Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS)
Authors: 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, Michael Walsh, 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, Hélène Francois, Xavier Mariette, Aurore Aubrun, Baptiste Coustet, Elisabeth Palazzo, Sébastien Ottaviani, Tiphaine Goulenok, Eric Daugas, Philipe Dieudé, Thomas Papo, Céline Lebas, Arnaud Lionet, Loïc 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, Luis Felipe Flores-Suárez, 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, Mats Efvergren, Per Eriksson, Kerstin Westman, Daina Selga, Caroline Heijl, Sophie Ohlsson, Marten Segelmark, Neil Basu, Dana Kidder, Nicholas Fluck, David R. W. Jayne, Rona Smith, Lisa Wilcocks, Mark McClure, Rachel Jones, Sapna Trivedi, Seerapani Gopaluni, Elizabeth Brettell, Paul Crump, Annika Feilbach, Catherine Hewitt, Nick Hilken, Andrew Howman, Terry Hughes, Natalie Ives, Hugh Jarrett, Samir Mehta, Rebecca Record, Gemma Ryan, Chaka Sidile, Keith Wheatley, None Sheerin, Alison Brown, Laura Anne Baines, Jim Lordan, Charles Pusey, Anisha Tanna, Stephen McAdoo, Jeremy Levy, Megan Griffith, Bernhard Klebe, Timothy Doulton, Graham Warwick, James Burton, Jonathon Barratt, Peter Topham, Richard Baines, Nigel Brunskill, Reem Al-Jayyousi, Patrick Hamilton, Mumtaz Patel, Sandip Mitra, Nina Brown, Edward Sharples, Raashid Luqmani, Lorraine Harper, Benjamin Rhodes, Dimitrios Chanouzas, Matthew Morgan, Peter Hewins, Oliver Floßmann, Nitin Bhandary, Julie Foxton, Linda Jones, Jenny King, Lucy Smyth, Richard D’Souza, Richard Haigh, Maxine Hough, Alan Salama, Aine Burns, Mark Little, Neeraj Dhaun, Ajay Dhaygude, Kolitha Basnayake, Neil Iggo, Daniel Jones, David Oliveira, Iain A. M. MacPhee, Emma Dunn, Andrew J. P. Lewington, Stanley Linsun Fan, Ravindra Rajakariar, Magdi Yaqoob, Andrew Short, Colin Geddes, Bruce Mackinnon, Alan G. Jardine, Paul Monach, Peter A. Merkel, Naomi Amudala, Karen Quillen, Michael Weisman, Daniel Wallace, Lindsy Forbess, Swamy Venuturupalli, Carol Langford, Rula Hajj-Ali, Anna Koo, Gary Hoffman, Ulrich Specks, Karina Keogh, Steven Ytterberg, Jeff Winters, Kenneth Warrington, Rodrigo Cartin-Ceba, Tobias Peikert, Fernando Fervenza, Misbah Baqir, Patrick Nachman, Randy Detwiler, Amy Mottl, Vimal Derebail, JulieAnne McGregor, Peter A. Merkel, Antoine Sreih, Rennie Rhee, Carol McAlear, Nicole Aqui, Larry Moreland, Joseph Kiss, Kimberly Liang, Niveditha Mohan, Rasheed Balogun, Tingting Li, Richard Brasington, Andrew Rees, David Scott, Paul Roderick, Martin Landray, Richard Watts, Jonathan Emberson
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The Plasma Exchange (PLEX) and Glucocorticoids (GC) in Severe AAV (PEXIVAS;NCT00987389) trial was the largest in AAV and first to enroll participants with DAH requiring mechanical ventilation. Objectives: Evaluate characteristics, treatment effects, outcomes for patients with AAV with and without DAH. Methods: PEXIVAS randomized 704 participants to PLEX or no-PLEX and reduced or standard-dose GC. DAH status was defined at enrollment as no-DAH, non-severe, or severe (room air SpO2≤85% 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-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 one year vs. 15/96(15.6%) with no-PLEX (HR 0.52,CI 0.21-1.24), while 13/96(13.5%) receiving reduced-GC died vs. 10/95(10.5%) with standard-GC (HR 1.33,CI 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX vs. no-PLEX (medians 25,IQR 22-26 vs. 22-27), fewer with reduced-GC (23[20-25]) vs. standard-GC (26[25-28]). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191(12.0%) with DAH died within one year vs. 34/513(6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Conclusion: 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. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT00987389.