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evident
Original paper
2020NEJMRheumatology/Immunology

PEXIVAS

Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis

RCTANCA-associated vasculitis

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Overview

In severe ANCA vasculitis, plasma exchange did not reduce death or ESKD; reduced-dose glucocorticoids were noninferior to a standard-dose regimen.

Clinical takeaway

Do not add plasma exchange to improve death or ESKD in severe ANCA-associated vasculitis defined by eGFR under 50 or diffuse pulmonary hemorrhage. A reduced-dose oral glucocorticoid regimen was noninferior for that same composite. Fewer serious infections at 1 year is a secondary finding.

Key result

Death or ESKD occurred in 28.4% with plasma exchange versus 31.0% without it (HR 0.86, 95% CI 0.65-1.13; P=0.27). Reduced-dose glucocorticoids were noninferior to standard-dose for the same composite (27.9% vs 25.5%; risk difference 2.3 percentage points, 90% CI -3.4 to 8.0).

Practice impact

Skip routine plasma exchange for death/ESKD prevention; a reduced-dose steroid taper is an acceptable alternative to standard-dose.

Evidence

Study design

Randomized trial with a 2-by-2 factorial design comparing plasma exchange versus no plasma exchange and a reduced-dose versus standard-dose oral glucocorticoid regimen.

Enrollment

704

Follow-up

Up to 7 years for the primary composite of death or end-stage kidney disease.

Geography

Not listed

Clinical question

In severe ANCA-associated vasculitis, does plasma exchange reduce death or ESKD, and is a reduced-dose oral glucocorticoid regimen noninferior to a standard-dose regimen for that outcome?

Population

  • Patients with severe ANCA-associated vasculitis, defined by an estimated glomerular filtration rate under 50 ml per minute per 1.73 m2 or diffuse pulmonary hemorrhage.
  • The plasma-exchange comparison included 352 patients in each group (704). The glucocorticoid comparison included 330 in the reduced-dose group and 325 in the standard-dose group.

Intervention

Plasma exchange (seven exchanges within 14 days after randomization) and, in the factorial glucocorticoid comparison, a reduced-dose oral glucocorticoid regimen.

Comparator

No plasma exchange. In the glucocorticoid comparison, a standard-dose oral glucocorticoid regimen, using a noninferiority margin of 11 percentage points.

Primary outcome

Composite of death from any cause or end-stage kidney disease (ESKD).

Plasma exchange did not reduce death or ESKD (HR 0.86, 95% CI 0.65-1.13; P=0.27). Separately, a reduced-dose oral glucocorticoid regimen was noninferior to a standard-dose regimen for the same composite (risk difference 2.3 percentage points, 90% CI -3.4 to 8.0).

Hazard ratio / 0.86 / 95% CI 0.65-1.13 / p=0.27

Key results

  • Plasma exchange: death or ESKD occurred in 100 of 352 patients (28.4%) versus 109 of 352 (31.0%) without plasma exchange (HR 0.86, 95% CI 0.65-1.13; P=0.27). Results were similar in subgroup analyses and secondary outcomes.
  • Reduced-dose versus standard-dose glucocorticoids: death or ESKD occurred in 92 of 330 (27.9%) versus 83 of 325 (25.5%); absolute risk difference 2.3 percentage points (90% CI -3.4 to 8.0), which met the 11-percentage-point noninferiority margin.
  • Serious infections at 1 year, a secondary outcome, were less common with reduced-dose glucocorticoids (incidence rate ratio 0.69, 95% CI 0.52-0.93). Other secondary outcomes were similar between glucocorticoid groups.

Harms

  • Serious infections at 1 year were less common with the reduced-dose glucocorticoid regimen than with the standard-dose regimen (incidence rate ratio 0.69, 95% CI 0.52-0.93).

Clinical Use

Practice impact

  • Do not use plasma exchange expecting fewer deaths or less ESKD in severe ANCA-associated vasculitis as defined here.
  • A reduced-dose oral glucocorticoid regimen can replace a standard-dose regimen for the death-or-ESKD composite and was associated with fewer serious infections at 1 year.

Applicability

  • Most applicable to severe ANCA-associated vasculitis with eGFR under 50 ml/min/1.73 m2 or diffuse pulmonary hemorrhage.

Limitations

  • The plasma-exchange comparison used 704 patients (352 vs 352); the glucocorticoid comparison used 655 (330 vs 325). The abstract does not explain the smaller glucocorticoid N.
  • Glucocorticoid noninferiority used a 90% confidence interval and an 11-percentage-point margin, not a superiority test.
  • Follow-up was up to 7 years; a single median follow-up is not reported.

Common misinterpretations

  • A hazard ratio of 0.86 is not a proven benefit; the 95% CI included no effect.
  • Noninferiority of reduced-dose steroids is not superiority; the reduced-dose arm had a slightly higher point estimate for death or ESKD.
  • Fewer serious infections at 1 year is a secondary glucocorticoid finding, not the primary result.

Related evidence

RAVE - Earlier Trial

Citation

Walsh M, Merkel PA, Peh CA, et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020;382(7):622-631. doi:10.1056/NEJMoa1803537

Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD.