Immunological effects and tolerability of a new fast updosed immunologically enhanced subcutaneous immunotherapy formulation with optimized allergen/adjuvant ratio

Authors


  • Edited by: Thomas Bieber

Correspondence

PD Dr. Med. Eike Wüstenberg, Medical and Regulatory Affairs, ALK, Feldstraße 170, D-22880 Wedel, Germany.

Tel.: +49-4103-7017312

Fax: +49-4103-7017730

E-mail: eike.wuestenberg@alk-abello.com

Abstract

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, IgG4 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.

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