BACKGROUND: Placebo control in allergen immunotherapy (AIT) trials presents ethical and blinding concerns. We tested a trial design with an "active allergen placebo," as proposed by ARIA-GA(2) LEN, to investigate in a double-blind trial the efficacy and safety of AIT in dual-allergic patients (grass and birch pollen) using active untargeted treatments as controls. METHODS: We randomized 95 patients to receive either grass (N = 47) or birch AIT (N = 48). Patients were exposed to both allergens in an allergen challenge chamber (ACC) before and after 9 months of AIT. Targeted (ACC-allergen = AIT-allergen) and untargeted (ACC-allergen not equal AIT-allergen) treatment effects were assessed. RESULTS: Immunotherapy reduced significantly the mean (95% confidence interval) area under the curve of total nasal symptom score (targeted effects) by -13.55 (-17.56, -9.54; P < 0.001) after grass and -9.81 (-14.13, -5.50; P < 0.001) after birch AIT. Differences in targeted vs untargeted effects between AIT groups (utility of control group) were statistically significant for both grass (P = 0.02) and birch (P = 0.02) allergens. Targeted vs untargeted differences within-treatment groups (specificity of ACC measurement) were significant for grass AIT (P < 0.001) but not significant for birch AIT group (P = 0.24). Specific immunoglobulin G4 to both allergens increased significantly (P < 0.001) after targeted treatment, while remained unchanged for untargeted treatments. Both treatments were well tolerated. CONCLUSIONS: Immunotherapies for both grass and birch allergens were efficacious and safe. The study confirms the specificity of AIT. Untargeted treatment groups could serve as controls in future AIT trials.
- Wagenmann, M.
- Worm, M.
- Akboga, Y.
- Karjalainen, M.
- Hohlfeld, J. M.
Keywords
- *active allergen placebo
- *active control group
- *allergen challenge chamber
- *allergen immunotherapy
- *dual allergy
