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Sustained remission was observed in more patients receiving rituximab and concomitant avacopan compared with those treated with concomitant prednisone.
Patients with antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) demonstrated significantly increased remission rate, which was maintained at week 52, in patients in the avacopan group when compared with patients in the prednisone cohort.
Patients in the avacopan cohort also exhibited numerical improvements in remission at week 26, albuminuria, relapse rate, estimated glomerular filtration rate (eGFR), and less glucocorticoid toxicity, according to the study “Efficacy and Safety of Avacopan in Patients with ANCA-Associated Vasculitis Receiving Rituximab in a Phase 3 Trial,” presented at the American College of Rheumatology’s 2023 Convergence in San Diego, California.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 glucocorticoid-tapering schedule. Patients were categorized by ANCA status (either anti-proteinase 3 [PR3] positive or anti-myeloperoxidase positive), vasculitis disease status (relapsing or newly diagnosed), and immunosuppressive treatment (cyclophosphamide [CYC] or RTX).
“American College of Rheumatology (ACR)/Vasculitis Foundation guidelines recommend induction treatment with RTX over cyclophosphamide (CYC),” wrote lead investigator Anisha Dua, MD, MPH, associate professor at Northwestern University, and colleagues. “For relapsing disease, European Alliance of Associations for Rheumatology (EULAR) guidelines recommend RTX.”
The co-primary efficacy endpoints were the proportion of patients able to achieve remission at week 26 and those who were able to achieve sustained remission at week 52. Remission was defined as a Birmingham Vasculitis Activity Score [BVAS] of 0 and no glucocorticoid use for AAV 4 weeks prior to measurement.
Patients were given intravenous RTX 375 mg/m2 once weekly for 4 weeks starting on the first day of the study. Repeated doses of RTX were not included, per the approved labeled regimen at the beginning of the trial.
In total, 330 patients were included in the study, of which 214 (64.8%) were in the RTX stratum. The mean age of patients was 60 years, 76% of patients had renal vasculitis according to BVAS scores, 46% were PR3-ANCA positive, and 58% had newly diagnosed AAV. More (57%) patients in the avacopan cohort were men compared with 48.6% in the prednisone group. eGFR at baseline in the avacopan and prednisone groups was 57.1±32.2 and 56.0±33.4 mL/min/1.73 m2, respectively.
At the 26-week mark, 77.6% (n = 83) of patients in the avacopan group and 75.7% (n = 81) of patients in the prednisone group achieved remission. However, sustained remission was obtained in 71.0% (n = 76) of patients receiving avacopan and 56.1% (n = 60) of those treated with prednisone at week 52.
Serious treatment-emergent adverse events (TEAEs) were observed in 34.6% (n = 37, 62 total events) of those the avacopan cohort compared with 39.3% (n = 42, 91 total events) in the prednisone group. The relapse rate was lower in those treated with avacopan (8.7%, n = 9) compared with prednisone (20.2%, n = 21). Improvements were also observed in glucocorticoid-associated toxicity and albuminuria for patients in the avacopan cohort.
“These results demonstrate the efficacy of avacopan for achieving and sustaining remission in patients with AAV treated with RTX,” investigators concluded.