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

• Published in: Kidney international Vol. 95; no. 1; pp. 219 - 231
• Main Authors: 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, Loaeza, Arturo Reyes, Gutierrez Urena, Sergio Ramon, 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, 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, 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., 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, 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019
• Subjects: Adult; calcineurin inhibitors; Calcineurin Inhibitors - administration & dosage; Calcineurin Inhibitors - adverse effects; Cyclosporine - administration & dosage; Cyclosporine - adverse effects; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination - adverse effects; Drug Therapy, Combination - methods; Female; glomerulonephritis; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; kidney biopsy; Lupus Nephritis - drug therapy; Lupus Nephritis - mortality; Male; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - adverse effects; proteinuria; Remission Induction - methods; systemic lupus erythematosus; Treatment Outcome; Young Adult; systemic lupus erythematosus; kidney biopsy; glomerulonephritis; proteinuria; calcineurin inhibitors
• ISSN: 0085-2538; 1523-1755; 1523-1755
• DOI: 10.1016/j.kint.2018.08.025

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. [Display omitted]