Effects of Bardoxolone Methyl in Alport Syndrome

Background and objectives Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome. Design, setting, participants, & measurements We randomly assigned patients...

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Autores: Warady, BA, Pergola, PE, Agarwal, R, Andreoli, S, Appel, GB, Bangalore, S, Block, GA, Chapman, AB, Chin, MP, Gibson, KL, Goldsberry, A, Iijima, K, Inker, LA, Kashtan, CE, Knebelmann, B, Mariani, LH, Meyer, CJ, Nozu, K, O'Grady, M, Rheault, MN, Silva, AL, Stenvinkel, P, Torra, R, Chertow, GM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p15309
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15309
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143513996&doi=10.2215%2fCJN.02400222&partnerID=40&md5=154deea215997cc12863379972ce3f5e
Access Level:acceso abierto
Palabra clave:Alport syndrome
bardoxolone methyl
CKD
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spelling Effects of Bardoxolone Methyl in Alport SyndromeWarady, BAPergola, PEAgarwal, RAndreoli, SAppel, GBBangalore, SBlock, GAChapman, ABChin, MPGibson, KLGoldsberry, AIijima, KInker, LAKashtan, CEKnebelmann, BMariani, LHMeyer, CJNozu, KO'Grady, MRheault, MNSilva, ALStenvinkel, PTorra, RChertow, GMAlport syndromebardoxolone methylCKDBackground and objectives Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome. Design, setting, participants, & measurements We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.73 m(2), to bardoxolone methyl (n=77) or placebo (n=80). Primary efficacy end points were change from baseline in eGFR at weeks 48 and 100. Key secondary efficacy end points were change from baseline in eGFR at weeks 52 and 104, after an intended 4 weeks off treatment. Safety was assessed by monitoring for adverse events and change from baseline in vital signs, 12-lead electrocardiograms, laboratory measurements (including, but not limited to, aminotransferases, urinary albumin-creatinine ratio, magnesium, and B-type natriuretic peptide), and body weight. Results Patients randomized to bardoxolone methyl experienced preservation in eGFR relative to placebo at 48 and 100 weeks (between-group differences: 9.2 [97.5% confidence interval, 5.1 to 13.4; P < 0.001] and 7.4 [95% confidence interval, 3.1 to 11.7; P=0.0008] ml/min per 1.73 m(2), respectively). After a 4-week off treatment period, corresponding mean differences in eGFR were 5.4 (97.5% confidence interval, 1.8 to 9.1; P < 0.001) and 4.4 (95% confidence interval, 0.7 to 8.1; P=0.02) ml/min per 1.73 m(2) at 52 and 104 weeks, respectively. In a post hoc analysis with no imputation of missing eGFR data, the difference at week 104 was not statistically significant (1.5 [95% confidence interval, -1.9 to 4.9] ml/min per 1.73 m(2)). Discontinuations from treatment were more frequent among patients randomized to bardoxolone methyl; most discontinuations were due to protocol-specified criteria being met for increases in serum transaminases. Serious adverse events were more frequent among patients randomized to placebo. Three patients in each group developed kidney failure. Conclusions In adolescent and adult patients with Alport syndrome receiving standard of care, treatment with bardoxolone methyl resulted in preservation in eGFR relative to placebo after a 2-year study period; off-treatment results using all available data were not significantly different.AMER SOC NEPHROLOGY2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15309https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143513996&doi=10.2215%2fCJN.02400222&partnerID=40&md5=154deea215997cc12863379972ce3f5eClinical Journal of the American Society of NephrologyISSN: 15559041ISSNe: 1555905Xreponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p153092026-06-14T12:41:47Z
dc.title.none.fl_str_mv Effects of Bardoxolone Methyl in Alport Syndrome
title Effects of Bardoxolone Methyl in Alport Syndrome
spellingShingle Effects of Bardoxolone Methyl in Alport Syndrome
Warady, BA
Alport syndrome
bardoxolone methyl
CKD
title_short Effects of Bardoxolone Methyl in Alport Syndrome
