BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, −3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.)
Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis / Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, Hawley CM, Khalidi N, Floßmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suárez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW; PEXIVAS Investigators, Kathy Paizis, Giles Walters, Meg Jardine, Caroline Milton, Abu Ibraham, Brian Silva, 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, Loïc Guillevin, Luc Mouthon, Noémie Jourde-Chiche, Clermont-Ferrand Clermont-Ferrand, 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, Neil S 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, Sandeep 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, Antoine Sreih, Rennie Rhee, Carol McAlear, Nicole Aqui, Larry Moreland, Joseph Kiss, Kimberly Liang, Niveditha Mohan, Rasheed Balogun, Tingting Li, Richard Brasington, David R W Jayne, Andrew Rees, David Scott, Paul Roderick, Martin Landray, Richard Watts, Jonathan Emberson. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - ELETTRONICO. - 382:(2020), pp. 622-631. [10.1056/NEJMoa1803537]
Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis
Augusto VaglioMembro del Collaboration Group
;
2020
Abstract
BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, −3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.)
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