title: Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: A randomized controlled trial.
abstract: BACKGROUND
  Allergen immunotherapy is currently the only disease-modifying treatment available for allergic rhinitis and allergic asthma.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom; Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Munich, Germany; Department of Otolaryngology, Allergy Section, Klinikum rechts der Isar, Technische Universität, Munich, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Chaker
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom; Immunomodulation and Tolerance group, Allergy and Clinical Immunology, Imperial College London, London, United Kingdom.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Shamji
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Florentina A
authors.initials: FA
authors.lastname: Dumitru
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Moises A
authors.initials: MA
authors.lastname: Calderon
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Guy W
authors.initials: GW
authors.lastname: Scadding
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Melina
authors.initials: M
authors.lastname: Makatsori
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, Mass, and Basel, Switzerland.
authors.forename: Ieuan
authors.initials: I
authors.lastname: Jones
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, Mass, and Basel, Switzerland.
authors.forename: Qiuling A
authors.initials: QA
authors.lastname: He
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, Mass, and Basel, Switzerland.
authors.forename: Kulandayan K
authors.initials: KK
authors.lastname: Subramanian
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, Mass, and Basel, Switzerland.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Arm
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom; Immunomodulation and Tolerance group, Allergy and Clinical Immunology, Imperial College London, London, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
authors.affiliation: Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom; Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Munich, Germany. Electronic address: csweber@tum.de.
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Schmidt-Weber
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D003131:Combined Modality Therapy; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D006109:Poaceae / Q000009:adverse effects*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D015415:Biomarkers; C508609:IL10 protein, human; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E
keywords: Allergic rhinitis; FluoroSpot; anti–IL-4; intradermal late-phase response; subcutaneous allergen immunotherapy