Methods: 301 (PP) patients with confirmed rhinitis and/or rhinoconjunctivitis were treated in a double-blind study with 4 doses of 100 DPP/ml, 1000 DPP/ml, 5000 DPP/ml and 10.000 DPP/ml allergen extract over 22 weeks in Germany, Poland, and Lithuania. A 1-day build-up phase applying 0.1 ml and 2 times 0.2 ml allergen extract was followed by a maintenance period applying 0.5 ml in 3-4 weeks intervals. Before treatment a CPT was performed with semi-logarithmically increasing doses up to 10.000 SQ-U/ml of native birch extract, after treatment the CPT was repeated with doses up to 100.000 SQ-U/ml. The main parameter was the percentage of patients with an increase of allergen extract to provoke a positive CPT after SIT. Secondary parameters were specific IgE, IgG1 and IgG4 as well as safety.The main parameter was investigated using a hierarchic test procedure comparing the highest dose against the lowest, if statistically significant testing the next lower dose against the lowest until the difference was no longer significant.
Results: An increase in allergen amount to provoke a positive CPT after SIT was reached in 37.5% of the 100 DPP/ml, 50.7% of the 1000 DPP/ml , 54.9% of the 5000 DPP/ml and 55.8% of the 10.000 DPP/ml group. Results compared to the lowest dose were statistically significant for the 5000 DPP/ml (p=0.0236) and 10.000 DPP/ml group (p=0.0159). Specific IgEs remained stable in all groups whereas specific IgG1 and IgG4 showed dose-dependent increases. Grade 1 systemic reactions occurred in 18% (100 DPP/ml), 14.8% (1000 DPP/ml), 17.4% (5000 DPP/ml) and 25.3% (10.000 DPP/ml) of patients.
Conclusions: We determined increased allergen amounts to obtain a positive CPT after SIT from 1000 -10.000 DPP/ml depigmented polymerized birch pollen extract. The 5000 DPP/ml dose extract suggest a good benefit/risk ratio with the potential for further development.