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

the PEXIVAS Investigators; Lynn A. Fussner; Luis Felipe Flores-Suárez; Rodrigo Cartin-Ceba; Ulrich Specks; P. Gerard Cox; David R.W. Jayne; Peter A. Merkel; Michael Walsh; Kathy Paizis; Giles Walters; Meg Jardine; Caroline Milton; Abu Ibraham; Brian Siva; Michael Desmond; Vlado Perkovic; Jadadeesh Kurtkoti; Eswari Vilayur; Alan Cass; Shaun Summers; Fiona Brown; Jessica Ryan; Peter Kerr; Euan Noble; Grant Luxton; David W. Mudge; Carmel Hawley; David W. Johnson; Chen Au Peh; Randall J. Faull; Dwarakanathan Ranganathan; Lisa Jeffs; Kathy Nicholls; Peter Hughes; Bruce Cooper; Neil Boudville; Sharon Ford; Robyn Langham; Donna Reidlinger; Alicia Morrish; Sunil V. Badve; Elaine Pascoe; Peta Anne Paul-Brent; Laura Robison; Andrea Valks; Daniel Blockmans; Liesbet Henckaerts; Ben Sprangers; Rita Suri; Soumeya Brachemi; William Clark; Amit Garg; Simon Carette; Christian Pagnoux; Heather Reich; David Barth; Nader Khalidi; Gerry Cox; Andrea Mazzetti; Diane Robins; Ron Wald; Jeffrey Perl; Katerina Pavenski; Niki Dacouris; Adeera Levin; Michael Copland; Todd Fairhead; Neesh Pannu; Muhammad Uwais Qarni; Syed Habib; Louis Girard; Braden Manns; Vladimir Tesar; Zdenka Hruskova; Zdenka Chocova; Johan Povlsen; Jon Gregersen; Per Ivarsen; Henrik Birn; Elizabeth Krarup; Erling B. Pedersen; Ingrid Thomsen; Jesper Nørgaard Bech; Wladmir Szpirt; Martin Egfjord; Rafik Mesbah; Pierre Bataille; Isabelle Rey; François Chantrel; Philipe Vanhille; Thomas Quémeneur; Pierre Louis Carron; Philippe Zaoui; Claire de Moreuil; Morgane Gosselin; Aurélien Delluc; Catherine Hanrotel-Saliou; Mathilde Le Jeune; Maxence Ficheux; Julien Aniort; Christian Lavigne; Jean Francois Augusto; Dominique Chauveau; Joëlle Guitard; Antoine Huart; David Ribes; Philippe Gatault; Camille Becmeur; Sandrine Muller; Valérie Betz; Alexandre Klein; Gilles Blaison; Raphaele Seror; Helénè Francois; Xavier Mariette; Aurore Aubrun; Baptiste Coustet; Elisabeth Palazzo; Sébastien Ottaviani; Tiphaine Goulenok; Eric Daugas; Philipe Dieudé; Thomas Papo; Céline Lebas; Arnaud Lionet; Loıc Guillevin; Luc Mouthon; Xavier Puéchal; Noémie Jourde-Chiche; Marc Ruivard; Alexandre Karras; Nicolas Limal; Thomas Kofman; Alain Le Quellec; François Maurier; Aude Gibelin; Antoine Parrot; Claude Bachmeyer; Bruno Gombert; Mathilde Nouvier; Jean Christophe Lega; Olivier Fain; Emmanuel Andrès; Rachel Cottet; Gina Gregorini; Guido Jeannin; Stefano Possenti; Carlo Buzio; Augusto Vaglio; Elena Oliva; Hirofumi Makino; Eri Muso; Tomomi Endo; Hiroko Kakita; Hiroyuki Suzuki; Takaya Handa; Youngna Kang; Yuki Ariyasu; Tatsuo Tsukamoto; Shuichiro Endo; Hitomi Miyata; Hiroyuki Yamada; Toshiko Ito-Ihara; Shunya Uchida; Hajime Kono; Yoshihide Fujigaki; Hirotoshi Kikuchi; Toshihiro Nanki; Hideki Kato; Akiko Okamoto; Kurumi Asako; Kazuo Suzuki; Yoshitomo Hamano; Kunihiro Yamagata; Joichi Usui; Shouichi Fujimoto; Yuji Sato; Masao Kikuchi; Sergio A. Sánchez-Guerrero; Michael Collins; John Schollum; Janak de Zoysa; Vicki Quincy; Peter Sizeland; Knut Aasarod; Marit Solbu; Trude Jannecke Bruun; Wenche Koldingsnes; Anna Wludarczyk; Ilona Nowak; Jacek Gorka; Jan Sznajd; Agnieszka Padjas; Milosz Jankowski; Agnieszka Widawska; Wojciech Szczeklik; Jose Ballarin; Annette Bruchfeld; Tingting Li; Richard Brasington

