RITAZAREM

To be included in the trial the patient must have:

1. Provided written informed consent (15 years and above)

2. A diagnosis of AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference

3. Current or historical PR3/MPO ANCA positivity by ELISA

4. Disease relapse defined by one major or three minor disease activity items on the Birmingham Vasculitis Activity Score for Wegener’s (BVAS/WG), in patients that have previously achieved remission following at least 3 months of induction therapy, with a combination of glucocorticoids and an immunosuppressive agent (cyclophosphamide or methotrexate or rituximab or mycophenolate mofetil)

All patients will receive induction therapy with rituximab. Only those entering remission by 4 months will be randomised 1:1 to the rituximab or control groups

1. Age < 15 years (age < 18 years at centres that do not treat paediatric patients)

2. Exclusions related to medication:

   Previous therapy with:

   1. Any biological B cell depleting agent (such as rituximab or belimumab) within the past 6 months

   2. Alemtuzumab or anti-thymocyte globulin (ATG) within the last 12 months

   3. IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months

   4. Any investigational agent within 28 days of screening, or 5 half lives of the investigational drug (whichever is longer)

3. Exclusions related to general health:

   1. Significant or uncontrolled medical disease not related to AAV, which in the investigators opinion would preclude patient participation

   2. Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis,

   3. Any concomitant condition anticipated to likely require greater than 4 weeks per year of oral or systemic glucocorticoid use and which would preclude compliance with the glucocorticoid protocol (e.g. poorly-controlled asthma, COPD, psoriasis, or inflammatory bowel disease).

   4. History of severe allergic or anaphylactic reactions to humanised or murine chimeric monoclonal antibodies

   5. Known infection with HIV (HIV testing will not be a requirement for trial entry); a past or current history of hepatitis B virus or hepatitis C virus infection.

   6. Ongoing or recent (last 12 months) evidence of active tuberculosis or known active infection (screening for tuberculosis is part of "standard of care‟ in patients with established AAV) or evidence of untreated latent tuberculosis. Screening for tuberculosis is as per local practice.

   7. History of malignancy within the past five years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure.

   8. Pregnancy or inadequate contraception in pre-menopausal women

   9. Breast feeding or lactating

   10. Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.

4. Exclusion criteria related to laboratory parameters:

   1. Bone marrow suppression as evidenced by a total white count < 4 x109/l, haemoglobin < 7 gm/dl or platelet count < 100,000/μl

   2. Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the upper limit of normal, unless attributed to vasculitis