Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan
Frank B. Cortazar, John L. Niles, David Jayne, Peter A. Merkel, Annette Bruchfeld, Huibin Yue, Thomas J. Schall, Pirow Bekker, Chen Au Peh, Aron Chakera, Bruce A. Cooper, Jadadeesh Kurtkoti, Daman Langguth, Vicki Levidiotis, G. Luxton, Peter F. Mount, David W. Mudge, Euan Noble, R. Phoon, Dwarakanathan Ranganathan, A. Ritchie, Jessica Ryan, M. Suranyi, Alexander R. Rosenkranz, K. Lhotta, Andreas Kronbichler, Nathalie Demoulin, C. Bovy, R. Hellemans, Jean‐Michel Hougardy, Ben Sprangers, Katherine D. Wissing, Christian Pagnoux, S. Barbour, Soumeya Brachemi, S. Cournoyer, Louis Girard, Louis‐Philippe Laurin, Patrick Liang, David Philibert, Michael Walsh, Vladimı́r Tesař, R. Becvar, P. Horak, Ivan Rychlík, Wladimir Szpirt, Hans Dieperink, Jon Waarst Gregersen, Per Ivarsen, Elizabeth Krarup, Cecilie Lyngsøe, Claire Rigothier, Jean‐François Augusto, Alexandre Bélot, Dominique Chauveau, Divi Cornec, Noémie Jourde‐Chiche, M. Ficheux, Alexandre Karras, Armelle Klein, F. Maurier, Rafik Mesbah, Olivier Moranne, A. Néel, T. Quéméneur, David Saadoun, Benjamin Terrier, Philippe Zaoui, Matthias Schaier, Urs Benck, Raoul Bergner, Matthias H. Busch, Jürgen Floege, Franziska Grundmann, Hermann Haller, Marion Haubitz, B. Hellmich, Jörg Henes, Bernd Hohenstein, C. Hugo, Christof Iking‐Konert, Fabian Arndt, Torsten Kubacki, Ina Kötter, Peter Lamprecht, Tom H. Lindner, Jan Halbritter, H. Mehling, Ulf Schönermarck, Nils Venhoff, Volker Vielhauer, Oliver Witzke, István Szombati, G Szücs, Giacomo Garibotto, Federico Alberici, Enrico Brunetta, Lorenzo Dagna, Salvatore De Vita, Giacomo Emmi
Abstract
Introduction In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m 2 in the avacopan group and 4.1 ml/min per 1.73 m 2 in the prednisone group ( P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m 2 . Methods eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. Results In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m 2 . At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m 2 in the avacopan and prednisone groups, respectively ( P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group ( P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m 2 , respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. Conclusion Among patients with baseline eGFR ≤20 ml/min per 1.73 m 2 in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.