doi:10.1164/rccm.202308-1426OC

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

the PEXIVAS Investigators, Lynn A. Fussner, Luis Felipe Flores-Suárez, Rodrigo Cartin-Ceba, Ulrich Specks, P. Gerard Cox, David R.W. Jayne, Peter A. Merkel, Michael Walsh, Kathy Paizis, Giles Walters, Meg Jardine, Caroline Milton, Abu Ibraham, Brian Siva, Michael Desmond, Vlado Perkovic, Jadadeesh Kurtkoti, Eswari Vilayur, Alan CassShaun Summers, Fiona Brown, Jessica Ryan, Peter Kerr, Euan Noble, Grant Luxton, David W. Mudge, Carmel Hawley, David W. Johnson, Chen Au Peh, Randall J. Faull, Dwarakanathan Ranganathan, Lisa Jeffs, Kathy Nicholls, Peter Hughes, Bruce Cooper, Neil Boudville, Sharon Ford, Robyn Langham, Donna Reidlinger, Alicia Morrish, Sunil V. Badve, Elaine Pascoe, Peta Anne Paul-Brent, Laura Robison, Andrea Valks, Daniel Blockmans, Liesbet Henckaerts, Ben Sprangers, Rita Suri, Soumeya Brachemi, William Clark, Amit Garg, Simon Carette, Christian Pagnoux, Heather Reich, David Barth, Nader Khalidi, Gerry Cox, Andrea Mazzetti, Diane Robins, Ron Wald, Jeffrey Perl, Katerina Pavenski, Niki Dacouris, Adeera Levin, Michael Copland, Todd Fairhead, Neesh Pannu, Muhammad Uwais Qarni, Syed Habib, Louis Girard, Braden Manns, Vladimir Tesar, Zdenka Hruskova, Zdenka Chocova, Johan Povlsen, Jon Gregersen, Per Ivarsen, Henrik Birn, Elizabeth Krarup, Erling B. Pedersen, Ingrid Thomsen, Jesper Nørgaard Bech, Wladmir Szpirt, Martin Egfjord, Rafik Mesbah, Pierre Bataille, Isabelle Rey, François Chantrel, Philipe Vanhille, Thomas Quémeneur, Pierre Louis Carron, Philippe Zaoui, Claire de Moreuil, Morgane Gosselin, Aurélien Delluc, Catherine Hanrotel-Saliou, Mathilde Le Jeune, Maxence Ficheux, Julien Aniort, Christian Lavigne, Jean Francois Augusto, Dominique Chauveau, Joëlle Guitard, Antoine Huart, David Ribes, Philippe Gatault, Camille Becmeur, Sandrine Muller, Valérie Betz, Alexandre Klein, Gilles Blaison, Raphaele Seror, Helénè Francois, Xavier Mariette, Aurore Aubrun, Baptiste Coustet, Elisabeth Palazzo, Sébastien Ottaviani, Tiphaine Goulenok, Eric Daugas, Philipe Dieudé, Thomas Papo, Céline Lebas, Arnaud Lionet, Loıc Guillevin, Luc Mouthon, Xavier Puéchal, Noémie Jourde-Chiche, Marc Ruivard, Alexandre Karras, Nicolas Limal, Thomas Kofman, Alain Le Quellec, François Maurier, Aude Gibelin, Antoine Parrot, Claude Bachmeyer, Bruno Gombert, Mathilde Nouvier, Jean Christophe Lega, Olivier Fain, Emmanuel Andrès, Rachel Cottet, Gina Gregorini, Guido Jeannin, Stefano Possenti, Carlo Buzio, Augusto Vaglio, Elena Oliva, Hirofumi Makino, Eri Muso, Tomomi Endo, Hiroko Kakita, Hiroyuki Suzuki, Takaya Handa, Youngna Kang, Yuki Ariyasu, Tatsuo Tsukamoto, Shuichiro Endo, Hitomi Miyata, Hiroyuki Yamada, Toshiko Ito-Ihara, Shunya Uchida, Hajime Kono, Yoshihide Fujigaki, Hirotoshi Kikuchi, Toshihiro Nanki, Hideki Kato, Akiko Okamoto, Kurumi Asako, Kazuo Suzuki, Yoshitomo Hamano, Kunihiro Yamagata, Joichi Usui, Shouichi Fujimoto, Yuji Sato, Masao Kikuchi, Sergio A. Sánchez-Guerrero, Michael Collins, John Schollum, Janak de Zoysa, Vicki Quincy, Peter Sizeland, Knut Aasarod, Marit Solbu, Trude Jannecke Bruun, Wenche Koldingsnes, Anna Wludarczyk, Ilona Nowak, Jacek Gorka, Jan Sznajd, Agnieszka Padjas, Milosz Jankowski, Agnieszka Widawska, Wojciech Szczeklik, Jose Ballarin, Annette Bruchfeld, Tingting Li, Richard Brasington

