The RAVE Trial studied Rituxan compared with cyclophosphamide (CYC) followed by azathioprine (AZA) for the induction of remission in Granulomatosis with Polyangiitis and Microscopic Polyangiitis1
A multicenter, randomized, double-blind, double-dummy, noninferiority trial1
- Compared Rituxan (rituximab) to cyclophosphamide (CYC) followed by azathioprine (AZA) for complete remission induction.1
Primary end point: Complete Remission was defined as no disease activity (defined as BVAS/GPA of 0)* and successful tapering off of prednisone by Month 6.1
- The RAVE Trial included patients with1:
- Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA)
- Newly diagnosed or relapsing disease
- MPO or PR3 ANCA-positivity at baseline
Treatment arms were randomized with the objective of similar baseline demographic and disease characteristics. Notable baseline information includes1:
- Mean age of patients at onset of symptoms1
- Rituxan group 54.0 years (ranged from 16 to 92)
- CYC group 51.5 years (ranged from 15 to 80)
- Mean creatinine clearance at baseline2
- Rituxan arm 76.51 mL/min
- CYC followed by AZA arm 91.40 mL/min
- A total of 197 patients completed the study1
- 99 patients received Rituxan plus glucocorticoid and CYC placebo
- 98 patients received CYC plus glucocorticoid and Rituxan placebo followed by AZA maintenance regimen at remission
The RAVE Trial was conducted by the Immune Tolerance Network and sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Genentech and Biogen Idec also provided funding and study drug.1
- The randomization was stratified by clinical study center and type of ANCA (PR3 or MPO). Patients were assigned 1:1 and balanced according to disease type, newly diagnosed or relapsing disease, disease activity, organ involvement, pre-enrollment therapy, past exposure to cyclophosphamide, and total glucocorticoids administered in the interval from 14 days before informed consent was obtained to first investigational infusion.
- The BVAS/GPA (Birmingham Vasculitis Activity Score for Granulomatosis with Polyangiitis) is a validated tool that quantifies disease activity based on evidence of active disease in 8 organ systems, an "other" category, and a physician's global assessment. Disease features are scored only if they are attributed to active vasculitis, as opposed to damage. Adapted from Stone et al.3
- BVAS/GPA≥3, severe disease.
- BVAS/GPA=0, patients reaching clinical remission with no disease activity.
- Stone JH, Merkel PA, Spiera R, et al; for the RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232.
- Data on file, Genentech USA/Biogen Idec.
- Stone JH, Hoffman GS, Merkel PA, et al; for the International Network for the Study of the Systemic Vasculitides (INSSYS). A disease-specific activity index for Granulomatosis with Polyangiitis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum. 2001;44(4):912-920.
Rituxan (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA).
Rituxan is not recommended for treatment of patients with severe active infections.
IMPORTANT SAFETY INFORMATION
Rituxan administration can result in serious, including fatal, adverse reactions. These include:
- infusion reactions
- tumor lysis syndrome (TLS)
- severe mucocutaneous reactions
- progressive multifocal leukoencephalopathy (PML)
Warnings and Precautions
Rituxan administration can also result in additional serious, including fatal, adverse reactions including:
- hepatitis B reactivation
- other infections including bacterial, fungal, new or reactivated viral infections
- cardiovascular events
Use of concomitant immunosuppressants other than corticosteroids has not been studied in GPA or MPA patients exhibiting peripheral B-cell depletion following treatment with Rituxan.
Observe patients closely for signs of infection if immunosuppressants other than corticosteroids are used concomitantly.
Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia and peripheral edema.