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.
Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS) / Fussner, Lynn A.; Flores-Suárez, Luis Felipe; Cartin-Ceba, Rodrigo; Specks, Ulrich; Cox, P. Gerard; Jayne, David R. W.; Merkel, Peter A.; Walsh, Michael; Paizis, Kathy; Walters, Giles; Jardine, Meg; Milton, Caroline; Ibraham, Abu; Siva, Brian; Desmond, Michael; Perkovic, Vlado; Kurtkoti, Jadadeesh; Vilayur, Eswari; Cass, Alan; Summers, Shaun; Brown, Fiona; Ryan, Jessica; Kerr, Peter; Noble, Euan; Luxton, Grant; Mudge, David W.; Hawley, Carmel; Johnson, David W.; Peh, Chen Au; Faull, Randall J.; Ranganathan, Dwarakanathan; Jeffs, Lisa; Nicholls, Kathy; Hughes, Peter; Cooper, Bruce; Boudville, Neil; Ford, Sharon; Langham, Robyn; Reidlinger, Donna; Morrish, Alicia; Badve, Sunil V.; Pascoe, Elaine; Paul-Brent, Peta-Anne; Robison, Laura; Valks, Andrea; Blockmans, Daniel; Henckaerts, Liesbet; Sprangers, Ben; Suri, Rita; Brachemi, Soumeya; Clark, William; Garg, Amit; Carette, Simon; Pagnoux, Christian; Reich, Heather; Barth, David; Walsh, Michael; Khalidi, Nader; Cox, Gerry; Mazzetti, Andrea; Robins, Diane; Wald, Ron; Perl, Jeffrey; Pavenski, Katerina; Dacouris, Niki; Levin, Adeera; Copland, Michael; Fairhead, Todd; Pannu, Neesh; Qarni, Muhammad Uwais; Habib, Syed; Girard, Louis; Manns, Braden; Tesar, Vladimir; Hruskova, Zdenka; Chocova, Zdenka; Povlsen, Johan; Gregersen, Jon; Ivarsen, Per; Birn, Henrik; Krarup, Elizabeth; Pedersen, Erling B.; Thomsen, Ingrid; Bech, Jesper Nørgaard; Szpirt, Wladmir; Egfjord, Martin; Mesbah, Rafik; Bataille, Pierre; Rey, Isabelle; Chantrel, François; Vanhille, Philipe; Quémeneur, Thomas; Carron, Pierre-Louis; Zaoui, Philippe; de Moreuil, Claire; Gosselin, Morgane; Delluc, Aurélien; Hanrotel-Saliou, Catherine; Jeune, Mathilde Le; Ficheux, Maxence; Aniort, Julien; Lavigne, Christian; Augusto, Jean Francois; Chauveau, Dominique; Guitard, Joëlle; Huart, Antoine; Ribes, David; Gatault, Philippe; Becmeur, Camille; Muller, Sandrine; Betz, Valérie; Klein, Alexandre; Blaison, Gilles; Seror, Raphaele; Francois, Hélène; Mariette, Xavier; Aubrun, Aurore; Coustet, Baptiste; Palazzo, Elisabeth; Ottaviani, Sébastien; Goulenok, Tiphaine; Daugas, Eric; Dieudé, Philipe; Papo, Thomas; Lebas, Céline; Lionet, Arnaud; Guillevin, Loïc; Mouthon, Luc; Puéchal, Xavier; Jourde-Chiche, Noémie; Ruivard, Marc; Karras, Alexandre; Limal, Nicolas; Kofman, Thomas; Quellec, Alain Le; Maurier, François; Gibelin, Aude; Parrot, Antoine; Bachmeyer, Claude; Gombert, Bruno; Nouvier, Mathilde; Lega, Jean-Christophe; Fain, Olivier; Andrès, Emmanuel; Cottet, Rachel; Gregorini, Gina; Jeannin, Guido; Possenti, Stefano; Buzio, Carlo; Vaglio, Augusto; Oliva, Elena; Makino, Hirofumi; Muso, Eri; Endo, Tomomi; Kakita, Hiroko; Suzuki, Hiroyuki; Handa, Takaya; Kang, Youngna; Ariyasu, Yuki; Tsukamoto, Tatsuo; Endo, Shuichiro; Miyata, Hitomi; Yamada, Hiroyuki; Ito-Ihara, Toshiko; Uchida, Shunya; Kono, Hajime; Fujigaki, Yoshihide; Kikuchi, Hirotoshi; Nanki, Toshihiro; Kato, Hideki; Okamoto, Akiko; Asako, Kurumi; Suzuki, Kazuo; Hamano, Yoshitomo; Yamagata, Kunihiro; Usui, Joichi; Fujimoto, Shouichi; Sato, Yuji; Kikuchi, Masao; Flores-Suárez, Luis