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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 language	English
Pages (from-to)	1141-1151
Number of pages	11
Journal	American journal of respiratory and critical care medicine
Volume	209
Issue number	9
DOIs	https://doi.org/10.1164/rccm.202308-1426OC
State	Published - May 1 2024

Keywords

diffuse alveolar hemorrhage
glucocorticoids
plasma exchange
respiratory failure

Access to Document

10.1164/rccm.202308-1426OC

Cite this

the PEXIVAS Investigators, Fussner, L. A., Flores-Suárez, L. F., Cartin-Ceba, R., Specks, U., Cox, P. G., Jayne, D. R. W., Merkel, P. A., Walsh, M., Paizis, K., Walters, G., Jardine, M., Milton, C., Ibraham, A., Siva, B., Desmond, M., Perkovic, V., Kurtkoti, J., Vilayur, E., ... Brasington, R. (2024). Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Results of an International Randomized Controlled Trial (PEXIVAS). American journal of respiratory and critical care medicine, 209(9), 1141-1151. https://doi.org/10.1164/rccm.202308-1426OC

@article{07c3bd816db6423cb265457c25c4f907,

title = "Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Results of an International Randomized Controlled Trial (PEXIVAS)",

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.",

keywords = "diffuse alveolar hemorrhage, glucocorticoids, plasma exchange, respiratory failure",

