Despite the publication of previous clinical trials that showed plasma exchange could possibly be a viable treatment for patients with severe ANCA-associated vasculitis, a new study recently published in the New England Journal of Medicine shows that the treatment, in combination with standard therapy, didn't improve outcomes for patients or lower fatality rates or slow the progression to end-stage kidney disease.
"Previous trials have suggested a substantial benefit of plasma exchange in patients with severe kidney disease with respect to reducing the need for dialysis at 12 months. In contrast, our trial did not show large effects," wrote the authors who were led by Michael Walsh, M.D., Ph.D., McMaster University–Hamilton Health Sciences, Ontario. "This difference among the findings highlights the possibility of chance findings in small trials and the importance of larger trials with longer follow-up."
Some international guidelines currently recommend use plasma exchange to treat ANCA-associated vasculitis with pulmonary hemorrhage, but these guidelines, the authors wrote, are based on small observational studies, not the larger clinical trials he suggests are needed to support formal treatment recommendations.
In this study, researchers also examined the use of oral glucocorticoids finding that a reduced dose was just as effective the standard recommended dose in decreasing the risk of serious infections without increasing the risk of adverse events.
This clinical trial, which was called PEXIVAS, trial included 704 patients with severe ANCA-associated vasculitis who were randomly assigned to undergo seven plasma exchanges within the first 14 days or no plasma exchange (control group), and to follow either a standard-dose or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to seven years.
The primary outcome was a composite of death from any cause or end-stage kidney disease of 12 or more continuous weeks of hemodialysis or peritoneal dialysis or kidney transplant. The secondary outcomes were death from any cause, end-stage kidney disease, sustained remission, serious adverse events, serious infections within one year, and health-related quality of life.
The primary outcome of death from any cause or end-stage kidney disease occurred in 28.4 percent of the plasma-exchange group and in 31 percent of the control group. For the glucocorticoid regimes, death from any cause or end-stage kidney disease occurred in 27.9 percent of the reduced-dose group and in 25.5 percent of the standard-dose group, indicating noninferiority. Serious infections at one year were less common with use of reduced-dose glucocorticoids than with use of standard-dose glucocorticoids (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93).
“The effect of plasma exchange added to immunosuppressive therapy as compared with immunosuppressive therapy alone on clinically important outcomes, such as death and ESKD, is
uncertain,” the authors wrote. “High-quality data are lacking regarding an effective and relatively safe rate at which glucocorticoid doses can be tapered in patients with ANCA-associated vasculitis.”
In an accompanying editorial, Vimal Derebail, M.D., M.P.H., and Ronald Falk, M.D., of the University of North Carolina, wrote, “The findings indicate that plasma exchange should not be used in most patients with ANCA-associated vasculitis who have severe kidney dysfunction,” but “may benefit carefully selected subgroups of patients, including patients with concomitant anti–glomerular basement membrane disease and perhaps those with rapidly progressive glomerulonephritis but minimal scarring.
They added that plasma exchange should remain part of the induction regimen for patients with ANCA-induced pulmonary hemorrhage, until further research is completed in these patients.
Michael Walsh, Peter A. Merkel, Chen-Au Peh, et al. “Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis.” New England Journal of Medicine. February 13, 2020. DOI: 10.1056/NEJMoa1803537
Vimal Derebail, Ronald Falk. “ANCA-Associated Vasculitis — Refining Therapy with Plasma Exchange and Glucocorticoids.” New England Journal of Medicine. February 13, 2020. DOI: 10.1056/NEJMe1917490