Monoclonal antibodies directed against interleukin (IL)-5, such as mepolizumab and benralizumab, are an effective and established treatment for severe eosinophilic asthma. Here, we present a patient with eosinophilic asthma with a partial clinical response to mepolizumab initially, as measured by these biomarkers, who when investigated was found to have refractory airway eosinophilia. Escalation of the mepolizumab dose led to further but still only partial response. A treatment trial with benralizumab was more successful and led to suppression of airway eosinophilia. We review the literature, focusing on eosinophil biology at the tissues and the different mechanisms of action of the two agents.

IntroductionBiomarkers are used to select biologic therapies for patients with severe asthma, but not to regularly adjust therapy, especially oral corticosteroids (OCS).ObjectiveOur goal was to test the efficacy of an algorithm to guide the titration of OCS using blood eosinophil count and fraction of exhaled nitric oxide (FeNO) levels.Design, participants, interventions and settingThis proof-of-concept prospective randomised controlled trial assigned adult participants with severe uncontrolled asthma (n=32) to biomarker-based management (BBM) where OCS dose was adjusted based on a composite biomarker score comprised of blood eosinophil count and FeNO, or a standard best practice (SBP) arm. The study was conducted at the Hunter Medical Research Institute, Newcastle, Australia. Participants were recruited from the local Severe Asthma Clinic and were blinded to their study allocation.Main outcomeThe coprimary outcomes were number of severe exacerbations and time to first severe exacerbation assessed over 12 months.ResultsThere was a longer median time to first severe exacerbation with BBM, although not significant (295 vs 123 days, Adj. HR: 0.714; 95% CI: 0.25 to 2.06; p=0.533). The relative risk of a severe exacerbation in BBM (n=17) vs SBP (n=15) was 0.88 (Adj.; 95% CI: 0.47 to 1.62; p=0.675) with a mean exacerbation rate per year of 1.2 and 2.0, respectively. There was a significant reduction in the proportion of patients requiring an emergency department (ED) visit using BBM (OR 0.09, 95% CI: 0.01 to 0.91; p=0.041). There was no difference in the cumulative OCS dose used between the two groups.ConclusionA treatment algorithm to adjust OCS using blood eosinophil count and FeNO is feasible in a clinical setting and resulted in a reduced odds of an ED visit. This warrants further study to optimise the use of OCS in the future.Trial registration numberThis trial was registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12616001015437).