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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)219-231
Number of pages13
JournalKidney International
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

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{13afc565449a4039a71849c7a892dcc0,
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",
number = "1",

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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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DO - 10.1016/j.kint.2018.08.025

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JO - Kidney International

JF - Kidney International

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