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

AURA-LV Study Group, Brad H. Rovin, Neil Solomons, William F. Pendergraft, Mary Anne Dooley, James Tumlin, Juanita Romero-Diaz, Lidia Lysenko, Sandra V. Navarra, Robert B. Huizinga, Ihar Adzerikho, Elena Mikhailova, Natalya Mitkovskaya, Sergey Pimanov, Nikolay Soroka, Boris Iliev Bogov, Boriana Deliyska, Valentin Ikonomov, Eduard Tilkiyan, Ruth Almeida & 31 others Fernando Jimenez, Faud Teran, Irma Tchokhonelidze, Nino Tsiskarishvili, Maynor Herrera Mendez, Nilmo Noel Chavez Perez, Arturo Reyes Loaeza, Sergio Ramon Gutierrez Urena, Juanita Romero Diaz, Rodolfo Araiza Casillas, Magdalena Madero Rovalo, Stanislaw Niemczyk, Antoni Sokalski, Andrzej Wiecek, Marian Klinger, Olga V. Bugrova, Tatiana M. Chernykh, Tatiana R. Kameneva, Lidia V. Lysenko, Tatiana A. Raskina, Olga V. ReshEtko, Natalia N. Vezikova, Tatiana V. Kropotina, Adelya N. Maksudova, Vyacheslav Marasaev, Vladimir A. Dobronravov, Ivan Gordeev, Ashot M. EssAian, Alexey Frolov, Rosa Jelacic, Ramesh Saxena

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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.

LanguageEnglish (US)
Pages219-231
Number of pages13
JournalKidney international
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2019

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Lupus Nephritis
Double-Blind Method
Placebos
Safety
Mycophenolic Acid
Kidney
Adrenal Cortex Hormones
voclosporin
Remission Induction
Standard of Care
Therapeutics

Keywords

  • calcineurin inhibitors
  • glomerulonephritis
  • kidney biopsy
  • proteinuria
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Nephrology

Cite this

@article{aa7c15a4b1be442794e6ba0a1ddf064d,
title = "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",
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.",
keywords = "calcineurin inhibitors, glomerulonephritis, kidney biopsy, proteinuria, systemic lupus erythematosus",
author = "{AURA-LV Study Group} and Rovin, {Brad H.} and Neil Solomons and Pendergraft, {William F.} and Dooley, {Mary Anne} and James Tumlin and Juanita Romero-Diaz and Lidia Lysenko and Navarra, {Sandra V.} and Huizinga, {Robert B.} and Ihar Adzerikho and Elena Mikhailova and Natalya Mitkovskaya and Sergey Pimanov and Nikolay Soroka and Bogov, {Boris Iliev} and Boriana Deliyska and Valentin Ikonomov and Eduard Tilkiyan and Ruth Almeida and Fernando Jimenez and Faud Teran and Irma Tchokhonelidze and Nino Tsiskarishvili and {Herrera Mendez}, Maynor and {Chavez Perez}, {Nilmo Noel} and Loaeza, {Arturo Reyes} and {Gutierrez Urena}, {Sergio Ramon} and {Romero Diaz}, Juanita and {Araiza Casillas}, Rodolfo and {Madero Rovalo}, Magdalena and Stanislaw Niemczyk and Antoni Sokalski and Andrzej Wiecek and Marian Klinger and Bugrova, {Olga V.} and Chernykh, {Tatiana M.} and Kameneva, {Tatiana R.} and Lysenko, {Lidia V.} and Raskina, {Tatiana A.} and ReshEtko, {Olga V.} and Vezikova, {Natalia N.} and Kropotina, {Tatiana V.} and Maksudova, {Adelya N.} and Vyacheslav Marasaev and Dobronravov, {Vladimir A.} and Ivan Gordeev and EssAian, {Ashot M.} and Alexey Frolov and Rosa Jelacic and Ramesh Saxena",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.kint.2018.08.025",
language = "English (US)",
volume = "95",
pages = "219--231",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
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TY - JOUR

T1 - 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

AU - AURA-LV Study Group

AU - Rovin, Brad H.

AU - Solomons, Neil

AU - Pendergraft, William F.

AU - Dooley, Mary Anne

AU - Tumlin, James

AU - Romero-Diaz, Juanita

AU - Lysenko, Lidia

AU - Navarra, Sandra V.

AU - Huizinga, Robert B.

AU - Adzerikho, Ihar

AU - Mikhailova, Elena

AU - Mitkovskaya, Natalya

AU - Pimanov, Sergey

AU - Soroka, Nikolay

AU - Bogov, Boris Iliev

AU - Deliyska, Boriana

AU - Ikonomov, Valentin

AU - Tilkiyan, Eduard

AU - Almeida, Ruth

AU - Jimenez, Fernando

AU - Teran, Faud

AU - Tchokhonelidze, Irma

AU - Tsiskarishvili, Nino

AU - Herrera Mendez, Maynor

AU - Chavez Perez, Nilmo Noel

AU - Loaeza, Arturo Reyes

AU - Gutierrez Urena, Sergio Ramon

AU - Romero Diaz, Juanita

AU - Araiza Casillas, Rodolfo

AU - Madero Rovalo, Magdalena

AU - Niemczyk, Stanislaw

AU - Sokalski, Antoni

AU - Wiecek, Andrzej

AU - Klinger, Marian

AU - Bugrova, Olga V.

AU - Chernykh, Tatiana M.

AU - Kameneva, Tatiana R.

AU - Lysenko, Lidia V.

AU - Raskina, Tatiana A.

AU - ReshEtko, Olga V.

AU - Vezikova, Natalia N.

AU - Kropotina, Tatiana V.

AU - Maksudova, Adelya N.

AU - Marasaev, Vyacheslav

AU - Dobronravov, Vladimir A.

AU - Gordeev, Ivan

AU - EssAian, Ashot M.

AU - Frolov, Alexey

AU - Jelacic, Rosa

AU - Saxena, Ramesh

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - calcineurin inhibitors

KW - glomerulonephritis

KW - kidney biopsy

KW - proteinuria

KW - systemic lupus erythematosus

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