TY - JOUR
T1 - Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Results of an International Randomized Controlled Trial (PEXIVAS)
AU - the PEXIVAS Investigators
AU - Fussner, Lynn A.
AU - Flores-Suárez, Luis Felipe
AU - Cartin-Ceba, Rodrigo
AU - Specks, Ulrich
AU - Cox, P. Gerard
AU - Jayne, David R.W.
AU - Merkel, Peter A.
AU - Walsh, Michael
AU - Paizis, Kathy
AU - Walters, Giles
AU - Jardine, Meg
AU - Milton, Caroline
AU - Ibraham, Abu
AU - Siva, Brian
AU - Desmond, Michael
AU - Perkovic, Vlado
AU - Kurtkoti, Jadadeesh
AU - Vilayur, Eswari
AU - Cass, Alan
AU - Summers, Shaun
AU - Brown, Fiona
AU - Ryan, Jessica
AU - Kerr, Peter
AU - Noble, Euan
AU - Luxton, Grant
AU - Mudge, David W.
AU - Hawley, Carmel
AU - Johnson, David W.
AU - Peh, Chen Au
AU - Faull, Randall J.
AU - Ranganathan, Dwarakanathan
AU - Jeffs, Lisa
AU - Nicholls, Kathy
AU - Hughes, Peter
AU - Cooper, Bruce
AU - Boudville, Neil
AU - Ford, Sharon
AU - Langham, Robyn
AU - Reidlinger, Donna
AU - Morrish, Alicia
AU - Badve, Sunil V.
AU - Pascoe, Elaine
AU - Paul-Brent, Peta Anne
AU - Robison, Laura
AU - Valks, Andrea
AU - Blockmans, Daniel
AU - Henckaerts, Liesbet
AU - Sprangers, Ben
AU - Suri, Rita
AU - Brachemi, Soumeya
AU - Clark, William
AU - Garg, Amit
AU - Carette, Simon
AU - Pagnoux, Christian
AU - Reich, Heather
AU - Barth, David
AU - Khalidi, Nader
AU - Cox, Gerry
AU - Mazzetti, Andrea
AU - Robins, Diane
AU - Wald, Ron
AU - Perl, Jeffrey
AU - Pavenski, Katerina
AU - Dacouris, Niki
AU - Levin, Adeera
AU - Copland, Michael
AU - Fairhead, Todd
AU - Pannu, Neesh
AU - Qarni, Muhammad Uwais
AU - Habib, Syed
AU - Girard, Louis
AU - Manns, Braden
AU - Tesar, Vladimir
AU - Hruskova, Zdenka
AU - Chocova, Zdenka
AU - Povlsen, Johan
AU - Gregersen, Jon
AU - Ivarsen, Per
AU - Birn, Henrik
AU - Krarup, Elizabeth
AU - Pedersen, Erling B.
AU - Thomsen, Ingrid
AU - Bech, Jesper Nørgaard
AU - Szpirt, Wladmir
AU - Egfjord, Martin
AU - Mesbah, Rafik
AU - Bataille, Pierre
AU - Rey, Isabelle
AU - Chantrel, François
AU - Vanhille, Philipe
AU - Quémeneur, Thomas
AU - Carron, Pierre Louis
AU - Zaoui, Philippe
AU - de Moreuil, Claire
AU - Gosselin, Morgane
AU - Delluc, Aurélien
AU - Hanrotel-Saliou, Catherine
AU - Le Jeune, Mathilde
AU - Ficheux, Maxence
AU - Aniort, Julien
AU - Lavigne, Christian
AU - Augusto, Jean Francois
AU - Chauveau, Dominique
AU - Guitard, Joëlle
AU - Huart, Antoine
AU - Ribes, David
AU - Gatault, Philippe
AU - Becmeur, Camille
AU - Muller, Sandrine
AU - Betz, Valérie
AU - Klein, Alexandre
AU - Blaison, Gilles
AU - Seror, Raphaele
AU - Francois, Helénè
AU - Mariette, Xavier
AU - Aubrun, Aurore
AU - Coustet, Baptiste
AU - Palazzo, Elisabeth
AU - Ottaviani, Sébastien
AU - Goulenok, Tiphaine
AU - Daugas, Eric
AU - Dieudé, Philipe
AU - Papo, Thomas
AU - Lebas, Céline
AU - Lionet, Arnaud
AU - Guillevin, Loıc
AU - Mouthon, Luc
AU - Puéchal, Xavier
AU - Jourde-Chiche, Noémie
AU - Ruivard, Marc
AU - Karras, Alexandre
AU - Limal, Nicolas
AU - Kofman, Thomas
AU - Le Quellec, Alain
