Targeted Therapy for Severe Asthma: Switching Biological agents in Real Clinical Practice — Causes and Consequences

BACKGROUND: The complexity of choosing a genetically engineered biological drug for the treatment of severe bronchial asthma is due to the intersection of disease endotypes and phenotypes. Mistakes in biological choice lead to the discontinuation and/or switching of the drug because of insufficient effectiveness of therapy.

AIM: To determine the reasons for stopping targeted therapy and biological switching effectiveness in patients with severe bronchial asthma in clinical practice.

MATERIALS AND METHODS: Patients with severe bronchial asthma (n=116) from the Sverdlovsk region register were divided into three groups: (1) continuous, (2) stoppers, and (3) switchers. Predictors of biological withdrawal and switching, reasons for the first biological stopping, switching schemes, therapy effectiveness after switching according to the asthma control test (ACT), asthma quality of life questionnaire (AQLQ), 22-item sinonasal outcome test [SNOT-22], forced expiratory volume in the first second, need for systemic glucocorticosteroids, and achievement of strong asthma control were determined.

RESULTS: Of the 116 patients in the registry, 17.2% were stoppers and 12.1% were switchers. Stoppers suffered from chronic rhinosinusitis with nasal polyps less often and had an earlier asthma onset. Switchers had higher blood eosinophil levels. Therapy was canceled for personal reasons in 45% of the patients. The ineffectiveness of therapy in severe bronchial asthma and/or chronic rhinosinusitis with nasal polyps was the main reason for switching (92.8%) from omalizumab and benralizumab. The drug of choice for switching was dupilumab. Indicators improved, namely, ACT by 86.4%, AQLQ by 52.5%, SNOT-22 by 48%, and forced expiratory volume in the first second by 21.2%), and the need for systemic glucocorticosteroids decreased to 0 in 12 months after switching. Strong control was achieved in 62.5% of the patients when excluding the forced expiratory volume in the first second, and 50% of patients when including the forced expiratory volume in the first second.

CONCLUSION: Careful selection of targeted therapy patients minimizes the failures of the starting drug to 12.1%. Switching the starting genetically engineered biological drug, aimed only at blocking eosinophils or only at blocking IgE, because of its inefficiency, to a drug with a dual mechanism of action leads to a significant improvement in ACT, AQLQ, SNOT-22, forced expiratory volume in the first second, and absence of systemic glucocorticosteroids.