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

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legal disclaimers that apply to the journal pertain.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.This project was awarded by the Efficacy and Mechanism Evaluation programme and is funded by the MRC and managed by NIHR on behalf of the MRC-NIHR partnership, and jointly sponsored by King’s College London and Guy’s & St Thomas’ NHS Foundation Trust. The funding source had no involvement in conduct of the research or preparation of the article. This work was also supported by the NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, and also the United Kingdom Clinical Research Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners, which is part funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Evaluation, Trials and Studies Coordinating Centre. Dr. Till was supported a HEFCE Clinical Senior Lectureship Award. Dr. Lam was funded by a MRC-Asthma UK funded PhD studentship. Dr. Slovick received funding from Athena SWAN and Royal College of Surgeons (England). Professor Cousins acknowledges support from NIHR Leicester Respiratory Biomedical Research UnitPeer-reviewedPost-prin