AU - Maurier, François
AU - Gibelin, Aude
AU - Parrot, Antoine
AU - Bachmeyer, Claude
AU - Gombert, Bruno
AU - Nouvier, Mathilde
AU - Lega, Jean Christophe
AU - Fain, Olivier
AU - Andrès, Emmanuel
AU - Cottet, Rachel
AU - Gregorini, Gina
AU - Jeannin, Guido
AU - Possenti, Stefano
AU - Buzio, Carlo
AU - Vaglio, Augusto
AU - Oliva, Elena
AU - Makino, Hirofumi
AU - Muso, Eri
AU - Endo, Tomomi
AU - Kakita, Hiroko
AU - Suzuki, Hiroyuki
AU - Handa, Takaya
AU - Kang, Youngna
AU - Ariyasu, Yuki
AU - Tsukamoto, Tatsuo
AU - Endo, Shuichiro
AU - Miyata, Hitomi
AU - Yamada, Hiroyuki
AU - Ito-Ihara, Toshiko
AU - Uchida, Shunya
AU - Kono, Hajime
AU - Fujigaki, Yoshihide
AU - Kikuchi, Hirotoshi
AU - Nanki, Toshihiro
AU - Kato, Hideki
AU - Okamoto, Akiko
AU - Asako, Kurumi
AU - Suzuki, Kazuo
AU - Hamano, Yoshitomo
AU - Yamagata, Kunihiro
AU - Usui, Joichi
AU - Fujimoto, Shouichi
AU - Sato, Yuji
AU - Kikuchi, Masao
AU - Sánchez-Guerrero, Sergio A.
AU - Collins, Michael
AU - Schollum, John
AU - de Zoysa, Janak
AU - Quincy, Vicki
AU - Sizeland, Peter
AU - Aasarod, Knut
AU - Solbu, Marit
AU - Bruun, Trude Jannecke
AU - Koldingsnes, Wenche
AU - Wludarczyk, Anna
AU - Nowak, Ilona
AU - Gorka, Jacek
AU - Sznajd, Jan
AU - Padjas, Agnieszka
AU - Jankowski, Milosz
AU - Widawska, Agnieszka
AU - Szczeklik, Wojciech
AU - Ballarin, Jose
AU - Bruchfeld, Annette
AU - Efvergren, Mats
AU - Eriksson, Per
AU - Westman, Kerstin
AU - Selga, Daina
AU - Heijl, Caroline
AU - Ohlsson, Sophie
AU - Segelmark, Marten
AU - Basu, Neil
AU - Kidder, Dana
AU - Fluck, Nicholas
AU - Smith, Rona
AU - Wilcocks, Lisa
AU - McClure, Mark
AU - Jones, Rachel
AU - Trivedi, Sapna
AU - Gopaluni, Seerapani
AU - Brettell, Elizabeth
AU - Crump, Paul
AU - Feilbach, Annika
AU - Hewitt, Catherine
AU - Hilken, Nick
AU - Howman, Andrew
AU - Hughes, Terry
AU - Ives, Natalie
AU - Jarrett, Hugh
AU - Mehta, Samir
AU - Record, Rebecca
AU - Ryan, Gemma
AU - Sidile, Chaka
AU - Wheatley, Keith
AU - Sheerin,
AU - Brown, Alison
AU - Baines, Laura Anne
AU - Lordan, Jim
AU - Pusey, Charles
AU - Tanna, Anisha
AU - McAdoo, Stephen
AU - Levy, Jeremy
AU - Griffith, Megan
AU - Klebe, Bernhard
AU - Doulton, Timothy
AU - Warwick, Graham
AU - Burton, James
AU - Barratt, Jonathon
AU - Topham, Peter
AU - Baines, Richard
AU - Brunskill, Nigel
AU - Al-Jayyousi, Reem
AU - Hamilton, Patrick
AU - Patel, Mumtaz
AU - Mitra, Sandip
AU - Brown, Nina
N1 - Publisher Copyright:
Copyright © 2024 by the American Thoracic Society.
PY - 2024/5/1
Y1 - 2024/5/1
N2 - 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.
AB - 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.
KW - diffuse alveolar hemorrhage
KW - glucocorticoids
KW - plasma exchange
KW - respiratory failure
UR - http://www.scopus.com/inward/record.url?scp=85192028427&partnerID=8YFLogxK
U2 - 10.1164/rccm.202308-1426OC
DO - 10.1164/rccm.202308-1426OC
M3 - Article
C2 - 38346237
AN - SCOPUS:85192028427
SN - 1073-449X
VL - 209
SP - 1141
EP - 1151
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 9
ER -