Efficacy and safety of belimumab and azathioprine for maintenance of remission in ANCA-associated vasculitis: a randomized controlled study

Objective To evaluate safety and efficacy of belimumab as adjunctive therapy to maintain remission in antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV). Methods This double‐blind, placebo‐controlled, multicenter study (BEL115466/NCT01663623) randomized (1:1) patients (≥18 years) with AAV following remission induction with rituximab/cyclophosphamide and glucocorticoids. Patients received azathioprine 2 mg/kg/day, oral glucocorticoids, and placebo/intravenous belimumab 10 mg/kg. Primary endpoint was time to first protocol‐specified event (PSE), defined as Birmingham Vasculitis Activity Score (BVAS) ≥6, ≥1 major BVAS item, or receipt of prohibited medication (adjusted for ANCA type [proteinase 3 (PR3)/myeloperoxidase (MPO)], disease stage at induction, and induction regimen). Vasculitis relapse was defined as PSE BVAS activity, or receipt of prohibited medications for vasculitis. Changes in treatment practice led to study truncation from 300 to ~100 patients. Results The intention‐to‐treat population totaled 105 patients (placebo, 52 [40 PR3‐ANCA; 12 MPO‐ANCA]; belimumab, 53 [41 PR3‐ANCA; 12 MPO‐ANCA]: induced by rituximab, 27; cyclophosphamide, 78. Compared with placebo, belimumab did not reduce PSE risk (adjusted HR=1.07; 95% CI: 0.44, 2.59; p=0.884) or vasculitis relapse (adjusted HR=0.88; 95% CI: 0.29, 2.65; p=0.821); overall PSE rate was low (placebo, 11/52 [21.2%]; belimumab 10/53 [18.9%]). Vasculitis relapse in the placebo group (n=8) occurred independently of induction regimen/disease stage, or ANCA type. All vasculitis relapses in the belimumab group (n=6) were in cyclophosphamide‐induced, anti‐PR3‐ANCA‐associated patients. Adverse events occurred in 49/53 belimumab (92.5%) and 43/52 placebo (82.7%) recipients, with no new safety concerns. Conclusion Belimumab plus azathioprine and glucocorticoids for the maintenance of remission in AAV did not reduce risk of relapse