title: A proof-of-concept, randomized, controlled trial of omalizumab in patients with severe, difficult-to-control, nonatopic asthma.
abstract: BACKGROUND
  While up to 50% of patients with severe asthma have no evidence of allergy, IgE has been linked to asthma, irrespective of atopic status. Omalizumab, an anti-IgE monoclonal antibody, is reported to significantly benefit a subset of patients with severe, persistent, allergic asthma. Therefore, we investigated whether omalizumab has biologic and clinical effects in patients with refractory nonatopic asthma.
  
  
  METHODS
  Forty-one adult patients who, despite daily treatment with or without maintenance oral corticosteroids, had severe, nonatopic, refractory asthma according to GINA (Global Initiative for Asthma) step 4, were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary end point was the change in expression of high-affinity IgE receptor (FcεRI) on blood basophils and plasmacytoid dendritic cells (pDC2) after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined.
  
  
  RESULTS
  Compared with placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and pDC2 (P &lt; .001). The omalizumab group also showed an overall increase in FEV1 compared with baseline (+250 mL, P = .032; +9.9%, P = .029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed.
  
  
  CONCLUSIONS
  Omalizumab negatively regulates FcεRI expression in patients with severe nonatopic asthma, as it does in severe atopic asthma. Omalizumab may have a therapeutic role in severe nonatopic asthma. Nonetheless, our preliminary findings support further investigation to better assess the clinical efficacy of omalizumab.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT01007149; URL: www.clinicaltrials.gov and European Clinical Trials Database, EudraCT; No.: 2009-010937-38; URL: https://www.clinicaltrialsregister.eu.
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre; Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Pneumologie, DHU Thorax Innovation, Le Kremlin-Bicêtre; Institut National de la Santé et de la Recherche médicale (INSERM) U999, LabEx LERMIT, Le Plessis Robinson.
authors.forename: Gilles
authors.initials: G
authors.lastname: Garcia
authors.affiliation: Université de Nantes, Faculté de Médecine, Nantes; INSERM U1087, l'institut du thorax, Nantes; France Centre Hospitalier Universitaire de Nantes, l'institut du thorax, service de Pneumologie, Nantes.
authors.forename: Antoine
authors.initials: A
authors.lastname: Magnan
authors.affiliation: Hôpital Arnaud de Villeneuve, Service des Maladies Respiratoires, 34295- Montpellier, Cedex 05.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Chiron
authors.affiliation: Université de Bordeaux, UMR5164, 33076 Bordeaux; CNRS, UMR5164, 33076 Bordeaux; Centre Hospitalier Universitaire de Bordeaux, Laboratoire d'Immunologie, 33076 Bordeaux.
authors.forename: Cécile
authors.initials: C
authors.lastname: Contin-Bordes
authors.affiliation: Universitaire de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC 0005, F-33000 Bordeaux; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC 0005, F-33000 Bordeaux; CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, CIC 0005, F-33604 Pessac.
authors.forename: Patrick
authors.initials: P
authors.lastname: Berger
authors.affiliation: Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares, Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris; INSERM U700, Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris.
authors.forename: Camille
authors.initials: C
authors.lastname: Taillé
authors.affiliation: Service de Pneumologie, Hôpital de la Croix-Rousse, HCL et Université Claude Bernard Lyon1, Villeurbanne.
authors.forename: Gilles
authors.initials: G
authors.lastname: Devouassoux
authors.affiliation: Pôle de Pathologie Thoracique, Hôpitaux Universitaires de Strasbourg, Strasbourg F-67000; Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles-Saint Quentin, Versailles.
authors.forename: Frédéric
authors.initials: F
authors.lastname: de Blay
authors.affiliation: Hopital Foch, Service de Pneumologie, Université Versailles-Saint Quentin, Versailles.
authors.forename: Louis-Jean
authors.initials: LJ
authors.lastname: Couderc
authors.affiliation: Centre Hospitalier Universitaire de Toulouse, Hôpital Larrey, Toulouse F-31059.
authors.forename: Alain
authors.initials: A
authors.lastname: Didier
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre; Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Pneumologie, DHU Thorax Innovation, Le Kremlin-Bicêtre; Institut National de la Santé et de la Recherche médicale (INSERM) U999, LabEx LERMIT, Le Plessis Robinson.
authors.forename: Dermot S
authors.initials: DS
authors.lastname: O'Callaghan
authors.affiliation: Universitaire de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC 0005, F-33000 Bordeaux; Université Bordeaux Segalen, INSERM U657, 33076 Bordeaux.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Girodet
authors.affiliation: Novartis Pharma SAS, Rueil-Malmaison, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourdeix
authors.affiliation: Novartis Pharma SAS, Rueil-Malmaison, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Le Gros
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre; Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Pneumologie, DHU Thorax Innovation, Le Kremlin-Bicêtre; Institut National de la Santé et de la Recherche médicale (INSERM) U999, LabEx LERMIT, Le Plessis Robinson. Electronic address: marc.humbert@bct.aphp.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab; D010919:Placebos; D012129:Respiratory Function Tests; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D000069444:Omalizumab; D007073:Immunoglobulin E