REGENERATE showed that treatment with OCA improved histological liver fibrosis in NASH patients.1 However, liver biopsy is an impractical tool to monitor patients’ response to therapy. Here, we evaluate the potential utility of non-invasive tests in monitoring NASH patients with fibrosis during treatment. Patients with fibrosis stages 2 and 3 were randomized (1:1:1) to placebo, OCA 10mg or OCA 25mg QD. Change in non-invasive biomarker scores of fibrosis (FIB-4 index, AST to platelet ratio index [APRI]), FibroSure® and NASH (CK-18), and liver stiffness via transient elastography (TE, subset of patients), were assessed. At baseline, average biomarker scores and liver stiffness were similar across treatment groups (ITT; placebo n = 311, OCA 10mg n = 312, OCA 25mg n = 308; 56% F3). OCA treated patients showed improvement across several measures captured in Regenerate as early as six months after treatment initiation: fibrosis scores (APRI and FIB-4), markers of fibrosis (FibroSure), and markers of definite NASH (CK-18) (table). Improvements were generally dose-dependent and maintained over the duration of 18 months. TE, a surrogate marker for liver fibrosis, decreased from baseline in both OCA groups but increased with placebo at 18 months. Improvements in TE were dose and time dependent and were observed in both F2 and F3 patients; a greater dose-dependent response was observed in F3 patients. Treatment with OCA resulted in early and consistent improvements across several non-invasive measures of fibrosis and NASH, suggesting serum tests are useful for monitoring early treatment response. Liver stiffness as assessed by TE also improved, with a dose-dependent reduction by month 18, consistent with histologic improvement seen in REGENERATE. 1 Interim analysis results at 18 months are based on surrogate endpoints and impact on clinical outcomes has not been confirmed. The REGENERATE study is ongoing to confirm the clinical benefit of OCA.
Obeticholic acid (OCA) improves non-invasive markers of fibrosis in patients with non-alcoholic steatohepatitis (NASH): a secondary analysis of the phase 3 Regenerate study
Bugianesi E;
2020-01-01
Abstract
REGENERATE showed that treatment with OCA improved histological liver fibrosis in NASH patients.1 However, liver biopsy is an impractical tool to monitor patients’ response to therapy. Here, we evaluate the potential utility of non-invasive tests in monitoring NASH patients with fibrosis during treatment. Patients with fibrosis stages 2 and 3 were randomized (1:1:1) to placebo, OCA 10mg or OCA 25mg QD. Change in non-invasive biomarker scores of fibrosis (FIB-4 index, AST to platelet ratio index [APRI]), FibroSure® and NASH (CK-18), and liver stiffness via transient elastography (TE, subset of patients), were assessed. At baseline, average biomarker scores and liver stiffness were similar across treatment groups (ITT; placebo n = 311, OCA 10mg n = 312, OCA 25mg n = 308; 56% F3). OCA treated patients showed improvement across several measures captured in Regenerate as early as six months after treatment initiation: fibrosis scores (APRI and FIB-4), markers of fibrosis (FibroSure), and markers of definite NASH (CK-18) (table). Improvements were generally dose-dependent and maintained over the duration of 18 months. TE, a surrogate marker for liver fibrosis, decreased from baseline in both OCA groups but increased with placebo at 18 months. Improvements in TE were dose and time dependent and were observed in both F2 and F3 patients; a greater dose-dependent response was observed in F3 patients. Treatment with OCA resulted in early and consistent improvements across several non-invasive measures of fibrosis and NASH, suggesting serum tests are useful for monitoring early treatment response. Liver stiffness as assessed by TE also improved, with a dose-dependent reduction by month 18, consistent with histologic improvement seen in REGENERATE. 1 Interim analysis results at 18 months are based on surrogate endpoints and impact on clinical outcomes has not been confirmed. The REGENERATE study is ongoing to confirm the clinical benefit of OCA.
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