Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Results of an International Randomized Controlled Trial (PEXIVAS)
(2024) In American Journal of Respiratory and Critical Care Medicine 209(9). p.1141-1151- 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%... (More)
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.
(Less)
- author
- Fussner, Lynn A. ; Flores-Suárez, Luis Felipe ; Cartin-Ceba, Rodrigo ; Specks, Ulrich ; Cox, P. Gerard ; Jayne, David R.W. ; Merkel, Peter A. and Walsh, Michael
- contributor
- Johnson, David W.
LU
; Westman, Kerstin
LU
; Selga, Daina
LU
; Heijl, Caroline
LU
; Ohlsson, Sophie
LU
and Segelmark, Marten LU
- author collaboration
- publishing date
- 2024-05-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- diffuse alveolar hemorrhage, glucocorticoids, plasma exchange, respiratory failure
- in
- American Journal of Respiratory and Critical Care Medicine
- volume
- 209
- issue
- 9
- pages
- 1141 - 1151
- publisher
- American Thoracic Society
- external identifiers
-
- pmid:38346237
- scopus:85192028427
- ISSN
- 1073-449X
- DOI
- 10.1164/rccm.202308-1426OC
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: Copyright © 2024 by the American Thoracic Society.
- id
- 0852fa41-448c-4957-a79d-2726e0d26ba9
- date added to LUP
- 2024-08-27 14:49:32
- date last changed
- 2024-08-28 14:17:50
@article{0852fa41-448c-4957-a79d-2726e0d26ba9, abstract = {{<p>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.</p>}}, author = {{Fussner, Lynn A. and Flores-Suárez, Luis Felipe and Cartin-Ceba, Rodrigo and Specks, Ulrich and Cox, P. Gerard and Jayne, David R.W. and Merkel, Peter A. and Walsh, Michael}}, issn = {{1073-449X}}, keywords = {{diffuse alveolar hemorrhage; glucocorticoids; plasma exchange; respiratory failure}}, language = {{eng}}, month = {{05}}, number = {{9}}, pages = {{1141--1151}}, publisher = {{American Thoracic Society}}, series = {{American Journal of Respiratory and Critical Care Medicine}}, title = {{Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Results of an International Randomized Controlled Trial (PEXIVAS)}}, url = {{http://dx.doi.org/10.1164/rccm.202308-1426OC}}, doi = {{10.1164/rccm.202308-1426OC}}, volume = {{209}}, year = {{2024}}, }