Omalizumab in Severe Asthma: Effect on Oral Corticosteroid Exposure and Remodeling. A Randomized Open-Label Parallel Study.

Abstract

Data on the clinical efficacy and remodeling of omalizumab therapy in patients on oral corticosteroids (OC) are limited. The purpose of the study is to show that in patients with corticosteroid-dependent asthma, omalizumab is a corticosteroid-sparing therapy able to inhibit airway remodeling and to reduce disease burden (lung function impairment, exacerbations). This study is a randomised open-label study evaluating the addition of omalizumab to the standard of care in patients with severe asthma receiving oral corticosteroids. The primary endpoint was represented by the change in OC monthly dose by the end of treatment and secondary endpoints included spirometry changes, airway inflammation (FeNO), number of exacerbations and airways remodelling assessed by bronchial biopsies studied by transmission electron microscopy. As a safety variable, adverse effects were recorded. Efficacy was assessed for 16 patients in the omalizumab group and 13 in the control group. The final cumulative mean monthly OC doses were 34.7mg and 217mg for the omalizumab and control group, respectively; the mean difference between groups adjusted for baseline was -148.1 [95% confidence interval (CI) -243.6, -52.5; p=0.004]. OC withdrawal of 75% versus 7.7% (p=0.001) was observed in the omalizumab and control group, respectively. Omalizumab provided a slowing of forced expiratory volume in one second (FEV1) loss (70 mL versus 260 mL), a significant decrease in FeNO values and a reduction in the annual relative risk of clinically significant exacerbations of 54%. The treatment was well tolerated. The morphological study showed a significant decrease in basement membrane thickness in the omalizumab group (6.7µm versus 4.6µm) compared with controls (6.9µm versus 7µm) [mean difference between groups adjusted for baseline was -2.4 (95% CI -3.7, -1.2; p<0.001], as well as a decrease in intercellular spaces (1.18µm versus 0.62µm and 1.21µm versus 1.20µm, p=0.011, respectively). A qualitative improvement was also observed in the treated group. Omalizumab showed a marked OC-sparing capacity and was associated with an improvement in clinical management that correlated with bronchial epithelial repair. In OC-dependent asthma, reversibility of remodelling is possible; the concepts that basement membrane enlargement is detrimental and that chronic airway obstruction is systematically irreversible are outdated (EudraCT: 2009-010914-31).