Chaker, A, Shamji, MH, Dumitru, A, Calderon, M, Scadding, G, Makatsori, M, Jones, Ieuan, He, Ally, Subramanian, Kulandayan, Arm, Jonathan, Durham, SR and Schmidt-Weber, CB (2016) Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: a randomised controlled trial. Journal of Allergy and Clinical Immunology.

Abstract

Background:
Allergen immunotherapy is highly effective in allergic rhinitis and allergic asthma and is currently the only disease-modifying treatment available. The aim of this study was to evaluate the induction of sustained tolerance to allergen when anti IL-4 (VAK694) was combined with a suboptimal course of grass pollen subcutaneous immunotherapy (SCIT) using the allergen-induced late phase skin response and exploratory immune monitoring as surrogate markers of therapeutic response.
Methods:
In this randomized, double-blind, three-group parallel design trial 37 participants with seasonal allergic rhinitis received grass pollen-specific immunotherapy (30.000 SQ) in combination with VAK694, grass-pollen SCIT (30.000 SQ) plus placebo-antibody or double placebo (placebo-SCIT & placebo-antibody) restricted to 13 weeks prior to the grass pollen season. The primary endpoint was the size of the skin late phase response (LPR) at 12 months later. Exploratory endpoints included measures of the immuno-modulatory activity of treatment by IL-4 and IL-10 Elispots, FACS, IgE, IgG4 and FAB.
Results:
Both active treatments arms led to a substantial and sustained reduction of the LPR with no additional suppression with the addition of VAK694. Treatment with VAK694 and suboptimal SCIT, compared to SCIT alone, led to a sustained reduction of allergen-specific IL-4 producing cells (p<0.01). Both active treatment arms led to the induction of IL-4/IL-10 producing cells.
Conclusion: Co-injection of allergen under the umbrella of anti-IL-4 in the up-dosing phase of allergen immunotherapy is effective in modulating Th2 responses in a long-lasting manner and may pave the way to rational vaccine design of allergen immunotherapy.

Item Type:	Article
Keywords:	Immunotherapy, IL-4, VAK694, allergy, grass pollen
Date Deposited:	17 Apr 2016 23:45
Last Modified:	17 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/24626