PEXIVAS: No benefit of plasma exchange in ANCA-associated vasculitis
medwireNews: The addition of plasma exchange to standard therapy does not reduce the risk for all-cause mortality or end-stage renal disease (ESRD) among patients with severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, suggest findings from the PEXIVAS trial.
However, the trial did demonstrate that a reduced-dose regimen of glucocorticoids is noninferior to a standard-dose protocol, while reducing the risk for serious infections, report Michael Walsh (McMaster University–Hamilton Health Sciences, Ontario, Canada) and co-investigators in The New England Journal of Medicine.
The open-label trial with a two-by-two factorial design included 704 patients with severe ANCA-associated vasculitis (estimated glomerular filtration rate <50 mL/min per 1.73 m2 or diffuse pulmonary hemorrhage) who received standard induction immunosuppressive therapy with either cyclophosphamide or rituximab.
The patients were randomly assigned to undergo seven plasma exchange treatments over 14 days or no plasma exchange, as well as to receive a reduced-dose (50% reduction at the start of week 2) or standard-dose (gradual tapering from around week 3) glucocorticoid regimen; the cumulative dose of glucocorticoids in the reduced-dose arm was less than 60% of that in patients given the standard-dose regimen at 6 months.
This trial design “allowed separate evaluations of initial treatment with plasma exchange as compared with no plasma exchange (with either cyclophosphamide or rituximab administered to all patients) and of two different regimens of oral glucocorticoids,” explain Walsh and team.
In all, 28.4% of 352 patients who received plasma exchange experienced the primary endpoint of death or ESRD over a median follow-up of 2.9 years, as did 31.0% of 352 patients who did not, a nonsignificant difference.
Rates of the primary endpoint were also comparable among the 330 participants given reduced-dose glucocorticoids and the 325 given the standard-dose regimen, at 27.9% and 25.5%, respectively, giving an absolute risk difference of 2.3 percentage points that met noninferiority criteria.
In the analysis of secondary outcomes, rates of serious infection over 1 year were significantly lower in the reduced-dose than the standard-dose arm, at 27.2% versus 33.0% (incidence rate ratio=0.69), but rates of death from any cause, ESRD, sustained remission, and serious adverse events were comparable in the two groups.
“[S]howing, within the limits of precision that we could estimate, that reduced-dose regimen decreased the risk of serious infections without increasing the risk of other adverse events represents an important step toward standardizing care,” say the PEXIVAS investigators.
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