By Gene Emery
(Reuters Health) - In findings that raise questions about the go-to treatment for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, researchers behind the PEXIVAS study have concluded that plasma exchange does not reduce the odds of death or end-stage kidney disease.
They also found that a reduced-dose regimen of glucocorticoids during the first six months of treatment was not inferior to the standard dose in terms of disease progression, while sharply lowering the odds of serious infection.
"I think this is going to make people think twice about who to prescribe plasma exchange for," chief author Dr. Michael Walsh of the Population Health Research Institute at McMaster University in Hamilton, Ontario, told Reuters in a telephone interview.
That treatment is an attempt to remove the antibodies believed to be the root cause of the vasculitis. Based on the new findings, published in The New England Journal of Medicine, it's not clear that any subset of patients would benefit from the therapy.
As for prednisone therapy, "we found by reducing the dose by about 45%, we could reduce infections by about 30%, and infection is the number one cause of death from this disease," said Dr. Walsh, who is also a nephrologist at St. Joseph's Healthcare Hamilton.
That second finding, involving a treatment that has been a mainstay for decades, is going to raise questions about whether reducing the dose further or using a different regimen will work even better.
For example, short initial bursts may be a more powerful weapon against the condition, which is invariably fatal if not treated, with 90% of the deaths coming within the first year. "There's going to be a question of how far we can cut back," said Dr. Walsh.
The open-label study included 704 volunteers with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. All of the patients had already developed kidney problems. The disease can also cause serious bleeding in the lungs.
ANCA vasculitis affects about 1 in 2,380 people in the United States, causing blood vessels to swell as the body's own immune cells attack them.
The study, the largest clinical trial for ANCA-associated vasculitis, was conducted at 95 centers in 16 countries. All of the volunteers had either diffuse pulmonary hemorrhage or an estimated glomerular filtration rate of less than 50 ml/min/1.73 m2. They were followed for up to 7 years; the median duration was 2.9 years.
Among the half who received 7 plasma exchanges over 14 days to try to rapidly remove the ANCAs, the combined rate of end-stage kidney disease or death from any cause was 28.4% with plasma exchange and 31.0% without (P=0.27). The volunteers were aware of their treatment group.
Plasma exchange should no longer be standard therapy for these types of patients, said Drs. Vimal Derebail and Ronald Falk of the University of North Carolina at Chapel Hill School of Medicine in a Journal editorial.
At the same time, half the group randomly received a reduced dose of oral glucocorticoids, amounting to about half the standard dose, with the reduction coming at the start of the second week of therapy. The rest received a standard dose that was tapered more gradually.
The composite endpoint was reached by 27.9% in the reduced-dose group versus 25.5% in the standard-dose contingent, another non-significant difference for inferiority.
Serious infections were 31% less common in the low-dose group, with 142 such cases in the reduced-dose group versus 180 among the standard-dose patients.
Yet while the incidence of end-stage kidney disease didn't differ significantly between the groups based on their steroid dose, there were 84% more serious adverse kidney-related events with the reduced-dose regimen.
In their editorial, Drs. Derebail and Falk noted that patients did not have baseline kidney biopsy data and without it, "the proportion of patients who had kidney dysfunction caused by active inflammation, which may respond to immunomodulatory therapy, as compared with chronic sclerosis, which would not respond to this therapy, is unknown. A subgroup of patients with aggressive kidney disease with minimal scarring may benefit from plasma exchange."
"Aside from this caveat, the results of the PEXIVAS trial show that plasma exchange should not be included in standard induction therapy for patients with ANCA-associated vasculitis who have kidney dysfunction," they said.
However, they added, "In our judgment, until a study specifically designed to evaluate efficacy in patients with pulmonary hemorrhage has been performed, plasma exchange should remain part of the induction regimen for patients with ANCA-induced pulmonary hemorrhage."
SOURCE: https://bit.ly/2uwaCjl The New England Journal of Medicine, online February 12, 2020