Management of anti-neutrophil cytoplasmic antibody–associated alveolar hemorrhage: A Bayesian reanalysis of the PEXIVAS trial

OBJECTIVE: The PEXIVAS trial evaluated plasma exchange (PLEX) and glucocorticoid dose in antineutrophil-cytoplasmic antibody-associated vasculitis (AAV). We reanalyzed PEXIVAS using Bayesian methods to focus on patients with diffuse alveolar hemorrhage (DAH). METHODS: In the original trial, adults with AAV with kidney injury and/or DAH were randomized to PLEX or no PLEX and reduced- or standard-dose glucocorticoids. We evaluated 1-year survival and severe infection among participants with DAH, no DAH, and severe DAH (oxygen saturation ≤85% on room air or mechanical ventilation) across multiple priors. Secondary outcome included severe infection (leading to hospitalization, intravenous antibiotics, or death). We calculated hazard ratios (HR) for survival and odds ratios (OR) for infection, 95% credible intervals (CrI), and probabilities of survival benefit (HR<1) and infection (OR>1). RESULTS: Among 704 participants (191 with DAH, 61 with severe DAH), using uninformative priors, the probability of improved survival was 93% for participants with DAH receiving PLEX (HR 0.52, 95% CrI 0.21-1.26) and 67% without DAH (HR 0.86, 95% CrI 0.43-1.71). Participants receiving reduced-dose glucocorticoids had 98% probability of improved survival without DAH (HR 0.46, 95% CrI 0.22-0.95) but 12% with severe DAH (HR 2.02, 95% CrI 0.64-6.35). PLEX increased severe infection odds (OR 1.25, 95% CrI 0.92-1.70; 92% probability OR>1), whereas reduced-dose glucocorticoids decreased infection odds (OR 0.85, 95% CrI 0.63- 1.15; 85% probability OR<1). Results were consistent across priors. CONCLUSION: Patients with AAV and DAH may benefit from PLEX. Reduced-dose glucocorticoids improve survival for individuals without DAH, but may be harmful in patients with severe DAH.