author = "{the PEXIVAS Investigators} and Fussner, {Lynn A.} and Flores-Su{\'a}rez, {Luis Felipe} and Rodrigo Cartin-Ceba and Ulrich Specks and Cox, {P. Gerard} and Jayne, {David R.W.} and Merkel, {Peter A.} and Michael Walsh and Kathy Paizis and Giles Walters and Meg Jardine and Caroline Milton and Abu Ibraham and Brian Siva and Michael Desmond and Vlado Perkovic and Jadadeesh Kurtkoti and Eswari Vilayur and Alan Cass and Shaun Summers and Fiona Brown and Jessica Ryan and Peter Kerr and Euan Noble and Grant Luxton and Mudge, {David W.} and Carmel Hawley and Johnson, {David W.} and Peh, {Chen Au} and Faull, {Randall J.} and Dwarakanathan Ranganathan and Lisa Jeffs and Kathy Nicholls and Peter Hughes and Bruce Cooper and Neil Boudville and Sharon Ford and Robyn Langham and Donna Reidlinger and Alicia Morrish and Badve, {Sunil V.} and Elaine Pascoe and Paul-Brent, {Peta Anne} and Laura Robison and Andrea Valks and Daniel Blockmans and Liesbet Henckaerts and Ben Sprangers and Rita Suri and Soumeya Brachemi and William Clark and Amit Garg and Simon Carette and Christian Pagnoux and Heather Reich and David Barth and Nader Khalidi and Gerry Cox and Andrea Mazzetti and Diane Robins and Ron Wald and Jeffrey Perl and Katerina Pavenski and Niki Dacouris and Adeera Levin and Michael Copland and Todd Fairhead and Neesh Pannu and Qarni, {Muhammad Uwais} and Syed Habib and Louis Girard and Braden Manns and Vladimir Tesar and Zdenka Hruskova and Zdenka Chocova and Johan Povlsen and Jon Gregersen and Per Ivarsen and Henrik Birn and Elizabeth Krarup and Pedersen, {Erling B.} and Ingrid Thomsen and Bech, {Jesper N{\o}rgaard} and Wladmir Szpirt and Martin Egfjord and Rafik Mesbah and Pierre Bataille and Isabelle Rey and Fran{\c c}ois Chantrel and Philipe Vanhille and Thomas Qu{\'e}meneur and Carron, {Pierre Louis} and Philippe Zaoui and {de Moreuil}, Claire and Morgane Gosselin and Aur{\'e}lien Delluc and Catherine Hanrotel-Saliou and {Le Jeune}, Mathilde and Maxence Ficheux and Julien Aniort and Christian Lavigne and Augusto, {Jean Francois} and Dominique Chauveau and Jo{\"e}lle Guitard and Antoine Huart and David Ribes and Philippe Gatault and Camille Becmeur and Sandrine Muller and Val{\'e}rie Betz and Alexandre Klein and Gilles Blaison and Raphaele Seror and Hel{\'e}n{\`e} Francois and Xavier Mariette and Aurore Aubrun and Baptiste Coustet and Elisabeth Palazzo and S{\'e}bastien Ottaviani and Tiphaine Goulenok and Eric Daugas and Philipe Dieud{\'e} and Thomas Papo and C{\'e}line Lebas and Arnaud Lionet and Loıc Guillevin and Luc Mouthon and Xavier Pu{\'e}chal and No{\'e}mie Jourde-Chiche and Marc Ruivard and Alexandre Karras and Nicolas Limal and Thomas Kofman and {Le Quellec}, Alain and Fran{\c c}ois Maurier and Aude Gibelin and Antoine Parrot and Claude Bachmeyer and Bruno Gombert and Mathilde Nouvier and Lega, {Jean Christophe} and Olivier Fain and Emmanuel Andr{\`e}s and Rachel Cottet and Gina Gregorini and Guido Jeannin and Stefano Possenti and Carlo Buzio and Augusto Vaglio and Elena Oliva and Hirofumi Makino and Eri Muso and Tomomi Endo and Hiroko Kakita and Hiroyuki Suzuki and Takaya Handa and Youngna Kang and Yuki Ariyasu and Tatsuo Tsukamoto and Shuichiro Endo and Hitomi Miyata and Hiroyuki Yamada and Toshiko Ito-Ihara and Shunya Uchida and Hajime Kono and Yoshihide Fujigaki and Hirotoshi Kikuchi and Toshihiro Nanki and Hideki Kato and Akiko Okamoto and Kurumi Asako and Kazuo Suzuki and Yoshitomo Hamano and Kunihiro Yamagata and Joichi Usui and Shouichi Fujimoto and Yuji Sato and Masao Kikuchi and S{\'a}nchez-Guerrero, {Sergio A.} and Michael Collins and John Schollum and {de Zoysa}, Janak and Vicki Quincy and Peter Sizeland and Knut Aasarod and Marit Solbu and Bruun, {Trude Jannecke} and Wenche Koldingsnes and Anna Wludarczyk and Ilona Nowak and Jacek Gorka and Jan Sznajd and Agnieszka Padjas and Milosz Jankowski and Agnieszka Widawska and Wojciech Szczeklik and Jose Ballarin and Annette Bruchfeld and Tingting Li and Richard Brasington",

note = "Publisher Copyright: Copyright {\textcopyright} 2024 by the American Thoracic Society.",

