Outcomes and compliance with standards of care in ANCA-associated vasculitis: insights from a large multi-region audit

Objectives: We aimed to conduct a large audit of routine care for patients with ANCA-associated vasculitis (AAV). Methods: We invited all 34 hospitals within one health region in England to undertake a retrospective case note audit of all patients newly-diagnosed or treated with Cyclophosphamide or Rituximab for AAV April 2013-December 2014. We compared clinical practice to the BSR guideline for the management of adults with AAV, and use of Rituximab to the NHS England commissioning policy and NICE Technology Appraisal. Results: We received data from 213 patients. Among 130 newly diagnosed patients, delay from admission to diagnosis ranged from 0-53 days (median 6, IQR 3-10.5) for those diagnosed as in-patients. BVAS score was recorded in 8% at diagnosis. Remission at 6 months was achieved in 83% of patients. 1-year survival was 91.5%. 130 patients received Cyclophosphamide for new-diagnosis or relapse. The correct dose of i.v. cyclophosphamide (within 100mg of the target dose calculated for age, weight and creatinine) was administered in 58%. 25% of patients had an infection requiring hospital admission during or within 6 months of completing their cyclophosphamide therapy. 76 patients received Rituximab for new-diagnosis or relapse. 97% patients met NHS England or NICE eligibility criteria. PJP prophylaxis (recommended in the summary of product characteristics) was given in only 65% of patients. Conclusion: We identified opportunities to improve care, including compliance with safety standards for delivery of cyclophosphamide. Development of a national treatment protocol / checklist to reduce this heterogeneity in care should be considered as a priority

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial.

Peer reviewed: TrueAcknowledgements: The RITAZAREM trial is directed by the European Vasculitis Society and the Vasculitis Clinical Research Consortium (VCRC). The primary sponsor is Cambridge University Hospitals NHS Foundation Trust, and there are collaboration and data-sharing agreements with the University of Pennsylvania and the University of Miyazaki and Okayama University in Japan.Funder: Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of JapanOBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier