P98 Steroid-sparing effects of benralizumab in patients with eosinophilic granulomatosis with polyangiitis

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, ANCA-associated vasculitis characterised by asthma, chronic rhinosinusitis and blood eosinophilia which may be accompanied by neurological, cardiac, cutaneous and renal involvement. Interleukin-5 (IL-5) is a key cytokine implicated in eosinophil survival. We present our experience with benralizumab, a humanised monoclonal antibody that interferes with the IL-5 receptor alpha (IL-5Rα), and its effect on patient-reported outcomes and oral corticosteroid (OCS) requirements. Methods Patients with established EGPA and on OCS maintenance therapy were commenced on benralizumab 30 mg administered by subcutaneous injections. Patient reported outcomes were assessed by the Birmingham Vasculitis Activity Score (BVAS) and the the Asthma Control Questionnaire (ACQ). OCS dose, lung function, blood eosinophil count and exacerbation rate were recorded at baseline, 24 weeks and 48 weeks of treatment. Results Eleven patients (6 female) with a mean age of 50±14 years completed 24 weeks of treatment; nine completed 48 weeks. A significant improvement in BVAS from baseline 7.91 (±3.27) to 3.45 (±2.52) at 24 weeks (p=0.0001) and 3.44 (±2.88) at 48 weeks (p=0.0007) was recorded. The ACQ changed from baseline 2.13 (±0.98) to 1.73 (±1.57) at 24 weeks (p = 0.47) and 1.03 (±0.71) at 48 weeks (p=0.012). After 24 weeks, there was a median reduction in OCS of 50%; 8/11 (73%) patients were able to reduce their dose by ³ 50%. After 48 weeks, the median reduction in mOCS was 65% and 8 (89%) were able to reduce their dose by ≥ 50%. The median prednisolone dose was reduced from 15 (IQR 10–20) mg to 5 (IQR 5–10) mg at 24 weeks and 5 (IQR 1–6.5) mg at 48 weeks (p = 0.0018) (figure 1). No significant changes were observed in lung function. Eosinophil counts were totally depleted. No increase in exacerbations was seen. Benralizumab was well tolerated and no adverse effects were recorded. Conclusion We report significant reductions in mOCS requirements and improved measures of disease control following benralizumab therapy in patients with EGPA. Further research exploring the mechanism(s) of residual disease in eosinopaenic patients is needed and will compliment upcoming prospective controlled trials of this therapy in EGPA.