Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS)

Am J Respir Crit Care Med. 2024 May 1;209(9):1141-1151. doi: 10.1164/rccm.202308-1426OC.

Abstract

Rationale: Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The PEXIVAS (Plasma Exchange and Glucocorticoids in Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis) (NCT00987389) trial was the largest in AAV and the first to enroll participants with DAH requiring mechanical ventilation. Objectives: Evaluate characteristics, treatment effects, and outcomes for patients with AAV with and without DAH. Methods: PEXIVAS randomized 704 participants to plasma exchange (PLEX) or no-PLEX and reduced or standard-dose glucocorticoids (GC). DAH status was defined at enrollment as no-DAH, nonsevere, or severe (room air oxygen saturation of ⩽ 85% as measured by pulse oximetry, or use of mechanical ventilation). Measurements and Main Results: At enrollment, 191 (27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3 (proteinase 3)-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH (n = 513; 72.9%). Among those with DAH, 8/95 (8.4%) receiving PLEX died within 1 year versus 15/96 (15.6%) with no-PLEX (hazard ratio, 0.52; confidence interval [CI], 0.21-1.24), whereas 13/96 (13.5%) receiving reduced GC died versus 10/95 (10.5%) with standard GC (hazard ratio, 1.33; CI, 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX versus no-PLEX (medians, 25; interquartile range [IQR], 22-26 vs. 22-27) and fewer with reduced GC (median, 23; IQR, 20-25) versus standard GC (median, 26; IQR, 25-28). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within 1 year versus 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Conclusions: Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Original clinical trial registered with www.clinicaltrials.gov (NCT00987389).

Keywords: diffuse alveolar hemorrhage; glucocorticoids; plasma exchange; respiratory failure.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis* / complications
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis* / drug therapy
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis* / mortality
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis* / therapy
  • Female
  • Glucocorticoids* / therapeutic use
  • Hemorrhage* / etiology
  • Hemorrhage* / therapy
  • Humans
  • Lung Diseases / etiology
  • Lung Diseases / therapy
  • Male
  • Middle Aged
  • Plasma Exchange* / methods
  • Pulmonary Alveoli
  • Respiration, Artificial / statistics & numerical data
  • Treatment Outcome

Substances

  • Glucocorticoids

Associated data

  • ClinicalTrials.gov/NCT00987389