"Rituximab versus Cyclophosphamide in ANCA-Associated Vasculitis".The New England Journal of Medicine. 2010. 363:211-220.
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Contents 1Clinical Question 2Bottom Line 3Major Points 4Guidelines 5Design 6Population 6.1Inclusion Criteria 6.2Exclusion Criteria 6.3Baseline Characteristics 7Interventions 8Outcomes 8.1Primary Outcomes 8.2Secondary Outcomes 9Criticisms 10Funding 11Further Reading
In patients with newly diagnosed ANCA-associated vasculitis and renal involvement, is rituximab-based regimen superior to standard intravenous cyclophosphamide for inducing sustained remission?
A rituximab-based regimen was not found to be superior to standard intravenous cyclophosphamide treatment in inducing sustained remission for ANCA-associated vasculitis, maintaining high remission rates in both groups without reducing early severe adverse events.
The RITUXVAS trial did not demonstrate the superiority of rituximab over cyclophosphamide in inducing sustained remission in patients with ANCA-associated vasculitis, with both regimens showing similarly high remission rates. Treatment with rituximab also did not lead to a reduction in early severe adverse events, although it allows for reduced exposure to cyclophosphamide and avoidance of maintenance immunosuppression.
As of August 2021, no guidelines reflecting the results of this trial have been described.
Open-label, parallel-group, randomized trial N=44 patients with newly diagnosed ANCA-associated vasculitis and renal involvement Rituximab group (n=33) Control group (standard intravenous cyclophosphamide followed by azathioprine) (n=11) Setting: 8 centers in Europe and Australia Enrollment: June 2006 to June 2007 Mean follow-up: 12 months Primary endpoints: Sustained remission rates at 12 months, severe adverse events
Inclusion Criteria New diagnosis of ANCA-associated vasculitis ANCA positivity Renal involvement with necrotizing glomerulonephritis on biopsy or red-cell casts/hematuria on urinalysis
Exclusion Criteria Not described
Baseline Characteristics Median age: 68 years Glomerular filtration rate (GFR): 18 ml per minute per 1.73 m² Use of plasma exchange balanced between groups
Rituximab group: Intravenous rituximab at 375 mg/m² for 4 weeks with two intravenous cyclophosphamide pulses, without azathioprine Control group: Intravenous cyclophosphamide for 3-6 months followed by azathioprine Both groups received standard glucocorticoid regimen
Primary Outcomes Sustained remission Rituximab group: 76% Control group: 82% (P=0.68) Severe adverse events Rituximab group: 42% Control group: 36% (P=0.77)
Time to remission: Similar between groups Change in GFR: Median increase, rituximab group = 19 ml/min; control group = 15 ml/min (P=0.14) Prednisolone dose: Similar reduction in both groups Quality of life (SF-36): Improvement in both groups, but rituximab group showed a significant improvement in the mental component (P=0.04), with two outliers influencing results Vasculitis Damage Index: Changes similar between groups Relapse: 15% in rituximab group, 10% in control group (P=0.70)
The trial did not determine long-term efficacy and safety beyond 12 months, and long-term benefits of rituximab remain uncertain. The trial's relatively small sample size and open-label design could potentially introduce bias.
Supported by Cambridge University Hospitals National Health Service Foundation Trust, F. Hoffmann–La Roche with provision of rituximab, and a research grant contributing to trial costs.
Original publication in The New England Journal of Medicine (2010): [PubMed•Full text•PDF]