Intradermal Grass Pollen Allergen Immunotherapy for Seasonal Allergy: A Randomized Controlled Trial.

BACKGROUND: Repeated low dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late phase responses, comparable with conventional subcutaneous and sublingual immunotherapy. OBJECTIVE: To evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. METHODS: We randomly assigned 93 adults with grass pollen allergic rhinitis to receive 7 pre-seasonal intradermal allergen injections (containing 7 nanograms of Phl p 5 major allergen) or histamine control. The primary endpoint was daily combined symptom-medication scores during the 2013 pollen season (area under curve). Analysis was by intention-to-treat. Skin biopsies were collected following intradermal allergen challenges and late phase responses measured four and seven, ten or thirteen months post-treatment. RESULTS: There was no significant difference in primary endpoint between treatment arms (active n=46, control n=47, median difference, 14; 95% CI -172.5-215.1; P=.80). Among secondary endpoints, nasal symptoms were worse in the intradermal treatment group, measured by daily scores (median difference, 35; 95% CI 4.0-67.5; P=.03) and visual-analog scales (median difference, 53; 95% CI -11.6-125·2; P=.05). In a per protocol analysis, intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom free days. Intradermal immunotherapy increased serum Phl p-specific IgE (P=.001) compared to the control arm. T cells cultured from biopsies of intradermal immunotherapy subjects showed higher expression of Th2 surface marker CRTH2 (P=.04) and lower Th1 marker CXCR (P=.01), respectively. Late phase responses remained inhibited seven months after treatment (P=.03). CONCLUSION: Intradermal allergen immunotherapy suppressed skin late responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.