Plasma exchange for severe alveolar hemorrhage in ANCA-associated vasculitis: emulation of a target trial
(2026) American Journal of Respiratory and Critical Care Medicine — (2026)
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- Authors
Sanna, Anne-Claire 
Gendreau, Ségolène Terrier, Benjamin
- Abstract
- RATIONALE : Patients with severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-related diffuse alveolar hemorrhage (DAH) face high mortality. In the PEXIVAS trial, plasma exchange (PLEX) did not reduce death or end-stage kidney disease, but only 9% had severe DAH. OBJECTIVES : This study aimed to assess whether PLEX lowers mortality in patients with severe DAH. METHODS : We emulated a target trial using retrospective data from a national multicenter cohort of patients with severe AAV-related DAH. The primary endpoint was 30-day mortality after ICU admission, analyzed using a Cox model adjusted for prespecified confounders. MAIN RESULTS : We included 184 patients (median age 66 [53–75] years; 51% female; 51% with granulomatosis with polyangiitis; 53% MPO-ANCA positive). Of these, 144 (78.3%) received PLEX and 40 (21.7%) did not. Baseline characteristics were similar, except for more severe renal impairment (creatinine 357 vs. 171 µmol/L, P = 0.01) and more frequent cyclophosphamide use (77% vs. 55%, P = 0.01) in the PLEX group. Severity at ICU admission (median SAPS II score: 42) and mechanical ventilation needs (54%) were comparable between groups. At 30 days, overall survival was 85%. No significant difference in mortality was observed between the PLEX and no-PLEX groups: 30-day survival was 85% (95% CI 81–90) with PLEX vs. 88% (95% CI 77–96) without (HR 1.23; 95% CI 0.57–3.89). Secondary outcomes were also similar. CONCLUSION : In this emulated target trial, PLEX did not reduce 30-day mortality in patients with severe AAV-related DAH.
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Citations
Sanna, A.-C., Gendreau, S., Desnos, C., Lombardi, R., Malherbe, J., Titeca-Beauport, D., Reizine, F., Louis, G., Nassarmadji, K., Campagne, J., Martellosio, J.-P., Deroux, A., Bendiab, E., Coirier, V., Catano, J., Pineton De Chambrun, M., Samson, M., Vigneron, C., Néel, A., et al. (2026). Plasma exchange for severe alveolar hemorrhage in ANCA-associated vasculitis: emulation of a target trial. American Journal of Respiratory and Critical Care Medicine. Accepted/in-press. https://doi.org/10.1093/ajrccm/aamaf122 (Original work published 2026)