Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial.

Autor:	Zonozi R; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA rzonozi@yahoo.com.; Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Cortazar FB; New York Nephrology Vasculitis and Glomerular Center, Albany, New York, USA., Jeyabalan A; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA.; Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Sauvage G; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Nithagon P; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Huizenga NR; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Rosenthal JM; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Sipilief A; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Cosgrove K; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Laliberte KA; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Rhee EP; Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Pendergraft WF 3rd; Genentech Inc, South San Francisco, California, USA., Niles JL; Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, Massachusetts, USA.; Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Feb 15; Vol. 83 (3), pp. 351-359. Date of Electronic Publication: 2024 Feb 15.
DOI:	10.1136/ard-2023-224489
Abstrakt:	Objective: To compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis. Methods: We conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing at least 2 years of fixed-schedule rituximab. In the B cell arm, rituximab was reinfused upon B cell repopulation; in the ANCA arm, rituximab was reinfused upon significant rise in ANCA level. Evaluations were conducted every 3 months. The primary endpoint was clinical relapse, defined as a modified BVAS/WG >0 by 36 months. Secondary endpoints included serious adverse events (SAEs) and rituximab exposure. Results: 115 patients were enrolled. Median follow-up time was 4.1 years (IQR 2.5-5.0). By Kaplan-Meier analysis, 4.1% (95% CI 1.0 to 15.6) of patients had a clinical relapse in the B cell arm, compared with 20.5% (95% CI 11.9 to 34.1) in the ANCA arm, at 3 years after study entry (log-rank p=0.045). Total SAEs, including infectious SAEs, and deaths did not differ. The number of SAEs due to COVID-19 was higher in the B cell arm (p=0.049). In the B cell arm, patients received a mean of 3.6 (SD 2.4) infusions (3.6 g) per person over the median study follow-up time of 4.1 years, compared with 0.5 (SD 1.4) infusions (0.5 g) per patient in the ANCA arm (p<0.001). Conclusions: Rituximab dosed for B cell repopulation results in fewer clinical relapses than when dosed for a rise in ANCA level in maintenance of remission for ANCA vasculitis. Overall safety was equivalent; SAEs due to COVID-19 and rituximab exposure were higher with the B cell strategy. Trial Registration Number: NCT02749292. Competing Interests: Competing interests: FBC has served as a consultant for Amgen, Valenza Bio, Travere Therapeutics and Aurinia Pharmaceuticals. FBC has received speaking fees from Amgen, Aurinia Pharmaceuticals and Calliditas Therapeutics. WFPIII has served as a consultant for GSK. WFPIII has received speaker fees from GSK and Chemocentryx. WFPIII’s employment with Genentech began after study completion. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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