Plasma Exchange Does Not Provide Additional Benefit in Severe ANCA-Associated Vasculitis
Vikas Majithia, MD, MPH
Chief and Fellowship Program Director, Division of Rheumatology, University of Mississippi School of Medicine and Medical Center
Citation: Majithia V. Plasma Exchange Does Not Provide Additional Benefit in Severe ANCA-Associated Vasculitis. [Published online November 27, 2018]. Rheumatology Consultant.
The PEXIVAS study was presented at the annual meeting of American College of Rheumatology by Dr. Peter Merkel who heads the National Institutes of Health–supported Vasculitis Clinical Research Consortium. It is the largest randomized trial ever done in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) to evaluate the role of both plasma exchange and oral glucocorticoid dosing in patients with AAV.
AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. There is a 50% mortality rate within the first year of diagnosis due to infection and much of it is associated with current high oral glucocorticoid doses in AAV.
The trial was done in a multicenter, international, open-label, randomized, 2-by-2 factorial design, essentially combining two trials within a single protocol. The trial population comprised of 704 patients with severe AAV disease either granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). To qualify as having severe AAV, participants had to have new or relapsing disease with an estimated glomerular filtration rate below 50 mL/min/1.73 m2 and/or lung hemorrhage.
The patients underwent induction therapy with either IV or oral cyclophosphamide or rituximab along with IV methylprednisolone based on local investigators preference and local protocols. They were then randomized to either receiving 7 plasma exchange sessions over 2 weeks or no plasma exchange. Further randomization was performed to a standard weight-based regimen or a reduced-dose regimen of oral glucocorticoids. Cumulative amount of glucocorticoid use in the reduced-dose regimen was about 60% less over the course of 6 months as compared to the standard-dose regimen. Total duration of follow-up ranged from 1 to 7 years.
Composite primary endpoint—all-cause mortality or end-stage renal disease—occurred in 28% of patients who received plasma exchange and 31% of those who did not receive plasma exchange; the difference was not statistically significant (hazard ratio = 0.86; 95% confidence interval [CI], 0.65-1.13). There was no difference in the outcomes based on the prespecified subgroups categorized by age, creatinine clearance, ANCA type, immunosuppression, or alveolar hemorrhage.
The trial results highlight that plasma exchange did not prevent composite endpoint of all-cause mortality or end-stage renal disease, raising doubt about its role in severe AAV.
At the same time, reduced steroid-dose regimen was as effective as the commonly used higher standard-dose regimen while significantly reducing the serious infection rate; composite endpoint was achieved in 28% of patients in the reduced glucocorticoid group and 26% in the standard glucocorticoid group (absolute risk difference = 2.3%; 95% CI, -3.4-8). Prespecified end point of serious infection in the first year occurred in 27% of those treated with reduced-dose regimen compared with 33% in those treated with standard dose therapy (incidence rate ratio = 0.70; 95% CI, 0.52-0.94). The role of plasma exchange in those receiving dialysis was not studied in the trial and remains unclear.
In summary, plasma exchange was not beneficial for treatment of severe ANCA-associated vasculitis while a reduced-dose glucocorticoid regimen was as effective as the standard-dose regimen and had fewer serious infections in the largest randomized trial yet conducted in this disease state. These results are likely to have a strong and immediate impact in changing the way we approach and treat these patients, reduce cost as well as complications and improve their outcomes.
The study was sponsored by the National Institutes of Health, the Food and Drug Administration, the U.K. Medical Research Council and the National Institute for Health Research, the Canadian Institutes of Health Research, and the governments of France, Australia, and New Zealand.
Walsh M, Peter A. Merkel PA, Jayne D. The effects of plasma exchange and reduced-dose glucocorticoids during remission-induction for treatment of severe ANCA-associated vasculitis. Paper presented at: 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago IL. . Accessed November 27, 2018.