Intervention: Azathioprine
Trial phase: Phase 3
ATC code: L04AX01
SMILES: Cn1cnc([N+](=O)[O-])c1Sc1ncnc2nc[nH]c12
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 85
Group description: Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27.

Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27.

The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily.

If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Eligibility criteria:
Inclusion Criteria:

A diagnosis of AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference
Current or historical PR3/MPO ANCA positivity by ELISA
Disease relapse defined by one major or three minor disease activity items on the Birmingham Vasculitis Activity Score for Wegeners (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)
Written informed consent

Exclusion Criteria:

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

Exclusions related to medication:

Previous therapy with:

Any biological B cell depleting agent (such as rituximab or belimumab) within the past 6 months
Alemtuzumab or anti-thymocyte globulin (ATG) within the last 12 months
IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months
Any investigational agent within 28 days of screening, or 5 half lives of the investigational drug (whichever is longer)

Exclusions related to general health:

Significant or uncontrolled medical disease not related to AAV, which in the investigators opinion would preclude patient participation
Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis,
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).
History of severe allergic or anaphylactic reactions to humanised or murine chimeric monoclonal antibodies
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.
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.
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.
Pregnancy or inadequate contraception in pre-menopausal women
Breast feeding or lactating

Exclusion criteria related to laboratory parameters:

Bone marrow suppression as evidenced by a total white count < 4 x109/l, haemoglobin < 7 gm/dl or platelet count < 100,000/μl
Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the upper limit of normal, unless attributed to vasculitis