Case study: PEXIVAS
Plasma Exchange and Glucocorticoid Dosing in the treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis
• The largest trial in Antibody Associated Vasculitis (AAV) undertaken to date
• Study ran June 2010 – September 2016
• An international multi-centre, randomised control trial across 110 centres from Europe, North America, Australia, New Zealand and Japan
• PEXIVAS was funded by the NIHR Health Technology Assessment (HTA) Programme and several international funders.
• Study recruitment was supported by the NIHR Clinical Research Network
• The NIHR recruited 178 participants in good time and exceeded its recruitment target across 19 sites in the UK
• UK Chief Investigator: Professor David Jayne, Cambridge University Hospitals NHS Foundation Trust
Severe, anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV) is a rare disease of the immune system diagnosed in around 14-30 per 100,000 people in UK each year. There are two major problems that hinder the treatment of ANCA associated vasculitis. The first is a lack of treatment to bring the disease under control quickly before it causes major organ damage. The second is a high degree of treatment related toxicity.
PEXIVAS looked to examine these issues in patients with severe ANCA associated vasculitis and answer two key questions. Does plasma exchange prolong the time before kidney failure or death in severe ANCA associated vasculitis? Is a reduced oral glucocorticoid treatment (a class of steroid hormone) equivalent to the standard treatment but safer? The ultimate aim is to improve patient survival and reduce the frequency of kidney failure in patients with ANCA associated vasculitis.
“PEXIVAS has shown how an international collaboration, with funding from multiple government agencies, can successfully conduct a large rare disease study. The results will be of direct benefit to patients with vasculitis and will reduce healthcare costs.”
Professor David Jayne, Director of the Vasculitis and Lupus Service, Addenbrooke’s Hospital and Professor of Clinical Autoimmunity, University of Cambridge
“Ultimately, patients will no longer endure the hassle of a treatment that offers no benefit and will be less likely to experience severe infection following treatment. PEXIVAS has shown how treatment for ANCA associated vasculitis can be made safer and save the NHS money.”
Professor David Wheeler, NIHR National Specialty Lead for Renal Disorders
Inflammation is your immune system’s natural response to injury or infection but in vasculitis the immune system attacks healthy blood vessels. Typically, with AAV small blood vessels are destroyed as they become swollen and narrow. AAV can affect several organs including the kidney, stomach, intestine and lungs. ANCA associated vasculitis carries a poor prognosis with up to 50 per cent of patients dying or developing kidney failure within five years. Plasma is a part of blood.
Where a disease causes harmful substances to circulate in the blood, plasma exchange is a process that allows these harmful substances to be removed. Plasma exchange involves removing plasma from the blood and replacing it with new plasma fluid. 704 patients with ANCA associated vasculitis were randomly assigned to receive plasma exchange or to not receive plasma exchange. Patients were also randomly assigned to receive either a standard dose of steroids or a low-dosage which was predicted to be safer and reduce treatment related toxicity.
Outcomes and findings
The study found that plasma exchange did not significantly prolong the time to kidney failure or death. PEXIVAS also established that reduced glucocorticoid treatment was equivalent to standard treatment but safer. It was also associated with a reduction in severe infections. Further studies are being planned to examine the impact of a low dose glucocorticoid treatment.
Value to the NHS
The study findings will lead to cost savings in the NHS. Plasma exchange will no longer be routinely given for severe ANCA associated vasculitis, meaning patients will no longer undergo the inconvenience of unnecessary and costly treatment. Moreover, with fewer severe infections associated with a lower dose glucocorticoid treatment, there will be less demand on financial resources to manage such complications. Patient outcomes will be improved by the development of a safer glucocorticoid treatment.
• PEXIVAS: protocol for a randomized controlled trial https://trialsjournal.biomedcentral.com/ articles/10.1186/1745-6215-14-73
• University of Birmingham https://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/ renal/PEXIVAS/index.aspx