Felipe; Sánchez-Guerrero, Sergio A.; Collins, Michael; Schollum, John; de Zoysa, Janak; Quincy, Vicki; Sizeland, Peter; Aasarod, Knut; Solbu, Marit; Bruun, Trude Jannecke; Koldingsnes, Wenche; Wludarczyk, Anna; Nowak, Ilona; Gorka, Jacek; Sznajd, Jan; Padjas, Agnieszka; Jankowski, Milosz; Widawska, Agnieszka; Szczeklik, Wojciech; Ballarin, Jose; Bruchfeld, Annette; Efvergren, Mats; Eriksson, Per; Westman, Kerstin; Selga, Daina; Heijl, Caroline; Ohlsson, Sophie; Segelmark, Marten; Basu, Neil; Kidder, Dana; Fluck, Nicholas; Jayne, David R. W.; Smith, Rona; Wilcocks, Lisa; McClure, Mark; Jones, Rachel; Trivedi, Sapna; Gopaluni, Seerapani; Brettell, Elizabeth; Crump, Paul; Feilbach, Annika; Hewitt, Catherine; Hilken, Nick; Howman, Andrew; Hughes, Terry; Ives, Natalie; Jarrett, Hugh; Mehta, Samir; Record, Rebecca; Ryan, Gemma; Sidile, Chaka; Wheatley, Keith; Sheerin, null; Brown, Alison; Baines, Laura Anne; Lordan, Jim; Pusey, Charles; Tanna, Anisha; McAdoo, Stephen; Levy, Jeremy; Griffith, Megan; Klebe, Bernhard; Doulton, Timothy; Warwick, Graham; Burton, James; Barratt, Jonathon; Topham, Peter; Baines, Richard; Brunskill, Nigel; Al-Jayyousi, Reem; Hamilton, Patrick; Patel, Mumtaz; Mitra, Sandip; Brown, Nina; Sharples, Edward; Luqmani, Raashid; Harper, Lorraine; Rhodes, Benjamin; Chanouzas, Dimitrios; Morgan, Matthew; Hewins, Peter; Floßmann, Oliver; Bhandary, Nitin; Foxton, Julie; Jones, Linda; King, Jenny; Smyth, Lucy; D'Souza, Richard; Haigh, Richard; Hough, Maxine; Salama, Alan; Burns, Aine; Little, Mark; Dhaun, Neeraj; Dhaygude, Ajay; Basnayake, Kolitha; Iggo, Neil; Jones, Daniel; Oliveira, David; MacPhee, Iain A. M.; Dunn, Emma; Lewington, Andrew J. P.; Fan, Stanley Linsun; Rajakariar, Ravindra; Yaqoob, Magdi; Short, Andrew; Geddes, Colin; Mackinnon, Bruce; Jardine, Alan G.; Monach, Paul; Merkel, Peter A.; Amudala, Naomi; Quillen, Karen; Weisman, Michael; Wallace, Daniel; Forbess, Lindsy; Venuturupalli, Swamy; Langford, Carol; Hajj-Ali, Rula; Koo, Anna; Hoffman, Gary; Specks, Ulrich; Keogh, Karina; Ytterberg, Steven; Winters, Jeff; Warrington, Kenneth; Cartin-Ceba, Rodrigo; Peikert, Tobias; Fervenza, Fernando; Baqir, Misbah; Nachman, Patrick; Detwiler, Randy; Mottl, Amy; Derebail, Vimal; McGregor, JulieAnne; Merkel, Peter A.; Sreih, Antoine; Rhee, Rennie; McAlear, Carol; Aqui, Nicole; Moreland, Larry; Kiss, Joseph; Liang, Kimberly; Mohan, Niveditha; Balogun, Rasheed; Li, Tingting; Brasington, Richard; Rees, Andrew; Scott, David; Roderick, Paul; Landray, Martin; Watts, Richard; Emberson, Jonathan. - In: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. - ISSN 1073-449X. - STAMPA. - 209:(2024), pp. 1141-1151. [10.1164/rccm.202308-1426oc]
Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS)
Vaglio, Augusto;
2024
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.
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