PEXIVAS Trial Challenges the Benefits of Plasma Exchange, Glucocorticoid Use in ANCA-Associated Vasculitis

Findings from the largest randomized controlled trial in vasculitis indicate that plasma exchange and glucocorticoid use may not offer significant benefits to patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, according to research published in Nature Reviews Nephrology.¹

Current treatment strategies for ANCA-associated vasculitis include the use of plasma exchange to remove circulating autoantibodies and attenuate disease activity. Along with plasma exchange, glucocorticoid use is a part of the treatment strategy to induce remission in patients with ANCA-associated vasculitis. However, according to findings from the PEXIVAS trial (Plasma Exchange and Glucocorticoids for Treatment of ANCA-Associated Vasculitis; ClinicalTrials.gov Identifier: NCT00987389), plasma exchange conferred no benefits to patients with end stage kidney disease (ESKD) or diffuse alveolar hemorrhage, both of which are common in ANCA-associated vasculitis. Moreover, reductions in doses of oral glucocorticoids resulted in similar patient outcomes but with significantly reduced rates of severe infections.

The PEXIVAS trial enrolled 704 patients diagnosed with ANCA-associated vasculitis across 16 countries, with a median follow-up of 2.9 years.² Study participants were randomly assigned to receive plasma exchange or no plasma exchange (control group); participants were also randomly assigned to receive either a standard-dose or reduced-dose regimen of oral glucocorticoids. All PEXIVAS participants received an initial dose of oral steroids (50 mg, 60 mg, or 75 mg daily, based on patient weight) that was tapered after the first week and at a faster rate in the reduced-dose vs standard-dose regimen group. Cumulative oral dose was tapered to 44% lower than current standard-dose therapy at 3 months and to a 60% lower dose at 6 months. Researchers of the PEXIVAS trial followed-up with patients for up to 7 years with regard to death from any cause or ESKD.

Among patients with diffuse pulmonary hemorrhage, 26.9% in the plasma exchange group vs 27.3% in the control group died from either ESKD or any cause (severe disease: hazard ratio [HR], 0.67, 95% CI, 0.28-1.64; nonsevere disease: HR, 0.64, 95% CI, 0.33-1.24). Among patients with severe kidney disease, 28.7% in the plasma exchange group vs 29.5% in the control group died from either any cause or ESKD (HR, 0.77, 95% CI, 0.53-1.11). A total of 27.9% of patients in the reduced-dose group vs 25.5% of patients in the standard-dose group died from either ESKD or any cause. However, at 1 year, patients in the reduced-dose group vs the standard-dose group experienced fewer serious infections (incident rate ratio, 0.69, 95% CI, 0.52-0.93).

The PEXIVAS study limitations included lack of kidney biopsy samples from participants as a result of which degree of disease chronicity could not ascertained, and the small sample size.

“The lack of any demonstrable efficacy of plasma exchange in patients with severe [ANCA-associated vasculitis] questions its continued use and should guide a change in clinical practice, particularly when weighed against its associated costs,” the investigators of this research concluded. At the same time, mainstream practice can safely adopt reduced-dose glucocorticoids to minimize the adverse effects that have frequently accompanied current treatment of [ANCA-associated vasculitis].

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Morris A, Geetha D. (2020). PEXIVAS challenges current ANCA-associated vasculitis therapy [published March 13, 2020]. Nat Rev Nephrol Mar. doi:10.1038/s41581-020-0269-6 

2. Walsh M, Merkel PA, Peh CA, et al. (2020). Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 382(7):622.