Plasma Exchange Not Seen to Lessen Risk of Death or Kidney Failure in Severe ANCA Vasculitis Patients in Phase 3 Trial

Plasma Exchange Not Seen to Lessen Risk of Death or Kidney Failure in Severe ANCA Vasculitis Patients in Phase 3 Trial

Plasma exchange — a procedure that removes plasma from the blood and replaces it with a donor-derived substitute — does not lessen a risk of end-stage renal disease (ESRD) or death in patients with severe ANCA-associated vasculitis (AAV), data from a Phase 3 trial show.

Trial findings, however, appear to support using glucocorticoids at a lower-than-standard dose. Data showed no significant increase in the risk of ESRD or death, and fewer serious infections in those treated with a reduced steroid regimen.

The research, “The Effects of Plasma Exchange and Reduced-Dose Glucocorticoids during Remission-Induction for Treatment of Severe ANCA-Associated Vasculitis,” was presented by study co-author Peter A. Merkel, MD, at the recent 2018 American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP) Annual Meeting, held in Chicago.

Improvements to clinical outcomes in severe AAV when adding plasma exchange to standard treatment is uncertain. In particular, there is controversy as to whether plasma exchange – which helps remove AAV antibodies from circulation – helps lower ESRD and kidney damage, Merkel said during his presentation, according to a Healio Rheumatology news release written by Jason Laday.

Also unclear is if, compared to standard treatment with high-dose oral glucocorticoids – which significantly dampens the immune system – a lower-dose regimen lessens the risk of infection without raising the risk of ESRD or death.

Aiming to address these questions, researchers at the University of Pennsylvania, McMaster University in Canada, and University of Cambridge in the U.K conducted the PEXIVAS Phase 3 trial (NCT00987389), which enrolled 704 patients at 98 sites in 15 countries.

These patients (ages 15 and older) all had severe AAV, either new or relapsing disease. The majority (56%) were men and had AAV antibodies against MPO (59%), and 98% of them (691 people) patients had kidney disease (renal involvement). In total, 27% (191 patients) also had alveolar hemorrhage, which refers to bleeding in the lung’s tiny air sacs.

All patients were using immunosuppressive therapies — 15% received Rituxan (rituximab, by Genentech and Biogen) and 85% took cyclophosphamide.

Participants were randomly assigned to either seven plasma exchange procedures or no plasma exchange. They also received either a standard or a reduced-dose oral glucocorticoid regimen, which consisted of less than 60% of the standard regimen by six months. Patients were followed for up to seven years.

Death from any cause or ESRD — the trial’s primary outcome measures — was reported in 28% of patients who underwent plasma exchange and in 31% of those not receiving this procedure, a non-significant difference. As for steroids dose, death or ESRD occurred in 28% of patients taking the lower dose and in 26% of those receiving the standard regimen.

Data also showed that serious infections in the first year were less frequent in patients on the reduced glucocorticoids dose compared to the standard-dose group. Analyzing ESRDs or deaths separately led to similar results for both plasma exchange and glucocorticoid regimen comparisons.

“The primary results of PEXIVAS, regarding both the use of plasma exchange and dosing of glucocorticoids, will have immediate and substantial impact on the standard of care for patients with [AAV],” the scientists wrote.

“The impact of this trial is that it gives providers important information to think about regarding the use of plasma exchange — what its role may or may not be in our patients,” Merkel said. As for glucocorticoids, “I think it will almost certainly change the way we approach their use and the dosing for ANCA-associated vasculitis,” he added.

Merkel reports having received research funding from Biogen and Genentech/Roche.

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