BACKGROUND: Sublingual immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose-finding study with a sublingual liquid birch pollen preparation (SB) was conducted. METHODS: Two hundred and sixty-nine adults with birch-pollen-induced AR were randomized to placebo, SB: 3333, 10,000, 20,000 or 40,000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch-pollen-specific immunoglobulin levels and peak nasal inspiratory flow (PNIF) were also measured (all measures determined outside the birch pollen season). RESULTS: In all treatment groups, an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high-dose groups (P = 0.008 and P < 0.001, respectively). For this primary endpoint, a significant linear dose-response curve was observed: the higher the dose, the better the improvement observed. Likewise, active treatment resulted in an increase in PNIF and serum IgG levels compared to placebo. The highest improvements were found in the 40,000 AUN/ml group. All active dosages resulted in more adverse reactions than placebo, which were mainly mild and well-controlled. CONCLUSIONS: A multicentre trial evaluated the dose-response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40,000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).

Center for Rhinology and Allergology Wiesbaden Germany

Department of Allergology and Immunology Medical Faculty in Plzen Charles University Prague Prague Czech Republic

Department of Otorhinolaryngology Head and Neck Surgery Medical Faculty Mannheim Universitätsmedizin Mannheim Heidelberg University Mannheim Germany

Department of Respiratory Medicine and Allergology Institute for Clinical Science Skane University Hospital Lund Sweden

Departments of Clinical Pharmacy and Pharmacology and General Practice University Medical Center Groningen University of Groningen Groningen The Netherlands

Departments of Experimental Immunology and of Otorhinolaryngology Academic Medical Center University of Amsterdam Amsterdam The Netherlands

Dept of Internal Medicine Asthma and Allergy Medical University of Lodz Lodz Poland

HAL Allergy BV Leiden The Netherlands

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ClinicalTrials.gov
NCT01639768