title: Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial.
abstract: Rituximab is effective as therapy for induction of remission in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the effect of rituximab is not sustained, and subsequent relapse rates are high, especially in patients with a history of relapse. There is a need to identify whether maintenance therapy with rituximab is superior to the current standard of azathioprine or methotrexate for prevention of relapse following induction with rituximab.
  
  
  
  RITAZAREM is an international, multicenter, open-label, randomized controlled trial designed to demonstrate the superiority of repeated doses of intravenous rituximab compared to daily orally administered azathioprine as a relapse prevention strategy in patients with AAV with relapsing disease who undergo induction of remission with rituximab. Patients with AAV will be recruited at the time of relapse and will receive rituximab and glucocorticoid induction therapy. If the disease is controlled by 4 months, patients will be randomized in a 1:1 ratio to receive rituximab (1000 mg every 4 months for five doses) or azathioprine (2 mg/kg/day) as maintenance therapy. Patients will be followed for a minimum of 36 months. The primary outcome is the time to disease relapse. It is estimated that 190 patients will need to be recruited to ensure that at least 160 are randomized.
  
  
  
  The RITAZAREM trial will provide the largest trial dataset for the use of rituximab as remission-induction therapy for patients with AAV comparing two remission-maintenance strategies following induction with rituximab, and explore whether prolonged B-cell depletion leads to sustained treatment-free remissions after discontinuation of immunosuppressive therapy.
  
  
  
  ClinicalTrials.gov identifier: NCT01697267 . Registered on 31 August 2012.
authors.affiliation: University of Cambridge Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Seerapani
authors.initials: S
authors.lastname: Gopaluni
authors.affiliation: University of Cambridge Hospitals NHS Foundation Trust, Cambridge, UK. Ronasmith@doctors.net.uk.|Addenbrooke's Hospital, Box 118, Hills Road, Cambridge, CB2 0QQ, UK. Ronasmith@doctors.net.uk.
authors.forename: Rona M
authors.initials: RM
authors.lastname: Smith
authors.affiliation: University of Cambridge Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lewin
authors.affiliation: Division of Rheumatology and Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: McAlear
authors.affiliation: University of Cambridge Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Mynard
authors.affiliation: University of Cambridge Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Jones
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.affiliation: Division of Rheumatology and Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.affiliation: University of Cambridge Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: David R W
authors.initials: DR
authors.lastname: Jayne
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001315:Australia; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D005060:Europe; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D060046:Maintenance Chemotherapy; D009520:New Zealand; D012008:Recurrence; D012074:Remission Induction; D012107:Research Design; D000069283:Rituximab / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000069283:Rituximab; D001379:Azathioprine
keywords: ANCA-associated vasculitis; Azathioprine; RITAZAREM; Randomized clinical trial; Rituximab