- At least 15 years old.
- At least 40 kg in weight.
- Diagnosis of either GPA or MPA1.
- Active disease, minimum BVAS/WG2.
- Severe disease, with one or more BVAS/WG items, requiring CYC3 for usual standard of care.
- ANCA4 positive (either PR3- or MPO-ANCA).
- Willing to practice contraception and refrain from breastfeeding.
- Willing to comply with study procedures.
- Competence and willingness to provide informed consent.
- Limited disease (not treated with CYC under standard of care).
- On mechanical ventilation at time of eligibility.
- History of severe allergic reactions to human or chimeric monoclonal antibodies or murine protein, or history of human antichimeric antibodies (HACA).
- Active systemic infection.
- Deep space infection within 6 months.
- Known active hepatitis B or C or documented history of hepatitis B, C, or HIV.
- Significant acute or chronic liver disease
- Antiglomerular basement membrane disease.
- Active or history of malignancy in the last 5 years5.
- Drug or alcohol abuse.
- Cytopenias: white blood cell count < 4,000/mm3, platelet count < 120,000/mm3.
- Liver function tests: Serum AST6 or ALT concentration greater than 2.5 times the upper limit of normal that is not related to AAV.
- Creatinine: Serum creatinine > 4.0 mg/dL that is attributed to renal failure from a current flare.
- Specific immunosuppressive or biologic agents (Proscribed Medications).
- Glucocorticoids for Longer than 14 days prior to enrollment unless they were on a stable maintenance dose of prednisone at the time of the flare.
- Daily oral CYC for more than 7 days prior to enrollment.
- Completed a remission induction course of oral or intravenous CYC within 4 months of enrollment
- Previous therapy with rituximab
- Previous therapy with alemtuzumab
- Anti-TNF therapy within 5 half-lifes of the specific agent
- Plasma exchange within 3 month of enrollment
- Vaccines: They have had a live vaccine fewer than four weeks before randomization.