Clinical and functional profile of patients with severe eosinophilic asthma with rapid response to benralizumab therapy (super-responders): a single-center retrospective study

BACKGROUND: Benralizumab therapy in severe eosinophilic bronchial asthma demonstrates a heterogeneous clinical response. The identification of a group of patients who rapidly achieve clinical remission (super responders) and the analysis of their initial characteristics are necessary for the personalization of biological therapy.

AIM: to characterize the clinical and functional profile of patients with a rapid positive response to benralizumab therapy (super-responders) within 4–6 months.

METHODS: A single-center retrospective observational study was conducted. The analysis included 45 adult patients with uncontrolled severe asthma and a baseline blood eosinophil count >300 cells/μL who received benralizumab in real-world clinical practice for 4–6 months. Super-response was defined as the simultaneous achievement of four criteria after 4–6 months of benralizumab therapy: no exacerbations, discontinuation of maintenance systemic glucocorticosteroids, an Asthma Control Test score ≥20, and an increase in pre-bronchodilator forced expiratory volume in 1 second of ≥100 mL. Baseline demographic, clinical, laboratory, and functional characteristics and their changes over time were assessed.

RESULTS: 8 (17.8 %) out of 45 patients met the super-response criteria. Compared with the rest of the participants, the super responders were characterized by a statistically significantly shorter duration of asthma (median 6.0 years versus 16.0 years, p = 0.019), a higher baseline control level according to Asthma Control Test (median 17.0 points versus 10.0 points, p = 0.009) and a better quality of life according to Asthma Quality of Life Questionnaire (median 143.5 points versus 113.0 points, p = 0.020). With concomitant chronic polypous rhinosinusitis in the group of super responders, the initial severity of symptoms according to Sino-Nasal Outcome Test-22 was lower (p = 0.004). There were no statistically significant intergroup differences in the baseline level of peripheral blood eosinophils, the fraction of nitric oxide in exhaled air, total immunoglobulin E, and respiratory function parameters. In the general cohort (n = 45), after 4–6 months of therapy, there was a significant improvement in asthma control (Asthma Control Test, Asthma Control Questionnaire-5), quality of life (Asthma Quality of Life Questionnaire), forced expiratory volume in 1 second, and a decrease in fraction of nitric oxide in exhaled air (in all cases, p < 0.05). In one-factor logistic regression models, the initial Asthma Control Test variables demonstrated a statistically significant association with the presence of a super-response (odds ratio 1.379; 95 % confidence interval 1.082–1.758; p = 0.009), Asthma Control Questionnaire-5 (odds ratio 0.355; 95 % confidence interval 0.148–0.850; p = 0.02), Asthma Quality of Life Questionnaire (odds ratio 1.035; 95 % confidence interval 1.006–1.065; p = 0.017), while Asthma Control Test is the strongest predictor of the super-response of the three presented (area under curve 0.794; average precision 0.661; sensitivity 50.0 %; specificity 100.0 %; positive predictive value (precision) 100.0 %; negative predictive value 66.7 %). No adverse events were reported during benralizumab therapy.

CONCLUSION: Patients with severe eosinophilic bronchial asthma with a super-response to benralizumab therapy were characterized by a shorter disease duration and better initial symptom control, while markers of T2 inflammation (blood eosinophils, fraction of nitric oxide in exhaled air) did not demonstrate a statistically significant association with the presence of a super-response (p >0.05). The predictors of achieving a super-response were a higher initial score on Asthma Control Test and Asthma Quality of Life Questionnaire and a lower score on Asthma Control Questionnaire-5. The data obtained may contribute to the earlier initiation of anti-IL-5Rα therapy and the prediction of the expected clinical response.