Targeted Therapy of Severe Asthma: Switching of Biologicals in Real Clinical Practice – Causes and Consequences

Abstract

BACKGROUND: complexity of choice a genetically engineered biological drug (GEBD) for severe bronchial asthma (SA) treatment is due to intersection of endotypes and phenotypes of the disease. Mistakes in biologicals choice lead to discontinuation and/or switching of the drug due to insufficient effectiveness of therapy. AIMS: to determine reasons to stop targeted therapy and biologicals switching effectiveness in patients with SA in real clinical practice. MATERIALS AND METHODS: analyzed patients with SA (n=116) from Sverdlovsk region register were divided into 3 groups (#1-continuous, #2-stoppers and #3-switched). Predictors of biologicals withdrawal and switching, reasons for the 1st biological stopping, switching schemes, therapy effectiveness after switching (according to ACT, FEV1, AQLQ, SNOT-22, the need for SGCS, achievement of SA remission) were determined. RESULTS: There were 17.2% stopping and 12.1% switching patients out of 116 patients in the registry. Stoppers suffered from CRSwNP less often and had earlier asthma onsets. Switched patients had higher blood eosinophils level. Therapy was cancelled for personal reasons in 45% of patients. Therapys ineffectiveness in SA and/or in CRSwNP was the main reason for switching (92.8%) mostly from omalizumab and benralizumab. The switch drug of choice was dupilumab. Improved indicators: ACT (by 86.4%), FEV1 (by 21.2%), AQLQ (by 52.5%), SNOT-22 (by 48%), the need for SGCS decreased to 0 in 12 months after switching. Remission was achieved in 62.5% of patients (excluding FEV1) and 50% of patients (including FEV1). CONCLUSIONS: Careful selection of targeted therapy patients allows to minimize the failures of the starting drug to 12.1%. Switching the starting GEBD, aimed only at blocking eosinophils or only at blocking IgE, due to its inefficiency, to a drug with a dual mechanism of action leads to a significant improvement in ACT, FEV1, AQLQ, SNOT-22 and absence of SGCS need.