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

OBJECTIVE: 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.

National recommendations for the management of children and young people with IgA vasculitis: a best available evidence, group agreement-based approach.

OBJECTIVE: IgA vasculitis (IgAV) is the most frequently experienced subtype of vasculitis seen in children. Most children fully recover, however, complications including chronic kidney disease are recognised. The aim of this project was to use a best available evidence, group agreement, based approach to develop national recommendations for the initial management of IgAV and its associated complications. METHODS: A fully representative multiprofessional guideline development group (GDG), consisting of 28 members, was formed and met monthly. Graded recommendations were generated using nationally accredited methods, which included a predefined scope, open consultation, systematic literature review, evidence appraisal, review of national or international guidelines and a period of open consultation. Audit measures and research priorities were incorporated. RESULTS: The IgAV GDG met over a 14-month period. A total of 82 papers were relevant for evidence synthesis. For the initial management, four topic areas were identified with five key questions generating six graded recommendations related to classification, specialist referral and musculoskeletal involvement. For the associated complications, five topic areas with 12 key questions generated 15 graded recommendations covering nephritis, gastrointestinal and testicular involvement, atypical disease and follow-up. Open consultation feedback was incorporated. The guidelines were endorsed by the UK Kidney Association and Royal College of Paediatrics and Child Health and are available online. CONCLUSION: Despite IgAV being a rare disease with limited evidence, a national standardised approach to the clinical management for children and young people has been achieved. This should unite approaches to care and act as a foundation for improvement.

High-fidelity simulation versus case-based tutorial sessions for teaching pharmacology: Convergent mixed methods research investigating undergraduate medical students' performance and perception.

INTRODUCTION: Medical educators strive to improve their curricula to enhance the student learning experience. The use of high-fidelity simulation within basic and clinical medical science subjects has been one of these initiatives. However, there is paucity of evidence on using simulation for teaching pharmacology, especially in the Middle East and North Africa region, and the effectiveness of this teaching modality, relative to more traditional ones, have not been sufficiently investigated. Accordingly, this study compares the effects of high-fidelity simulation, which is designed in alignment with adult and experiential learning theories, and traditional case-based tutorial sessions on the performance and perception of undergraduate Year 2 medical students in pharmacology in Dubai, United Arab Emirates. METHODS: This study employed a convergent mixed methods approach. Forty-nine medical students were randomly assigned to one of two groups during the 16-week pharmacology course. Each group underwent one session delivered via high-fidelity simulation and another via a case-based tutorial. A short multiple-choice question quiz was administered twice (immediately upon completion of the respective sessions and 5 weeks afterwards) to assess knowledge retention. Furthermore, to explore the students' perceptions regarding the two modes of learning delivery (independently and in relation to each other), an evaluation survey was administered following the delivery of each session. Thereafter, the iterative joint display analysis was used to develop a holistic understanding of the effect of high-fidelity simulation in comparison to traditional case-based tutorial sessions on pharmacology learning in the context of the study. RESULTS: There was no statistically significant difference in students' knowledge retention between high-fidelity simulation and case-based tutorial sessions. Yet, students expressed a greater preference for high-fidelity simulation, describing the corresponding sessions as more varied, better at reinforcing learning, and closer to reality. As such, the meta-inferences led to expansion of the overall understanding around students' satisfaction, to both confirmation and expansion of the systemic viewpoint around students' preferences, and lastly to refinement in relation to the perspective around retained knowledge. CONCLUSION: High-fidelity simulation was found to be as effective as case-based tutorial sessions in terms of students' retention of knowledge. Nonetheless, students demonstrated a greater preference for high-fidelity simulation. The study advocates caution in adapting high-fidelity simulation, where careful appraisal can lend itself to identifying contexts where it is most effective.

Outcomes and compliance with standards of care in anti-neutrophil cytoplasmic antibody-associated vasculitis-insights from a large multiregion audit.

OBJECTIVES: We aimed to conduct a large audit of routine care for patients with ANCA-associated vasculitis. 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 CYC or rituximab (RTX) for ANCA-associated vasculitis from April 2013 to December 2014. We compared clinical practice to the British Society for Rheumatology guidelines for the management of adults with ANCA-associated vasculitis and the use of RTX with the National Health Service (NHS) England commissioning policy and National Institute for Health and Care Excellence (NICE) technology appraisal. RESULTS: We received data from 213 patients. Among 130 newly diagnosed patients, delay from admission to diagnosis ranged from 0 to 53 days (median 6, interquartile range 3-10.5) for those diagnosed as inpatients. BVAS was recorded in 8% of patients at diagnosis. Remission at 6 months was achieved in 83% of patients. The 1-year survival was 91.5%. A total of 130 patients received CYC for new diagnosis or relapse. The correct dose of i.v. CYC (within 100 mg of the target dose calculated for age, weight and creatinine) was administered in 58% of patients. A total of 25% of patients had an infection requiring hospital admission during or within 6 months of completing their CYC therapy. Seventy-six patients received RTX for new diagnosis or relapse. A total of 97% of patients met the NHS England or NICE eligibility criteria. Pneumocystis jiroveci pneumonia 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 CYC. Development of a national treatment protocol/checklist to reduce this heterogeneity in care should be considered as a priority.