Plasma Exchange Not Associated With Reduced Incidence of End-Stage Kidney Disease or Death in ANCA Vasculitis

Illustration of vasculitis, an inflammation of the blood vessels that may cause thickening, weakening, narrowing, and scarring of the blood vessel walls. This condition occurs if the immune system attacks the blood vessels. This may happen as a result of an infection, medicine, or another disease or condition. The blood vessel shown middle right is being attacked by macrophages and killer cells that are part of the body`s immune system.
Researchers compared the efficacy of plasma exchange vs no plasma exchange, in terms of end-stage kidney disease or death, in patients with severe ANCA-associated vasculitis.

Plasma exchange does not reduce the incidence of either death or end-stage kidney disease (ESKD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, according to study results published in the New England Journal of Medicine.

Researchers conducted a randomized, controlled trial with a 2-by-2 factorial design (PEXIVAS; Identifier: NCT00987389) to assess the efficacy of plasma exchange in patients with ANCA-associated vasculitis in regard to either death or ESKD. Investigators also compared a reduced-dose regimen with a standard-dose regimen of glucocorticoids over the first 6 months of the treatment period to determine noninferiority.

In total, the trial included 704 patients at 95 centers across 16 countries, with a median follow-up duration of 2.9 years. Patients were randomly assigned in a 1:1:1:1 ratio to 1 of 4 treatment modes, and received either a plasma exchange and a standard-dose oral glucocorticoid regimen, a plasma exchange and a reduced-dose glucocorticoid regimen, no plasma exchange and a standard-dose glucocorticoid regimen, or no plasma exchange and a reduced-dose glucocorticoid regimen. All patients received induction immunosuppressive therapy with either cyclophosphamide or rituximab.

The per-protocol population included 338 patients (96.0%) in the plasma exchange group, 322 (91.5%) in the control group, 330 (93.5%) in the reduced-dose group, and 325 (92.6%) in the standard-dose group.

In an analysis of the primary outcome, investigators detected no interaction between the glucocorticoid regimen and the plasma exchange assignments (P =.72). Death or ESKD occurred in 28.4% (n=100/352) of patients in the plasma exchange group and 31.0% (n=109/352) in the control group (hazard ratio, 0.86 [95% CI, 0.65-1.13]; P =.27). According to results of the sensitivity analyses, the results did not substantially differ from primary analyses, and no evidence of interactions by subgroup were noted.

In the per-protocol population, death or ESKD occurred in 27.9% (n=92/330) and 25.5% (n=83/325) of patients in the reduced- and standard-dose groups, respectively. Researchers found that the reduced-dose regimen was noninferior to the standard-dose regimen in terms of primary outcomes (absolute risk difference, 2.3 percentage points [90% CI, -3.4 to 8.0 percentage points]; [95% CI, -4.5 to 9.1 percentage points], respectively). Sensitivity analysis results were similar, with death or ESKD occurring in 30.3% (n=107/353) and 29.1% (n=102/351) of reduced- and standard-dose group patients, respectively (absolute risk difference, 0.01 percentage points [95% CI, -5.1 to 5.1]).

During the period between randomization and 1 year, 142 serious infections occurred in 27.2% (n=96) of patients in the reduced-dose group, while 180 serious infections occurred in 33.0% (n=116) of the standard-dose group (incidence rate ratio, 0.69 [95% CI, 0.52-0.93]). Types and frequencies of serious adverse events were similar across both groups, although serious adverse kidney-related events were more common in the reduced-dose group (unadjusted risk ratio, 1.84 [95% CI, 1.18-2.87]). Incidence of ESKD did not differ between the groups (hazard ratio, 0.96 [95% CI, 0.68-1.34]).

Limitations included the open-label nature of the study design and the potential for bias, and the wide confidence intervals associated with some outcomes.

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“[T]he current trial did not show that the addition of plasma exchange to standard therapy conferred benefits in patients with severe ANCA-associated vasculitis, but it did show that a reduced-dose regimen of oral glucocorticoids was noninferior to a standard-dose regimen,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Walsh M, Merkel PA, Peh C-A, et al; for the PEXIVAS Investigators. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020;382(7):622-631.