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Randomised Placebo-Controlled Trial of Grass Pollen Allergen Tablet Immunotherapy for Seasonal Rhinitis: Clinical and Surrogate Outcomes and Early Time Course of Immunologic Changes
Sunday, March 6, 2016: 4:45 PM
Concourse Foyer (Convention Center)
Esther H Steveling, MD, Mongkol Lao-Araya, MD, Christopher Koulias, MD, Merajur Chowdhury, Guy Scadding, MRCP, Aarif Eifan, MD, Alina Dumitru, MD PhD, Martin J. Penagos Paniagua, MD, Mohamed H. Shamji, BSc MSc PhD FAAAAI, Stephen R. Durham, MA MD FRCP
Rationale: Sublingual grass pollen tablet immunotherapy (AIT) is effective and results in longterm clinical benefits. The early time course of systemic B and T cell responses has not been studied. 

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.