A Randomized Placebo-Controlled Trial of Intradermal Grass Pollen Immunotherapy for Seasonal Allergic Rhinitis

Abstract

Rationale: We previously reported that repeated intradermal injection of grass pollen (nanograms of allergen) almost completely suppresses allergen-induced cutaneous late phase responses (JACI 2012 130(4):918-24). Similar suppression of late responses is seen after high dose subcutaneous and sublingual immunotherapy. We therefore evaluated the efficacy of grass pollen intradermal immunotherapy (IDIT) for treatment of allergic rhinitis. Methods: 93 adults with grass pollen allergic rhinitis were randomized to receive 7 pre-seasonal IDIT injections (7 ng of Phl p 5 major allergen) or histamine control at 2-weekly intervals. The primary end point was combined daily symptom/medication scores (CSMS) during 2013 pollen season. Skin biopsies were taken after the pollen season following intradermal allergen challenges. Cutaneous late responses were measured 4 and either 7, 10 or 13 months post-treatment. Results: No difference in CSMS was observed between treatment arms. Paradoxically, amongst secondary endpoints, nasal symptoms measured with daily scores (P=0.03) and visual analog scales (P=0.05) were higher in the IDIT group. IDIT also increased serum Phl p-specific IgE (P=0.001) compared to the control arm. T cells cultured from skin biopsies of IDIT subjects showed higher and lower expression of surface markers for Th2 (P=0.04) and Th1 (P=0.01) cells, respectively, together with higher expression of IL-5 mRNA measured by microarray. Late responses to grass pollen were still inhibited 7 months after IDIT (P=0.03). Conclusions: Although grass pollen IDIT suppressed skin late responses, it was not clinically effective but resulted in immunological priming and worsening of allergic rhinitis symptoms.