Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti- XXXX : A  randomized controlled trial.

@entity1 @entity9285 @entity2023 @entity56 @entity3646 @entity688
BACKGROUND: Allergen immunotherapy is currently the only disease-modifying treatment available for @entity2023 and @entity56 . OBJECTIVES: We sought to evaluate the induction of sustained tolerance to allergen when anti- @entity3646 was combined with a suboptimal course of grass pollen @entity9285 ( @entity9285 ) 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 @entity1 with @entity2023 received suboptimal @entity9285 (30,000 standardized quality units) in combination with anti- @entity3646 (VAK694) and suboptimal @entity9285 (30,000 standardized quality units) plus placebo antibody or double placebo (placebo @entity9285 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 @entity3646 and @entity688 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- @entity3646 . Treatment with anti- @entity3646 and @entity9285 compared with @entity9285 alone led to a sustained reduction in allergen-specific @entity3646 -producing cell counts (P  <  .01). Both active treatment arms led to induction of dual @entity3646 / @entity688 -producing cells during the pollen season. CONCLUSION: The combination of anti- @entity3646 with @entity9285 provided no additional benefit over @entity9285 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.