year = "2024",

month = may,

day = "1",

doi = "10.1164/rccm.202308-1426OC",

language = "English",

volume = "209",

pages = "1141--1151",

journal = "American journal of respiratory and critical care medicine",

issn = "1073-449X",

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the PEXIVAS Investigators, Fussner, LA, Flores-Suárez, LF, Cartin-Ceba, R, Specks, U, Cox, PG, Jayne, DRW, Merkel, PA, Walsh, M, Paizis, K, Walters, G, Jardine, M, Milton, C, Ibraham, A, Siva, B, Desmond, M, Perkovic, V, Kurtkoti, J, Vilayur, E, Cass, A, Summers, S, Brown, F, Ryan, J, Kerr, P, Noble, E, Luxton, G, Mudge, DW, Hawley, C, Johnson, DW, Peh, CA, Faull, RJ, Ranganathan, D, Jeffs, L, Nicholls, K, Hughes, P, Cooper, B, Boudville, N, Ford, S, Langham, R, Reidlinger, D, Morrish, A, Badve, SV, Pascoe, E, Paul-Brent, PA, Robison, L, Valks, A, Blockmans, D, Henckaerts, L, Sprangers, B, Suri, R, Brachemi, S, Clark, W, Garg, A, Carette, S, Pagnoux, C, Reich, H, Barth, D, Khalidi, N, Cox, G, Mazzetti, A, Robins, D, Wald, R, Perl, J, Pavenski, K, Dacouris, N, Levin, A, Copland, M, Fairhead, T, Pannu, N, Qarni, MU, Habib, S, Girard, L, Manns, B, Tesar, V, Hruskova, Z, Chocova, Z, Povlsen, J, Gregersen, J, Ivarsen, P, Birn, H, Krarup, E, Pedersen, EB, Thomsen, I, Bech, JN, Szpirt, W, Egfjord, M, Mesbah, R, Bataille, P, Rey, I, Chantrel, F, Vanhille, P, Quémeneur, T, Carron, PL, Zaoui, P, de Moreuil, C, Gosselin, M, Delluc, A, Hanrotel-Saliou, C, Le Jeune, M, Ficheux, M, Aniort, J, Lavigne, C, Augusto, JF, Chauveau, D, Guitard, J, Huart, A, Ribes, D, Gatault, P, Becmeur, C, Muller, S, Betz, V, Klein, A, Blaison, G, Seror, R, Francois, H, Mariette, X, Aubrun, A, Coustet, B, Palazzo, E, Ottaviani, S, Goulenok, T, Daugas, E, Dieudé, P, Papo, T, Lebas, C, Lionet, A, Guillevin, L, Mouthon, L, Puéchal, X, Jourde-Chiche, N, Ruivard, M, Karras, A, Limal, N, Kofman, T, Le Quellec, A, Maurier, F, Gibelin, A, Parrot, A, Bachmeyer, C, Gombert, B, Nouvier, M, Lega, JC, Fain, O, Andrès, E, Cottet, R, Gregorini, G, Jeannin, G, Possenti, S, Buzio, C, Vaglio, A, Oliva, E, Makino, H, Muso, E, Endo, T, Kakita, H, Suzuki, H, Handa, T, Kang, Y, Ariyasu, Y, Tsukamoto, T, Endo, S, Miyata, H, Yamada, H, Ito-Ihara, T, Uchida, S, Kono, H, Fujigaki, Y, Kikuchi, H, Nanki, T, Kato, H, Okamoto, A, Asako, K, Suzuki, K, Hamano, Y, Yamagata, K, Usui, J, Fujimoto, S, Sato, Y, Kikuchi, M, Sánchez-Guerrero, SA, Collins, M, Schollum, J, de Zoysa, J, Quincy, V, Sizeland, P, Aasarod, K, Solbu, M, Bruun, TJ, Koldingsnes, W, Wludarczyk, A, Nowak, I, Gorka, J, Sznajd, J, Padjas, A, Jankowski, M, Widawska, A, Szczeklik, W, Ballarin, J, Bruchfeld, A, Li, T & Brasington, R 2024, 'Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Results of an International Randomized Controlled Trial (PEXIVAS)', American journal of respiratory and critical care medicine, vol. 209, no. 9, pp. 1141-1151. https://doi.org/10.1164/rccm.202308-1426OC

Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Results of an International Randomized Controlled Trial (PEXIVAS). / the PEXIVAS Investigators; Fussner, Lynn A.; Flores-Suárez, Luis Felipe et al.
In: American journal of respiratory and critical care medicine, Vol. 209, No. 9, 01.05.2024, p. 1141-1151.

Research output: Contribution to journal › Article › peer-review

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 - Li, Tingting

AU - Brasington, Richard

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 -

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

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