article273

RITUXVAS

"Rituximab versus Cyclophosphamide in ANCA-Associated Vasculitis".The New England Journal of Medicine. 2010. 363:211-220.PubMed•Full text•PDF

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

Clinical Question

In patients with newly diagnosed ANCA-associated vasculitis and renal involvement, is rituximab-based regimen superior to standard intravenous cyclophosphamide for inducing sustained remission?

Bottom Line

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.

Major Points

Guidelines

As of August 2021, no guidelines reflecting the results of this trial have been described.

Design

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

Population

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

Interventions

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

Outcomes

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)

Secondary Outcomes
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)

Criticisms

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.

Funding

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.