Background/Purpose: GPA (Wegener’s) and MPA are organ- and life-threatening systemic vasculitides characterized by the presence of ANCA-associated vasculitis (AAV), implicating B cells in disease pathogenesis. This study investigated the efficacy and safety of belimumab (BEL), a monoclonal antibody that inhibits B lymphocyte stimulator, in addition to standard of care, for the maintenance of remission in AAV following a standard induction regimen.

Methods: This multicenter, double-blind study (BEL115466/NCT01663623) randomized (1:1) patients (≥18 years) with GPA or MPA in remission (Birmingham Vasculitis Activity Score [BVASv3] = 0 plus prednisolone ≤10 mg/day or equivalent) following prior induction with CYC or RTX for new or relapsing disease. Patients received azathioprine (AZA) 2 mg/kg/day, and oral glucocorticoids, plus either intravenous BEL 10 mg/kg or placebo (PBO) (Days 0, 14, 28, and every 28 days thereafter until study completion [12 months after last patient randomized]). The primary endpoint was time to first relapse, defined as ≥1 major BVAS item, total BVAS score ≥6, or receipt of prohibited medications resulting in treatment failure. Adverse events (AE) were monitored. The study was truncated from 300 to 105 patients due to changes in conventional treatment practice.

Results: When the study stopped, of 105 patients in the intent-to-treat population, 76 continued for ≥1 year, 21 for ≥2 years, and 2 for ≥3 years. Baseline data:

There was no significant difference in time to first relapse between treatment groups: adjusted hazard ratio (95% confidence interval), 1.07 [0.44, 2.59]; p=0.884. Among patients who relapsed (BEL, 10 [19%]; PBO, 11 [21%]), median (range) time to first relapse was 162 (1–371) days for BEL and 95 (15–789) days for PBO. For patients induced with RTX there were 0/1 relapses classified as vasculitis related in the BEL group versus 3/4 in the PBO group. In CYC-induced patients there were 6/9 versus 5/7 vasculitis relapses, respectively. At the final visit (double-blind) most patients were in remission (BEL, 40 [82%]; PBO, 40 [87%]).

AEs were reported in 49 (93%) BEL and 43 (83%) PBO patients post baseline. The most common AE category was infection (BEL, 30 [57%]; PBO, 30 [58%]). Serious AEs (SAEs) occurred in 18 (34%) BEL and 16 (31%) PBO patients; the most common category was infection (BEL, 4 [8%]; PBO, 4 [8%]).  

Conclusion: In patients with AAV who were in remission, the addition of BEL to maintenance therapy with AZA and oral glucocorticoids did not reduce risk of relapse. RTX-induced patients exhibited numerically fewer relapses of vasculitis with treatment with belimumab compared with placebo, warranting further investigation. Overall relapse rate was low (21/105 [20%]). No new safety signals were identified for BEL in the overall population.

Study funded/conducted by GSK. Editorial assistance: Sam Halliwell, PhD, Fishawack Indicia Ltd, funded by GSK