Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) showed a significant increase in remission sustained at week 52 in the avacopan group compared with patients in the prednisone cohort.
Patients in the Avacopan cohort also demonstrated numerical improvements in remission at week 26, albuminuria, relapse rate, estimated glomerular filtration rate (eGFR), and less glucocorticoid toxicity, according to “Efficacy and Safety of Avacopan in Patients with ANCA-A.” Getting Rituximab in a Phase 3 Trial,” presented at the American College of Rheumatology 2023 Convergence in San Diego, CA.1:
In the randomized, double-blind, double-dummy, controlled phase 3 ADVOCATE trial, investigators evaluated whether avacopan, an oral selective C5a receptor inhibitor, could replace a tapering schedule of glucocorticoids. Patients were stratified by ANCA status (or anti-protein 3 [PR3] positive or antimyeloperoxidase positive), vasculitis disease status (recurrent or newly diagnosed), and immunosuppressive treatment (cyclophosphamide). [CYC] or RTX).
“The American College of Rheumatology (ACR)/Vasculitis Foundation guidelines recommend induction treatment with RTX over cyclophosphamide (CYC),” wrote lead researcher Anisha Duan, MD, MPH, associate professor at Northwestern University, and colleagues. “In relapsed disease, the European Alliance of Rheumatology Associations (EULAR) guidelines recommend RTX.
The co-primary efficacy endpoints were the proportion of patients who achieved remission at week 26 and those who achieved sustained remission at week 52. Remission was defined as Birmingham Vasculitis Activity Score. [BVAS] 0 and glucocorticoid use for AAV 4 weeks prior to measurement.
Patients received intravenous RTX 375 mg/m2 once weekly for 4 weeks starting on study day 1. Repeat doses of RTX were not included according to the off-label regimen approved at the start of the trial.
A total of 330 patients were included in the study, of which 214 (64.8%) were in the RTX group. The median age of patients was 60 years, 76% of patients had renal vasculitis as assessed by BVAS, 46% were PR3-ANCA positive, and 58% had newly diagnosed AAV. More (57%) patients in the avacopan group were male compared with 48.6% in the prednisone group. eGFR at baseline was 57.1±32.2 and 56.0±33.4 mL/min/1.73 m2 in the avacopan and prednisone groups, respectively.
At the 26-week mark, 77.6% of patients in the avacopan group (n = 83) and 75.7% of patients in the prednisone group (n = 81) achieved remission. However, sustained remission was achieved in 71.0% (n = 76) of patients receiving avacopan and 56.1% (n = 60) of those treated with prednisone at week 52.
Treatment-emergent serious adverse events (TEAEs) occurred in 34.6% (n = 37, 62 total events) in the avacopan group compared with 39.3% (n = 42, 91 total events) in the prednisone group. Relapse was lower in those treated with avacopan (8.7%, n = 9) compared with prednisone (20.2%, n = 21). Improvements were also seen in glucocorticoid-related toxicity and albuminuria in patients in the avacopan group.
“These results demonstrate the efficacy of avacopan in achieving and maintaining remission in patients with AAV treated with RTX,” the researchers concluded.
- Duvuru G, DuaA, YueH, SalvaraniC, etc. Efficacy and Safety of Avacopan in Patients with ANCA-Associated Vasculitis Receiving Rituximab in a Phase 3 Trial. Presented at: American College of Rheumatology Convergence 2023: San Diego, CA. November 10-15, 2023
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