S54 Evidence of drug antibody development in severe eosinophilic asthmatics treated with benralizumab. (12th November 2019) - Thomson, L
Abstract : Introduction: Benralizumab is an anti-IL5R monoclonal antibody (mAb) approved for the treatment of severe eosinophilic asthma (SEA). In phase 3 trials, 13%-15% of subjects developed anti-drug antibodies to benralizumab, however, study investigators reported no associated adverse clinical outcomes. Benralizumab fully depletes blood eosinophils in the vast majority of cases and a sudden rise in the blood eosinophil count on treatment can be used as a biomarker of antibody development. To date, no real-world data exists on the incidence of drug antibody development with benralizumab and whether any loss of clinical efficacy is observed. Methods: We conducted a retrospective review of all patients with SEA who had completed at least 12 weeks of treatment with benralizumab. As it was not possible to obtain the benralizumab drug antibody assay we identified those who had a rise in their blood eosinophil count to ≥0.1 x 10 9 cells on treatment. Baseline characteristics and any evidence of loss of clinical efficacy was recorded. Results: A total of 134 patients treated with benralizumab for SEA were identified. The median duration of treatment was 40 weeks (24–48). Having had undetectable blood eosinophils at the time of the second benralizumab dose, 13/134 (9.7%) patients (mean age 44.8±6.0, 5/13 female) subsequently had a rise in their blood eosinophils to ≥0.1 x 10 9 cells during treatment. The median peak eosinophil count on treatment in these patients was 0.40 (IQR 0.20–1.00). The median time to detectable eosinophils was 24 weeks (IQR 16–24). Median time to exacerbation after detectable eosinophils was 8 weeks (IQR 4–12). ACQ-reduced by 0.26±1.13 from baseline in this cohort. This compares to an improvement of 0.88±1.56 in our entire benralizumab cohort. 8/13 patients discontinued benralizumab due to loss of clinical efficacy and were switched to an alternative biologic therapy. Conclusion: In a large cohort of 134 SEA patients treated with benralizumab we report the first real-world evidence of possible antibody development in approximately 10% of patients. This was associated with an objective clinical decline in asthma control and/or acute exacerbation necessitating a switch of treatment in 62% of patients.