Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis

M. Walsh*, P. A. Merkel, C. A. Peh, W. M. Szpirt, X. Puechal, S. Fujimoto, C. M. Hawley, N. Khalidi, O. Flosmann, R. Wald, L. P. Girard, A. Levin, G. Gregorini, L. Harper, W. F. Clark, C. Pagnoux, U. Specks, L. Smyth, V. Tesar, T. Ito-IharaJ. R. De Zoysa, W. Szczeklik, L. F. Flores-Suarez, S. Carette, L. Guillevin, C. D. Pusey, A. L. Casian, B. Brezina, A. Mazzetti, C. A. McAlear, E. Broadhurst, D. Reidlinger, S. Mehta, N. Ives, D. R.W. Jayne, PEXIVAS Investigators

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

408 Citations (Scopus)

Abstract

BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasmaexchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard- dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K.

Original languageEnglish
Pages (from-to)622-631
Number of pages10
JournalNew England Journal of Medicine
Volume382
Issue number7
DOIs
Publication statusPublished - 13 Feb 2020

Bibliographical note

Funding Information:
Supported by grants from the National Institute for Health Research, United Kingdom (HTA 08/56/04); the Food and Drug Administration (FDA R01 FD003516); the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR0573319); the National Institutes of Health of the U.S. Department of Health and Human Services; the National Health and Medical Research Council, Australia (626939, APP1086192, 631731, and APP1092957); the Canadian Institutes of Health Research (211079 and 159662); the French Ministry of Health, Programme Hospi-talier de Recherche Clinique (AOM11142); the Research Committee on Intractable Vasculitides of the Ministry of Health, Labor, and Welfare of Japan; and the Japan Agency for Medical Research and Development (AMED): the Strategic Study Group to Establish the Evidence for Intractable Vasculitis Guideline. Terumo BCT, Terumo BCT Mexico, Fresenius Medical Care Australia, Baxter Healthcare (Australia), and Asahi Kasei Medical provided in-kind plasma-exchange disposables. Dr. Walsh was supported by a New Investigator Award from the Canadian Institutes of Health Research.

Keywords

  • Administration, Oral
  • Adult
  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications
  • Combined Modality Therapy
  • Cyclophosphamide/therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Glucocorticoids/administration & dosage
  • Humans
  • Immunosuppressive Agents/therapeutic use
  • Incidence
  • Induction Chemotherapy
  • Kidney Diseases/complications
  • Kidney Failure, Chronic/epidemiology
  • Male
  • Middle Aged
  • Plasma Exchange/adverse effects
  • Rituximab/therapeutic use
  • GLOMERULONEPHRITIS
  • CYCLOPHOSPHAMIDE
  • AZATHIOPRINE
  • INDUCTION
  • MAINTENANCE THERAPY
  • RITUXIMAB
  • ALVEOLAR HEMORRHAGE
  • RANDOMIZED-TRIAL
  • REMISSION

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