Methods: This single-centre, randomized, double-blind, placebo-controlled study (n=46) in moderate-severe hay fever compared daily AIT (Grazax ®, ALK-Abello Horsholm, Denmark) with placebo tablets. Primary outcome was total nasal symptom score [TNSS, 0-60 min] after nasal allergen challenge (NAC). Mechanistic outcomes were assessed before and at 1, 2, 3, 4 and 12 months. Statistical analysis was by linear mixed models applied to longitudinal data.
Results: At 12 months AIT resulted in lower TNSS (p<0.0001, mean difference (MD) -1.54, 95% confidence intervals [-2.03/-1.04]) paralleled by higher peak nasal inspiratory flows (p<0.001, MD 33.61 [13.57/53.65]) compared to placebo. Intradermal allergen resulted in decreased early (MD -4.92 [-8.14/-1.71], p<0.004) and late (MD -21.96 [-31.68/-12.24], p<0.0001) cutaneous responses. Global seasonal symptoms (visual analogue scale [0-100mm]) were 38.7% decreased, (MD -10.39 [-18.68/-2.10], p<0.015). At 4 weeks, peripheral blood mononuclear cell IL-10 (ELISA 6 day PBMC supernatants (MD 0.27 [0.05/0.48], p<0.015) and serum log sIgE kU/L (MD 0.45 [0.10/0.81], p<0.013) increased compared to placebo. There were delayed-in–time increases in log sIgG4(MD 0.23 [0.02/0.44], p<0.032) and decreases in plasma inhibitory activity for facilitated allergen binding (IgE-FAB) at 3 to 12 months (MD -61.36 [-76.94/-45.78], p<0.0001).
Conclusions: Sublingual AIT, compared to placebo, reduced allergen-induced nasal and cutaneous responses, improved seasonal symptoms and was accompanied by early increases in serum IgE, PBMC IL-10 and later progressive increases in ‘blocking’ IgG antibodies.