Discontinuation of rituximab compared with rituximab maintenance in ANCA-associated vasculitis – a randomized non-blinded controlled trial (DISRITUX)

Prior treatment

• Participant in another clinical trial with therapeutic intervention or use of any other investigational agent
• Previous therapy with any of the following: - any biological B cell depleting agent other than rituximab during the last 6 months (i.e Obinutuzumab, Belimumab) - 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)
• Recurrent AAV relapses less than 6 months off immunosuppressive medication

Other illness

• History of malignancy within the past five years or any evidence of persistent malignancy. 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 is allowed
• 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
• Ongoing therapy with any of the following. - disease modifying therapy related for AAV such as methotrexate, azathioprine, and mycophenolate mofetil or glucocorticoid >5 mg daily
• Significant or uncontrolled medical disease not related to AAV, which in the investigator’s opinion would preclude patient participation
• Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis
• History of severe allergic or anaphylactic reactions to humanized or murine chimeric monoclonal antibodies
• Past or current history of hepatitis B virus, current active hepatitis C

Lab values

• Significantly abnormal eGFR at screening (≤15 eGFR ml/min/1.73m2)
• Hypogammaglobulinemia, IgG <3 g/L
• Females who are lactating or pregnant at screening (verified with a negative urine or serum pregnancy test at screening visit).
• Bone marrow suppression as evidenced by a total white count < 3.0 x109/l and/or neutropenia neutrophil count < 1.5 × 109

• Informed consent given by patient according to national regulations
• AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference
• Current or history of PR3/MPO-ANCA positivity by ELISA
• A stable remission (BVAS =0) for the last 24 months
• Has received a minimum of 24 months of RTX maintenance therapy and last dose minimum 6 months prior to screening. A Rituximab dose of 500 mg or 1000 mg 6 months before inclusion will be accepted
• Females of childbearing potential must agree to avoid pregnancy during treatment with RTX during 12 months after discontinuation of RTX. They also must have a negative urine or serum pregnancy test at the screening visit. Adequate contraception methods must be followed according to clinical routine for these patients