Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan

Frank B Cortazar; John L Niles; David R W Jayne; Peter A Merkel; Annette Bruchfeld; Huibin Yue; Thomas J Schall; Pirow Bekker; ADVOCATE Study Group

doi:10.1016/j.ekir.2023.01.039

Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan

Kidney Int Rep. 2023 Feb 3;8(4):860-870. doi: 10.1016/j.ekir.2023.01.039. eCollection 2023 Apr.

Authors

Frank B Cortazar¹, John L Niles², David R W Jayne³, Peter A Merkel⁴, Annette Bruchfeld^{5

6}, Huibin Yue⁶, Thomas J Schall⁶, Pirow Bekker⁶; ADVOCATE Study Group

Collaborators

ADVOCATE Study Group:
C Au Peh, A Chakera, B Cooper, J Kurtkoti, D Langguth, V Levidiotis, G Luxton, P Mount, D Mudge, E Noble, R Phoon, D Ranganathan, A Ritchie, J Ryan, M Suranyi, A Rosenkranz, K Lhotta, A Kronbichler, N Demoulin, C Bovy, R Hellemans, J Hougardy, B Sprangers, K Wissing, C Pagnoux, S Barbour, S Brachemi, S Cournoyer, L Girard, L Laurin, P Liang, D Philibert, M Walsh, V Tesar, R Becvar, P Horak, I Rychlik, W Szpirt, H Dieperink, J Gregersen, P Ivarsen, E Krarup, C Lyngsoe, C Rigothier, J Augusto, A Belot, D Chauveau, D Cornec, N Jourde-Chiche, M Ficheux, A Karras, A Klein, F Maurier, R Mesbah, O Moranne, A Neel, T Quemeneur, D Saadoun, B Terrier, P Zaoui, M Schaier, U Benck, R Bergner, M Busch, J Floege, F Grundmann, H Haller, M Haubitz, B Hellmich, J Henes, B Hohenstein, C Hugo, C Iking-Konert, F Arndt, T Kubacki, I Kotter, P Lamprecht, T Lindner, J Halbritter, H Mehling, U Schönermarck, N Venhoff, V Vielhauer, O Witzke, I Szombati, G Szucs, G Garibotto, F Alberici, E Brunetta, L Dagna, S De Vita, G Emmi, A Gabrielli, L Manenti, F Pieruzzi, D Roccatello, C Salvarani, H Dobashi, T Atsumi, S Fujimoto, N Hagino, A Ihata, S Kaname, Y Kaneko, A Katagiri, M Katayama, Y Kirino, K Kitagawa, A Komatsuda, H Kono, T Kurasawa, R Matsumura, T Mimura, A Morinobu, Y Murakawa, T Naniwa, T Nanki, N Ogawa, H Oshima, K Sada, E Sugiyama, T Takeuchi, H Taki, N Tamura, T Tsukamoto, K Yamagata, M Yamamura, P van Daele, A Rutgers, Y Teng, R Walker, I Chua, M Collins, K Rabindranath, J de Zoysa, M Svensson, B Grevbo, S Kalstad, M Little, M Clarkson, E Molloy, I Agraz Pamplona, J Anton, V Barrio Lucia, S Ciggaran, M Cinta Cid, M Diaz Encarnacion, X Fulladosa Oliveras, M Jose Soler, H Marco Rusinol, M Praga, L Quintana Porras, A Segarra, A Bruchfeld, M Segelmark, I Soveri, E Thomaidi, K Westman, T Neumann, M Burnier, T Daikeler, J Dudler, T Hauser, H Seeger, B Vogt, D Jayne, J Burton, R Al Jayyousi, T Amin, J Andrews, L Baines, P Brogan, B Dasgupta, T Doulton, O Flossmann, S Griffin, J Harper, L Harper, D Kidder, R Klocke, P Lanyon, R Luqmani, J McLaren, D Makanjuola, L McCann, A Nandagudi, S Selvan, E O'Riordan, M Patel, R Patel, C Pusey, R Rajakariar, J Robson, M Robson, A Salama, L Smyth, J Sznajd, J Taylor, P Merkel, A Sreih, E Belilos, A Bomback, J Carlin, Y Chang Chen Lin, V Derebail, S Dragoi, A Dua, L Forbess, D Geetha, P Gipson, R Gohh, G T Greenwood, S Hugenberg, R Jimenez, M Kaskas, T Kermani, A Kivitz, C Koening, C Langford, G Marder, A Mohamed, P Monach, N Neyra, G Niemer, J Niles, R Obi, C Owens, D Parks, A Podoll, B Rovin, R Sam, W Shergy, A Silva, U Specks, R Spiera, J Springer, C Striebich, A Swarup, S Thakar, A Tiliakos, Y Tsai, D Waguespack, M Chester Wasko

Affiliations

¹ New York Nephrology Vasculitis and Glomerular Center, Saint Peter's Hospital-Albany, Albany, New York, USA.
² Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
³ Department of Medicine, University of Cambridge, Cambridge, UK.
⁴ Division of Rheumatology, Department of Medicine, Division of Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵ Department of Renal Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
⁶ ChemoCentryx, Inc., San Carlos, California, USA.

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 m² in the avacopan group and 4.1 ml/min per 1.73 m² 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 m².

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 m². At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m² 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 m², 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 m² in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

Keywords: ANCA-associated vasculitis; avacopan; complement; complement 5a receptor; low eGFR; renal recovery.