Compared with placebo, the interleukin-13-neutralizing human monoclonal antibody tralokinumab did not have a significant effect on eosinophilic airway inflammation in moderate to severe asthma that was inadequately controlled on inhaled corticosteroids, according to a study published in The Lancet Respiratory Medicine.
This 12-week double-blind, randomized, placebo-controlled phase 2 trial included 224 male and female study participants between ages 18 and 75 who were recruited from 15 separate centers across Canada, Denmark, and the United Kingdom. All participants had a history of moderate to severe asthma treated with a stable dose of inhaled corticosteroids without other asthma medications, and only 79 of the 224 participants met eligibility criteria after the 4-week run-in period.
After the run-in period, participants were randomly enrolled in 12 weeks of treatment with tralokinumab 300 mg (n=39) or placebo (n=40). The primary study outcome was the change from baseline of eosinophil count, determined by bronchial biopsy. Secondary study outcomes were change from baseline in blood and sputum eosinophil counts. Fractional exhaled nitric oxide (FENO) concentrations and blood immunoglobulin E concentrations from baseline were exploratory outcomes.
Treatment with tralokinumab had no significant effect on eosinophilic inflammation, but it did lead to significant reductions in blood immunoglobulin E (treatment effect ratio 0.86, 95% CI, 0.77-0.97; P =.014), and FENO concentrations (treatment effect ratio 0.78, 95% CI, 0.63-0.96; P =.023).
Study investigators concluded, “Benefits in lung function observed in previous studies, and small improvements in markers of both large and small airway function observed in this study are independent of eosinophilic inflammation and might be a consequence of effects of interleukin 13 on airway smooth muscle. We recommend further bronchoscopic and imaging studies of novel therapies for severe asthma, which we anticipate will provide greater insights into the mechanisms of this disease.”
Disclosures: This trial was supported by AstraZeneca.
Russell RJ, Chachi L, FitzGerald JM, et al; on behalf of the MESOS study investigators. Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial [published online May 21, 2018]. Lancet Respir Med. doi:10.1016/S2213-2600(18)30201-7