Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti–IL-4: A randomized controlled trial - 05/02/16
Abstract |
Background |
Allergen immunotherapy is currently the only disease-modifying treatment available for allergic rhinitis and allergic asthma.
Objectives |
We sought to evaluate the induction of sustained tolerance to allergen when anti–IL-4 was combined with a suboptimal course of grass pollen subcutaneous immunotherapy (SCIT) using the allergen-induced skin late-phase response (LPR) and exploratory immune monitoring as surrogate markers of therapeutic response.
Methods |
In this randomized, double-blind, 3-group parallel design trial, 37 participants with seasonal allergic rhinitis received suboptimal SCIT (30,000 standardized quality units) in combination with anti–IL-4 (VAK694) and suboptimal SCIT (30,000 standardized quality units) plus placebo antibody or double placebo (placebo SCIT and placebo antibody) restricted to 13 weeks before the grass pollen season. The primary end point was the size of the LPR at 12 months. Exploratory end points included measures of the immunomodulatory activity of treatment by using IL-4 and IL-10 FluoroSpot assays, flow cytometry of T cells, and measurement of IgE, IgG4, and facilitated antigen binding.
Results |
Both active treatment arms led to a substantial and sustained reduction of the LPR with no additional suppression with addition of anti–IL-4. Treatment with anti–IL-4 and SCIT compared with SCIT alone led to a sustained reduction in allergen-specific IL-4–producing cell counts (P < .01). Both active treatment arms led to induction of dual IL-4/IL-10–producing cells during the pollen season.
Conclusion |
The combination of anti–IL-4 with SCIT provided no additional benefit over SCIT alone in suppressing the allergen-induced skin LPR. A larger trial is needed to assess whether the observed ex vivo downregulation of TH2 responses might translate into clinical benefit.
Le texte complet de cet article est disponible en PDF.Key words : Allergic rhinitis, subcutaneous allergen immunotherapy, anti–IL-4, FluoroSpot, intradermal late-phase response
Abbreviations used : AE, AIT, Cmax, CRTH2, FAB, FOXP3, FSC, LPR, mRQLQ, PVDF, SCIT, SQ, SSC, Treg, VAS
Plan
Supported by Novartis (CVAK694 A2205). |
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Disclosure of potential conflict of interest: A. M. Chaker has received a grant and travel support from Novartis; has consultant arrangements with Allergopharma, ALK-Abelló, HAL Allergy, Mundipharma, and Lofarma; has received grants from Allergopharma, the German Federal Environmental Agency, and Zeller AG; has received payment for lectures from Allergopharma, ALK-Abelló, and GlaxoSmithKline; has received payment for manuscript preparation from Bayerisches Ärzteblatt; and has received travel support from the European Academy of Allergy and Clinical Immunology, DGAKI, and SMI. F. A. Dumitru has received grants from Novartis and travel support from Zeller AG. M. A. Calderon has consultant arrangements with ALK-Abelló, Stallergenes, and HAL Allergy and has received payment for lectures from ALK-Abelló, Stallergenes, HAL Allergy, Allergopharma. Q. A. He is employed by Novartis Institutes for Biomedical Research. K. K. Subramanian is employed by Novartis. J. P. Arm is employed by Novartis and holds stock in Novartis. S. R. Durham has received grants from Novartis, Biotech Tools, and Regeneron USA; has consultant arrangements with Circassia and Biomay; has provided expert testimony for Merck; has received payment for lectures from Pneumo Update GMBH; and has received travel support from Boehringer Ingelheim. C. B. Schmidt-Weber has received grants from Novartis, DZL, and DFG; is chair of the immunology section for the European Academy of Allergy and Clinical Immunology; has consultant arrangements with Allergopharma, Leti Pharma, and PLS Design; has provided expert testimony for Research Council Norway; and has received payment for lectures from Allergopharma and Leo Pharma. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 2
P. 452 - février 2016 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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