Anti-TGF-ß1 Antibody Therapy in Patients with Diabetic Nephropathy.
J Am Soc Nephrol
; 28(3): 953-962, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-27647855
ABSTRACT
TGF-ß has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-ß1 activity with a TGF-ß1-specific, humanized, neutralizing monoclonal antibody (TGF-ß1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3-3.3 mg/dl for women and 1.5-3.5 mg/dl for men (or eGFR of 20-60 ml/min per 1.73 m2), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-ß1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-ß1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-ß1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Nefropatias Diabéticas
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Fator de Crescimento Transformador beta1
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Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
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Guideline
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Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Am Soc Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article