Chest. 2013 Apr 11. doi: 10.1378/chest.12-1961. [Epub ahead of print]

A proof of concept randomized-controlled trial of omalizumab in patients with severe difficult to control nonatopic asthma.

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