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Abstract
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.
- Rituximab
- Systemic vasculitis
- Autoantibodies
- B-Lymphocytes
Data availability statement
Deidentified data are available on reasonable request to the corresponding author and after appropriate ethical approvals.
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Data availability statement
Deidentified data are available on reasonable request to the corresponding author and after appropriate ethical approvals.
Footnotes
Handling editor Josef S Smolen
Contributors JLN, WFPIII, FBC, and KAL were involved in study conception. All authors were involved in data acquisition and interpretation. RZ did the study analysis and wrote the manuscript with support from JLN. All authors contributed critical appraisal to the final manuscript. RZ is the guarantor for the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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