Flavia Cecilia Lega Hoyte

The introduction of biologics, such as benralizumab (an anti‐IL‐5 receptor α humanised monoclonal antibody), has made remission a feasible goal for patients with severe eosinophilic asthma (SEA). However, there are remaining research gaps and no clear consensus on the definition of remission. We consolidated post hoc remission data from clinical trials and real‐world studies of benralizumab in patients with SEA to gather insights on: testing different definitions; predictors of remission; the effect of comorbidities on achieving remission; remission and background medication reduction; long‐term remission patterns with benralizumab; and remission in a real‐life setting. In the SIROCCO and CALIMA Phase 3 randomised studies, patients with remission had higher baseline median blood eosinophil counts, were more likely to have a FEV ₁ of ≥ 65% predicted, had fewer exacerbations within 12 months and had lower mean ACQ‐6 scores. Compared with the overall population, patients with a history of nasal polyps were also more likely to achieve remission with benralizumab. Analyses of the BORA and MELTEMI extension studies showed that in the longer term, once remission is achieved with benralizumab, patients are likely to remain in remission with continued treatment. In the open‐label, single‐arm ANDHI‐In Practice and PONENTE studies, patients achieving remission had a shorter median time since asthma diagnosis, higher median age at asthma onset and lower median ACQ‐6 scores. The SHAMAL study and the Phase 3b ANDHI‐In Practice substudy demonstrate that remission is maintained with benralizumab even when patients reduce their background medication. Finally, the XALOC‐1 real‐world study highlights how patients with lower BMI are more likely to achieve remission with benralizumab. These findings demonstrate that achieving remission in patients with SEA is feasible with benralizumab and, in turn, inform future directions for research and treatment that includes a promising shift towards a new era of treat‐to‐target. This manuscript was supported by AstraZeneca, the manufacturer of benralizumab.

Introduction Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2 years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes. Methods Patients (aged 12–80 years) with severe, uncontrolled asthma were randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. SNOT-22 total, domain, and item scores were assessed in patients with a history of CRSwNP. Annualized asthma exacerbation rate (primary efficacy outcome), pre-bronchodilator forced expiratory volume in 1 s, and Asthma Control Questionnaire-6, Asthma Quality of Life Questionnaire (standardized) for patients 12 years and older, and Asthma Symptom Diary scores were also assessed in patients with and without a history of CRSwNP. Results Of 1059 patients with severe asthma, 165 (15.6%) had a history of CRSwNP. Tezepelumab treatment resulted in sustained improvements versus placebo in SNOT-22 total score throughout the 52-week study period [least-squares mean difference (95% confidence interval) − 11.08 (− 17.80, − 4.35)]. Tezepelumab improved all five SNOT-22 domain scores (sleep, nasal, function, ear/facial, and emotion) and the five SNOT-22 item scores of most clinical interest (decreased sense of smell/taste, nasal blockage, reduced productivity, waking up tired, and cough). Tezepelumab improved asthma-related clinical outcomes in patients with and without a history of CRSwNP. Conclusion In patients with severe, uncontrolled asthma and a history of CRSwNP, tezepelumab improved rhinosinusitis symptoms across multiple domains, as well as asthma exacerbations, lung function, asthma control, and health-related quality of life. ClinicalTrials.gov Identifier NCT03347279 (https://classic.clinicaltrials.gov/ct2/show/NCT03347279).