Tralokinumab unsuccessful for management of severe, uncontrolled asthma

In the past decade, substantial efforts have been made to develop therapies based on biologics, particularly those targeting type 2 immune cytokines such as interleukins 4, 5, and 13, and as a result of these efforts, anti-interleukin-5 and anti-interleukin-5 receptor-α antibodies for the treatment of severe eosinophilic asthma are now available. 1 Chung KF Targeting the interleukin pathway in the treatment of asthma. Lancet. 2015; 386: 1086-1096 Summary Full Text Full Text PDF PubMed Scopus (190) Google Scholar Interleukin 13—a cytokine produced by T-helper 2 lymphocytes, type-2 innate lymphoid cells, mast cells, and eosinophils—has been implicated in the pathogenesis of asthma with its ability to induce goblet cell hyperplasia, lung eosinophilia, and bronchial hyper-responsiveness, in addition to its contribution to airway wall remodelling. 2 Hirose K Iwata A Tamachi T Nakajima H Allergic airway inflammation: key players beyond the Th2 cell pathway. Immunol Rev. 2017; 278: 145-161 Crossref PubMed Scopus (85) Google Scholar It is therefore not surprising that interleukin 13 has been considered as another target for the treatment of asthma associated with type 2 inflammation. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trialsTralokinumab reduced AAER in participants with severe asthma with baseline FENO 37 ppb or higher in STRATOS 1, but not in STRATOS 2. These inconsistent effects on AAER do not support a key role for interleukin 13 in severe asthma exacerbations. Full-Text PDF 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 trialTralokinumab did not significantly affect eosinophilic inflammation in bronchial submucosa, blood, or sputum compared with placebo, but did reduce FENO and IgE concentrations. These results suggest interleukin 13 is not crucial for eosinophilic airway inflammation control in moderate-to-severe asthma. Full-Text PDF