3-4 days interval (Group 2) followed by two maintenance injections (15,000 SQ+), approximately 10 weeks treatment. The immunological effects (primary endpoint) and tolerability (secondary endpoint) of the updosing schedules were evaluated. RESULTS:Four hundred patients were treated (Group 1: 201, Group 2: 199). In both groups, an immunological response with statistically significant increases in levels of IgE-blocking factor, IgG(4) and IgE (P < 0.001), was induced from baseline to end of trial. Most frequently reported adverse events were local injection site reactions such as injection site swellings (Group 1: 30% of patients, Group 2: 41% of patients). Other frequently reported adverse events included systemic reactions (Group 1: 21% of patients, Group 2: 33% of patients), primarily mild to moderate allergic rhinitis and urticaria. CONCLUSIONS: Fast updosed immunologically enhanced SCIT with an optimized allergen/adjuvant ratio induced significant immunological effects and had an acceptable safety profile. Clinical efficacy will be investigated in future clinical trials.
RCT Entities:
BACKGROUND: Subcutaneous immunotherapy (SCIT) traditionally includes an updosing phase injecting increasing doses of allergen over a period of several weeks, followed by a maintenance phase. To establish shorter and more convenient updosing schedules, a fast updosed immunologically enhanced SCIT formulation has been developed by optimizing the allergen/adjuvant (aluminium hydroxide) ratio. METHODS: In a randomized, controlled, parallel-group trial, patients with grass pollen induced rhinoconjunctivitis with/without asthma were treated with an immunologically enhanced SCIT formulation (AVANZ, ALK, Denmark). The trial included updosing with five injections (300, 600, 3000, 6000 and 15,000 SQ+) injected either in weekly interval (Group 1) or in 3-4 days interval (Group 2) followed by two maintenance injections (15,000 SQ+), approximately 10 weeks treatment. The immunological effects (primary endpoint) and tolerability (secondary endpoint) of the updosing schedules were evaluated. RESULTS: Four hundred patients were treated (Group 1: 201, Group 2: 199). In both groups, an immunological response with statistically significant increases in levels of IgE-blocking factor, IgG(4) and IgE (P < 0.001), was induced from baseline to end of trial. Most frequently reported adverse events were local injection site reactions such as injection site swellings (Group 1: 30% of patients, Group 2: 41% of patients). Other frequently reported adverse events included systemic reactions (Group 1: 21% of patients, Group 2: 33% of patients), primarily mild to moderate allergic rhinitis and urticaria. CONCLUSIONS: Fast updosed immunologically enhanced SCIT with an optimized allergen/adjuvant ratio induced significant immunological effects and had an acceptable safety profile. Clinical efficacy will be investigated in future clinical trials.
Authors: Jörg Kleine-Tebbe; Mikkel Walmar; Klaus Bitsch-Jensen; Elke Decot; Oliver Pfaar; Dolores Hernández Fernández de Rojas; Fernando Rodriguez Journal: Clin Drug Investig Date: 2014-08 Impact factor: 2.859