학술논문
A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis
Document Type
Article
Author
Rovin, Brad H.; Solomons, Neil; Pendergraft, William F.; Dooley, Mary Anne; Tumlin, James; Romero-Diaz, Juanita; Lysenko, Lidia; Navarra, Sandra V.; Huizinga, Robert B.; Adzerikho, Ihar; Mikhailova, Elena; Mitkovskaya, Natalya; Pimanov, Sergey; Soroka, Nikolay; Bogov, Boris Iliev; Deliyska, Boriana; Ikonomov, Valentin; Tilkiyan, Eduard; Almeida, Ruth; Jimenez, Fernando; Teran, Faud; Tchokhonelidze, Irma; Tsiskarishvili, Nino; Herrera Mendez, Maynor; Chavez Perez, Nilmo Noel; Loaeza, Arturo Reyes; Gutierrez Urena, Sergio Ramon; Romero Diaz, Juanita; Araiza Casillas, Rodolfo; Madero Rovalo, Magdalena; Niemczyk, Stanislaw; Sokalski, Antoni; Wiecek, Andrzej; Klinger, Marian; Bugrova, Olga V.; Chernykh, Tatiana M.; Kameneva, Tatiana R.; Lysenko, Lidia V.; Raskina, Tatiana A.; ReshEtko, Olga V.; Vezikova, Natalia N.; Kropotina, Tatiana V.; Maksudova, Adelya N.; Marasaev, Vyacheslav; Dobronravov, Vladimir A.; Gordeev, Ivan; EssAian, Ashot M.; Frolov, Alexey; Jelacic, Rosa; Jovanovic, Dragan; Mitic, Branka; Pekovic, Gordana; Radovic, Milan; Radunovic, Goran; Carreira, Patricia; Diaz Gonzalez, Federico; Fulladosa, Xavier; Ucar, Eduardo; De Silva, Shamila; Herath, Chula; Hewageegana, Anura; Nazar, Abdul Latiff Mohamed; Wazil, A.W.M.; Dudar, Iryna; Godlevska, Olga; Korneyeva, Svitlana; Vasylets, ViktoriIa; Sydor, Nataliya; Kolesnyk, Mykola; Parikh, Samir V.; Olsen, Nancy; Ginzler, Ellen M.; Tumlin, James A.; Saxena, Amit; Saxena, Ramesh; Lafayette, Richard Alan; Pendergraft, William Franklin; Podoll, Amber S.; Arrey-Mensah, Annie A.; Bubb, Michael; Grossman, Jennifer; Oporta, Alejandro I.; Nami, Alireza; Rahman, Md. Mujibur; Haq, Syed Atiqul; Chan, Tak Mao Daniel; Temy, Mok Mo Yin; Gomez, Harold Michael P.; Bermas, James; Reyes, Bernadette Heizel; Hao, Llewellyn T.; Roberto, Linda Charmaine; Amante, Eric; Navarra, Sandra V.; Lanzon, Allan E.; Choe, Jung-Yoon; Kang, Tae Young; Kim, Yon Su; Lee, Seung-Geun; Lee, Ji Soo; Jun, Jason Choo Chon; Vasudevan, Archana; Luo, Shue-Fen; Cheng, Tien-Tsai; Satirapoj, Bancha; Noppakun, Kajohnsak
Source
Kidney International; January 2019, Vol. 95 Issue: 1 p219-231, 13p
Subject
Language
ISSN
00852538; 15231755
Abstract
Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.