Effects of Bardoxolone Methyl in Alport Syndrome
Por:
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
Publicada:
1 dic 2022
Resumen:
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.
Filiaciones:
Warady, BA:
Childrens Mercy Kansas City, Dept Pediat, Div Nephrol, Kansas City, MO 64108 USA
Pergola, PE:
Renal Associates, San Antonio, TX USA
Agarwal, R:
Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA
Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN USA
Andreoli, S:
Indiana Univ, Sch Med, Riley Hosp Children, Indianapolis, IN USA
Appel, GB:
Columbia Univ, Coll Phys & Surg, Dept Med, Div Nephrol, New York, NY USA
Bangalore, S:
New York Univ, Sch Med, Cardiovasc Clin Res Ctr, New York, NY USA
Block, GA:
US Renal Care Inc, Dept Clin Res & Med Affairs, Plano, TX USA
Chapman, AB:
Univ Chicago, Sect Nephrol, Chicago, IL USA
Chin, MP:
Reata Pharmaceut, Nephrol Dept, Inherited Kidney Disorders, Fundacio Puigvert,Inst Invest Carlos III,REDINREN,, Plano, TX USA
Gibson, KL:
Univ N Carolina, Kidney Ctr Chapel Hill, Dept Med, Div Nephrol, Chapel Hill, NC USA
Goldsberry, A:
Reata Pharmaceut, Nephrol Dept, Inherited Kidney Disorders, Fundacio Puigvert,Inst Invest Carlos III,REDINREN,, Plano, TX USA
Iijima, K:
Kobe Univ, Grad Sch Med, Dept Pediat, Kobe, Japan
Inker, LA:
Tufts Med Ctr, Div Nephrol, Boston, MA USA
Kashtan, CE:
Univ Minnesota, Med Sch, Div Pediat Nephrol, Dept Pediat Alport Syndrome Treatments & Outcomes, Minneapolis, MN USA
Masonic Childrens Hosp, Minneapolis, MN USA
Knebelmann, B:
Univ Paris Cit, Assistance Publ Hpitaux Paris, Necker Hosp, Dept Nephrol, Paris, France
Mariani, LH:
Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI USA
Meyer, CJ:
Reata Pharmaceut, Nephrol Dept, Inherited Kidney Disorders, Fundacio Puigvert,Inst Invest Carlos III,REDINREN,, Plano, TX USA
Nozu, K:
Kobe Univ, Grad Sch Med, Dept Pediat, Kobe, Japan
O'Grady, M:
Reata Pharmaceut, Nephrol Dept, Inherited Kidney Disorders, Fundacio Puigvert,Inst Invest Carlos III,REDINREN,, Plano, TX USA
Rheault, MN:
Univ Minnesota, Med Sch, Div Pediat Nephrol, Dept Pediat Alport Syndrome Treatments & Outcomes, Minneapolis, MN USA
Masonic Childrens Hosp, Minneapolis, MN USA
Silva, AL:
Boise Kidney & Hypertens Inst, Meridian, ID USA
Stenvinkel, P:
Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med, Stockholm, Sweden
Bronze
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