Add-on belimumab does not reduce relapse risk in ANCA-associated vasculitis
medwireNews: The addition of belimumab to maintenance therapy with azathioprine and low-dose glucocorticoids does not improve maintenance of remission among patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), findings from the BREVAS trial suggest.
The phase III study included 105 patients in AAV remission, of whom 27 received induction therapy with rituximab and 78 with cyclophosphamide, both given alongside high-dose glucocorticoids.
As reported in Arthritis & Rheumatology, the primary endpoint of the study was a composite of Birmingham Vasculitis Activity Score (BVAS) of at least 6 points, at least one major BVAS item, and receipt of a non-study medication (including immunomodulatory investigational agents, rituximab, cyclophosphamide, other immunosuppressive agents, and glucocorticoids <10 mg/day).
Over the study period, this endpoint occurred in 18.9% of the 53 patients who were randomly assigned to receive intravenous belimumab 10 mg/kg every 28 days alongside maintenance therapy with azathioprine (2 mg/kg per day) and low-dose oral glucocorticoids (≤10 mg/day).
This was not significantly different from the 21.2% rate for the 52 patients who were allocated to receive placebo alongside maintenance azathioprine and low-dose glucocorticoids, say the BREVAS (Belimumab in Remission of Vasculitis) investigators.
They add that the median time to occurrence of the composite endpoint did not significantly differ among the belimumab and placebo groups (162 vs 95 days), and a comparable proportion of patients in both groups experienced a vasculitis relapse (BVAS ≥6, ≥1 BVAS major item, or the receipt of prohibited medications for the treatment of vasculitis; 11.3 vs 15.4%).
However, the researchers found that none of the 14 patients with rituximab-induced remission who subsequently received belimumab experienced vasculitis relapse, whereas vasculitis relapses were “evenly distributed across different induction regimens” in the placebo group, a finding that they say “warrants further investigation.”
Peter Merkel (University of Pennsylvania, Philadelphia, USA) and colleagues caution that their study, conducted between 2013 and 2017, had “a number of recruitment difficulties, primarily relating to the advancement of standard of care treatment options, including the licensing of rituximab for the treatment of AAV,” and therefore “consists of a small sample size with reduced power for the primary outcome analysis.”
Moreover, the study design was changed from being event-driven to having a fixed completion date 12 months after the final participant was recruited, which the team says led to “variable durations of treatment.” The median follow-up time was not reported.
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