title_full Effects of Bardoxolone Methyl in Alport Syndrome
title_fullStr Effects of Bardoxolone Methyl in Alport Syndrome
title_full_unstemmed Effects of Bardoxolone Methyl in Alport Syndrome
title_sort Effects of Bardoxolone Methyl in Alport Syndrome
dc.creator.none.fl_str_mv Warady, BA
Pergola, PE
Agarwal, R
Andreoli, S
Appel, GB
Bangalore, S
Block, GA
Chapman, AB
Chin, MP
Gibson, KL
Goldsberry, A
Iijima, K
Inker, LA
Kashtan, CE
Knebelmann, B
Mariani, LH
Meyer, CJ
Nozu, K
O'Grady, M
Rheault, MN
Silva, AL
Stenvinkel, P
Torra, R
Chertow, GM
author Warady, BA
author_facet Warady, BA
Pergola, PE
Agarwal, R
Andreoli, S
Appel, GB
Bangalore, S
Block, GA
Chapman, AB
Chin, MP
Gibson, KL
Goldsberry, A
Iijima, K
Inker, LA
Kashtan, CE
Knebelmann, B
Mariani, LH
Meyer, CJ
Nozu, K
O'Grady, M
Rheault, MN
Silva, AL
Stenvinkel, P
Torra, R
Chertow, GM
author_role author
author2 Pergola, PE
Agarwal, R
Andreoli, S
Appel, GB
Bangalore, S
Block, GA
Chapman, AB
Chin, MP
Gibson, KL
Goldsberry, A
Iijima, K
Inker, LA
Kashtan, CE
Knebelmann, B
Mariani, LH
Meyer, CJ
Nozu, K
O'Grady, M
Rheault, MN
Silva, AL
Stenvinkel, P
Torra, R
Chertow, GM
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alport syndrome
bardoxolone methyl
CKD
topic Alport syndrome
bardoxolone methyl
CKD
description Background and objectives Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome. Design, setting, participants, & measurements We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.73 m(2), to bardoxolone methyl (n=77) or placebo (n=80). Primary efficacy end points were change from baseline in eGFR at weeks 48 and 100. Key secondary efficacy end points were change from baseline in eGFR at weeks 52 and 104, after an intended 4 weeks off treatment. Safety was assessed by monitoring for adverse events and change from baseline in vital signs, 12-lead electrocardiograms, laboratory measurements (including, but not limited to, aminotransferases, urinary albumin-creatinine ratio, magnesium, and B-type natriuretic peptide), and body weight. Results Patients randomized to bardoxolone methyl experienced preservation in eGFR relative to placebo at 48 and 100 weeks (between-group differences: 9.2 [97.5% confidence interval, 5.1 to 13.4; P < 0.001] and 7.4 [95% confidence interval, 3.1 to 11.7; P=0.0008] ml/min per 1.73 m(2), respectively). After a 4-week off treatment period, corresponding mean differences in eGFR were 5.4 (97.5% confidence interval, 1.8 to 9.1; P < 0.001) and 4.4 (95% confidence interval, 0.7 to 8.1; P=0.02) ml/min per 1.73 m(2) at 52 and 104 weeks, respectively. In a post hoc analysis with no imputation of missing eGFR data, the difference at week 104 was not statistically significant (1.5 [95% confidence interval, -1.9 to 4.9] ml/min per 1.73 m(2)). Discontinuations from treatment were more frequent among patients randomized to bardoxolone methyl; most discontinuations were due to protocol-specified criteria being met for increases in serum transaminases. Serious adverse events were more frequent among patients randomized to placebo. Three patients in each group developed kidney failure. Conclusions In adolescent and adult patients with Alport syndrome receiving standard of care, treatment with bardoxolone methyl resulted in preservation in eGFR relative to placebo after a 2-year study period; off-treatment results using all available data were not significantly different.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15309
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143513996&doi=10.2215%2fCJN.02400222&partnerID=40&md5=154deea215997cc12863379972ce3f5e
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15309
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143513996&doi=10.2215%2fCJN.02400222&partnerID=40&md5=154deea215997cc12863379972ce3f5e
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv AMER SOC NEPHROLOGY
publisher.none.fl_str_mv AMER SOC NEPHROLOGY
dc.source.none.fl_str_mv Clinical Journal of the American Society of Nephrology
ISSN: 15559041
ISSNe: 1555905X
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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