Exploring Durable Remission With Rituximab in Antineutrophil Cytoplasmic Antibody(ANCA)-Associated Vasculitis

Inclusion Criteria: Subjects enrolled in the study must meet the following inclusion criteria:

1. Clinical diagnosis of granulomatosis with polyangiitis (GPA) or microscopicPolyangiitis (MPA), consistent with Chapel-Hill Consensus Conference definitions26
2. Aged at least 18 years, with newly-diagnosed or relapsed AAV with 'generaliseddisease', defined as involvement of at least one major organ (e.g. kidney, lung,heart, peripheral or central nervous system), requiring induction treatment withcyclophosphamide or rituximab
3. Positive test for anti-PR3 or anti-MPO (current or historic)
4. Willing and able to give written Informed Consent and to comply with the requirementsof the study protocol

Exclusion criteria: Subjects will be excluded from participation if they meet any of the following exclusioncriteria:

1. Pregnant or breast-feeding
2. Active pregnancy, as proven by a positive urine beta-HCG test or a positive serumbeta-HCG
3. Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA < 0.1 g/L)
4. Active infection not compatible with start of remission-induction therapy in theopinion of the treating physician and/or investigator, e.g.:

• Serological evidence of viral hepatitis defined as: patients positive for HbsAgtest or HBcAb or a positive hepatitis C antibody not treated with antiviralmedication
• Have a historically positive HIV test or test positive at screening for HIV

5. Have a history of a primary immunodeficiency
6. Have a significant infection history that in the opinion of the investigator wouldmake the candidate unsuitable for the study
7. Have a neutrophil count of < 1.5x10E9/L
8. Evidence of hepatic disease: AST, ALT, alkaline phosphatase, or bilirubin > 3 timesthe upper limit of normal before start of dosing
9. Have any other clinically significant abnormal laboratory value in the opinion of theinvestigator
10. Required dialysis or plasma exchange within 12 weeks prior to screening
11. Received intravenous glucocorticoids, >3000mg methylprednisolone equivalent, within 4weeks prior to screening
12. Immunization with a live vaccine 1 month before screening
13. History or presence of any medical condition or disease which, in the opinion of theInvestigator, may place the patient at unacceptable risk for study participation.
14. Have a history of an anaphylactic reaction to parenteral administration of contrastagents, human or murine proteins or monoclonal antibodies