Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids

Background Asthma is a disease with marked heterogeneity in its clinical course and response to treatment. IL-13 is central to type 2 inflammation, which contributes to many key features of asthma. Lebrikizumab is an anti–IL-13 mAb previously reported to significantly improve lung function in patients with inadequately controlled asthma despite inhaled corticosteroid therapy, especially in periostin-high patients. Objective This phase II study investigated the efficacy and safety of IL-13 blockade with different doses of lebrikizumab in asthmatic patients not receiving inhaled corticosteroids. Methods Patients were randomized to receive 125, 250, or 500 mg of lebrikizumab or placebo subcutaneously monthly for 12 weeks with an 8-week follow-up period. The primary efficacy end point was the relative change in prebronchodilator FEV 1 from baseline to week 12. Results A total of 212 patients were randomized. The mean relative change in FEV 1 was numerically higher in all lebrikizumab dose groups versus the placebo group, although the difference was neither statistically nor clinically significant. There were no meaningful differences in changes in FEV 1 between the dose groups and the placebo group by the periostin subgroup. Lebrikizumab treatment was associated with a reduced risk of treatment failure at all doses versus placebo ( P Conclusion Blocking IL-13, a single cytokine, in this population of asthmatic patients is insufficient to improve lung function. There is evidence that IL-13 blockade may improve disease control, as measured by prevention of protocol-defined treatment failure in these patients.