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; ClinicalTrials.gov 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.
“[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.