Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms - 27/09/17
Abstract |
Background |
Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy.
Objective |
We sought 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–induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment.
Results |
There was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, −172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, −11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense–specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03).
Conclusion |
Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.
Le texte complet de cet article est disponible en PDF.Key words : Allergy immunotherapy, allergic rhinitis, grass pollen, Phleum pratense, immunotherapy, intradermal, low dose
Abbreviations used : APAAP, ARIA, AUC, BU, CRTH2, CXCR3, DC, IQR, Mini-RQLQ, PE, PollenLITE, VAS, WAO
Plan
| This project was awarded by the Efficacy and Mechanism Evaluation Programme and is funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (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 the United Kingdom Clinical Research Collaboration–registered King's Clinical Trials Unit at King's Health Partners, which is partially 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. S.J.T. was supported a HEFCE Clinical Senior Lectureship Award. E.P.S.L. was funded by a MRC-Asthma UK funded PhD studentship. A.S. received funding from Athena SWAN and Royal College of Surgeons (England). D.J.C. acknowledges support from NIHR Leicester Respiratory Biomedical Research Unit. |
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| Disclosure of potential conflict of interest: A. Slovick receives research support from the Royal College of Surgeons England and Rosetree Foundation and travel support from ALK-Abelló. A. Douiri receives research support from the National Institute for Health Research (NIHR)–Efficacy and Mechanism Evaluation Programme. J. L. Peacock receives grant support from the NIHR. D. J. Cousins receives grant support from the Medical Research Council (MRC), NIHR, and GlaxoSmithKline. S. R. Durham serves as a consultant for Circassia, Anergis, Biomay, Allergy Therapeutics, Boehringer Ingelheim, GlaxoSmithKline, and UCB; provided expert testimony for Merck; received grant support from ALK-Abelló, Merck, and Regeneron; and received payments for lectures from ALK-Abelló and Pneumo Update. S. J. Till receives grant support from the MRC, NIHR, and King's Health Partners; serves as a consultant for ALK-Abelló; and payment for lectures for Thermo Fisher. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 6
P. 1830 - juin 2017 Retour au numéro
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