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Original Research: Asthma |

A Proof-of-Concept, Randomized, Controlled Trial of Omalizumab in Patients With Severe, Difficult-to-Control, Nonatopic AsthmaOmalizumab in Severe Nonatopic Asthma

Gilles Garcia, MD, PhD; Antoine Magnan, MD, PhD; Raphaël Chiron, MD; Cécile Contin-Bordes, MD, PhD; Patrick Berger, MD, PhD; Camille Taillé, MD, PhD; Gilles Devouassoux, MD, PhD; Frédéric de Blay, MD, PhD; Louis-Jean Couderc, MD, PhD; Alain Didier, MD, PhD; Dermot S. O’Callaghan, MD; Pierre-Olivier Girodet, MD, PhD; Isabelle Bourdeix, PhD; Vincent Le Gros, MD; Marc Humbert, MD, PhD
Author and Funding Information

From the Université Paris-Sud, Faculté de Médecine (Drs Garcia, O’Callaghan, and Humbert), Le Kremlin Bicêtre; Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Pneumologie, DHU Thorax Innovation (Drs Garcia, O’Callaghan, and Humbert), Le Kremlin-Bicêtre; Institut National de la Santé et de la Recherche médicale (INSERM) U999, LabEx LERMIT (Drs Garcia, O’Callaghan, and Humbert), Le Plessis Robinson; Université de Nantes, Faculté de Médecine (Dr Magnan), Nantes; INSERM U1087, l’institut du thorax (Dr Magnan), Nantes; France Centre Hospitalier Universitaire de Nantes, l’institut du thorax, service de Pneumologie (Dr Magnan), Nantes; Hôpital Arnaud de Villeneuve, Service des Maladies Respiratoires (Dr Chiron), 34295- Montpellier, Cedex 05; Université de Bordeaux (Dr Contin-Bordes), UMR5164, 33076 Bordeaux; CNRS (Dr Contin-Bordes), UMR5164, 33076 Bordeaux; Centre Hospitalier Universitaire de Bordeaux, Laboratoire d’Immunologie (Dr Contin-Bordes), 33076 Bordeaux; Universitaire de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux (Drs Berger and Girodet), U1045, Département de Pharmacologie, CIC 0005, F-33000 Bordeaux; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux (Dr Berger), U1045, CIC 0005, F-33000 Bordeaux; CHU de Bordeaux, Service d’Exploration Fonctionnelle Respiratoire (Dr Berger), CIC 0005, F-33604 Pessac; Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares (Dr Taillé), and INSERM U700 (Dr Taillé), Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris; Service de Pneumologie (Dr Devouassoux), Hôpital de la Croix-Rousse, HCL et Université Claude Bernard Lyon1, Villeurbanne; Pôle de Pathologie Thoracique (Dr de Blay), Hôpitaux Universitaires de Strasbourg, Strasbourg F-67000; Hopital Foch, Service de Pneumologie, Suresnes (Dr Couderc), and Faculté de Médecine Paris-Ile de France-Ouest (Dr de Blay), Université Versailles-Saint Quentin, Versailles; Centre Hospitalier Universitaire de Toulouse, Hôpital Larrey (Dr Didier), Toulouse F-31059; Université Bordeaux Segalen (Dr Girodet), INSERM U657, 33076 Bordeaux; and Novartis Pharma SAS (Drs Bourdeix and Le Gros), Rueil-Malmaison, France.

Correspondence to: Marc Humbert, MD, PhD, Service de Pneumologie et Réanimation Respiratoire, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France; e-mail: marc.humbert@bct.aphp.fr


Funding/Support: This study was supported by Novartis Pharma SAS.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(2):411-419. doi:10.1378/chest.12-1961
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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 < .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.

Trial registry:  ClinicalTrials.gov; No.: NCT01007149; URL: www.clinicaltrials.gov and European Clinical Trials Database, EudraCT; No.: 2009-010937-38; URL: https://www.clinicaltrialsregister.eu

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