A proof of concept randomized-controlled trial of omalizumab in patients with severe difficult to control nonatopic asthma.
Chest. 2013 Apr 11;
Authors: Garcia G, Magnan A, Chiron R, Contin-Bordes C, Berger P, Taillé C, Devouassoux G, de Blay F, Couderc LJ, Didier A, O'Callaghan DS, Girodet PO, Bourdeix I, Le Gros V, Humbert M
ABSTRACT BACKGROUND While up to 50% of severe asthma patients have no evidence of allergy, immunoglobulin E (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. We therefore investigated whether omalizumab has biological and clinical effects in patients with refractory nonatopic asthma. METHODS Forty-one adult patients with severe nonatopic refractory asthma despite daily treatment according to GINA step 4 with or without maintenance oral corticosteroids were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary endpoint was the change in expression of high-affinity IgE receptor (FcεRI) on blood basophils and plasmacytoid dendritic cells after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined. RESULTS Compared to placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and plasmacytoid dendritic cells (p<0.001). The omalizumab group also showed an overall increase in FEV1 compared to baseline (+250 ml; p=0.032, +9.9%; p=0.029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed. CONCLUSION 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. CLINICAL TRIAL REGISTRATION Registered as ClinicalTrials.gov (identifier: NCT01007149) and European Clinical Trials Database, EudraCT (identifier: 2009-010937-38).
PMID: 23579324 [PubMed - as supplied by publisher]