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

Abstract

AstraZeneca.

Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials

“…In that study, tralokinumab treatment was associated with improvements in airway physiology but no effect was observed upon airway inflammation. 25 In contrast, dupilumab, an anti-IL-4 receptor α monoclonal antibody that targets both IL-4 and IL-13 signalling, has demonstrated significant reductions in exacerbations in people with uncontrolled, persistent asthma. 26,27 It's possible this difference is because dupilumab is able to reduce airway inflammation whilst tralokinumab cannot, but there is currently no evidence that this is the case.…”

“…26 The increase in blood eosinophils observed with anti-IL-13 therapy has been hypothesised to be the result of reduced recruitment of eosinophils to the lungs from the blood, 37 but the MESOS results have suggested this does not occur. 25 Interestingly, dupilumab is the only developmental biologic agent for the treatment of asthma that both reduces exacerbations and increases blood eosinophils. 26 Approved agents for severe asthma such as corticosteroids and the biologics omalizumab (anti-IgE), benralizumab (anti-IL-5 receptor α), mepolizumab and reslizumab (both anti-IL-5), reduce eosinophil counts during therapy and reduce exacerbation rates in participants with severe asthma.…”

Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline

“…An obvious example is the anti-IL-13 monoclonal tralokinumab [79,80]. At least three randomised controlled studies in adults failed to show significant clinical efficacy [81][82][83] and there are no plans to do a paediatric trial, on the basis that the data show that the IL-13 pathway is not crucial in airway eosinophilia. It is true that adolescents age >12 years are included in these studies, but the actual numbers enrolled are dwarfed by adult participants.…”

ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

“…Anti-IL-4R: dupilumab Dupilumab reduced severe exacerbations in all-comers irrespective of their atopic status, with the greatest reduction in those with elevated F ENO and/or eosinophilic inflammation, and reduced OCS requirement for severe asthmatics receiving maintenance OCS [68,217,218]. Studies of IL-4 inhibition alone, and more recently of the anti-IL-13 biologicals lebrikizumab [219] and tralokinumab [220], have failed to meet their primary end-points of exacerbation reduction, suggesting that inhibition of both IL-4 and -13, as with anti-IL-4R, is necessary to observe sufficient clinical efficacy for this aspect of the disease.…”