Patients with antineutrophil cytoplasmic antibody (AAV)-associated vasculitis treated with rituximab (RTX) showed a significantly increased remission rate, which was sustained at week 52, in patients in the avacopan group compared with patients in the prednisone cohort.
Patients in the avacopan cohort also showed numerical improvements in week 26 remission, albuminuria, relapse rate, estimated glomerular filtration rate (eGFR), and less glucocorticoid toxicity, according to the Efficacy and Safety of Avacopan in Patients with ANCA-Associated Vasculitis Relapse study. 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 the glucocorticoid tapering schedule. Patients were categorized according to ANCA status (or 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 (CIC), wrote lead researcher Anisha Dua, MD, MPH, associate professor at Northwestern University, and colleagues. For relapsing disease, the European Alliance of Rheumatology (EULAR) guidelines recommend RTKS.
The co-primary efficacy endpoints were the proportions of patients able to achieve remission at week 26 and those able to achieve sustained remission at week 52. Remission was defined as a Birmingham vasculitis activity score [BVAS] of 0 and no use of glucocorticoids for AAV 4 weeks before measurement.
Patients were given intravenous RTX 375 mg/m2 once a week for 4 weeks starting on the first day of the study. Repeat doses of RTX were not included, according to the approved labeled regimen at the start of the trial.
A total of 330 patients were included in the study, of which 214 (64.8%) were in the RTKS stratum. The average age of patients was 60 years, 76% of patients had renal vasculitis according to BVAS scores, 46% were positive for PR3-ANCA, and 58% had newly diagnosed AAV. More (57%) patients in the avacopan cohort were male compared with 48.6% in the prednisone group. Baseline eGFR in the avacopan and prednisone groups was 57,132.2 and 56,033.4 mL/min/1.73 m2, respectively.
After 26 weeks, 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 achieved in 71.0% (n = 76) of patients receiving avacopan and 56.1% (n = 60) of those treated with prednisone at week 52.
Serious adverse events (TEAEs) were observed in 34.6% (n = 37, 62 total events) of those in the avacopan group 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 in glucocorticoid-related toxicity and albuminuria were also observed in patients in the avacopan cohort.
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, IueH, SalvaraniC, et al. 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. 10-15. November 2023
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