Background/Purpose: It is uncertain whether plasma exchange improves clinical outcomes in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.  Also uncertain is whether, compared to standard therapy with high-dose oral glucocorticoids, a lower-dose glucocorticoid regimen reduces the risk of infection without increasing the risk of end-stage renal disease or death.  The PEXIVAS clinical trial addressed both of these questions.

Methods: PEXIVAS was a 2-by-2 factorial, randomized, controlled trial to separately evaluate plasma exchange and two different regimens of oral glucocorticoids in patients with new or relapsing severe ANCA-associated vasculitis, including lung hemorrhage and/or glomerulonephritis (eGFR <50 ml/min/1.73 m2).  Participants were randomly assigned to 7 treatments of plasma exchange or no plasma exchange.  Participants were also randomly assigned to either a standard-dose oral glucocorticoid regimen or a reduced-dose oral glucocorticoid regimen (<60% of the standard regimen by 6 months).  All patients received immunosuppression with either cyclophosphamide or rituximab.  Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage renal disease.

Results: The trial recruited 704 participants from 98 sites in 15 countries: 397 (56%) men; 289 (41%) PR3-ANCA, 209 (59%) MPO-ANCA; 691 (98%) with renal involvement; 191 (27%) with alveolar hemorrhage.  109 (15%) patients received rituximab and 595 (85%) received cyclophosphamide.

Among 704 participants, the primary outcome occurred in 28% of patients allocated to plasma exchange compared to 31% in the no plasma exchange group (hazard ratio 0.86, 95% confidence interval [CI] 0.65 to 1.13; p=0.27).  The primary outcome occurred in 28% of patients in the reduced glucocorticoid group and 26% in the standard glucocorticoid group (absolute risk difference 2.3%, 90% CI -3.4% to 8.0%; met non-inferiority hypothesis).  Serious infections in the first year occurred less often in the reduced glucocorticoid group compared to the standard group (incidence rate ratio 0.70, 95% CI 0.52 to 0.94; p=0.02).  The results were similar for both the plasma exchange and glucocorticoid interventions when the individual outcomes of end-stage renal disease or death were analyzed separately. 

Conclusion: Plasma exchange does not reduce the risk of end-stage renal disease or death in patients with ANCA-associated vasculitis.  Compared to a standard dose, reduced glucocorticoids did not substantially increase the risk of death or end-stage renal disease and resulted in fewer serious infections. 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 ANCA-associated vasculitis.