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Ocaliva associated with collagen improvement in patients with PBC
SAN DIEGO – Post-hoc analysis of data from a POISE substudy has shown reduction in fibrosis “supporting the overall trend of improvement or no progression in the histologic components of PBC,” a rare autoimmune liver disease of intrahepatic bile ducts leading to progressive fibrosis and eventual cirrhosis, according to a researcher here.
“Measuring collagen content is emerging as a reliable method of quantifying liver fibrosis and has shown evidence of being an effective tool in [patients with] PBC,” said Paul Pockros, MD, speaking at Digestive Disease Week.
“Second harmonic generation (SHG) microscopy is a new tissue imaging technology that allows the accurate quantification of several collagen parameters on unstained tissue sections,” he said. “So, it is different than the morphometry we used in the past.”
In 2016, the FDA granted approval for Ocaliva (obeticholic acid, Intercept) for the second-line treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) for adults who failed therapy with UDCA alone, or as a single therapy in adults intolerable to UDCA.
“The approval was based on a surrogate endopoint of biochemistry being alkaline phosphate and bilirubin,” Pockros said.
Pockros presented a new post-hoc analysis that was planned in the phase 3 POISE study “from the beginning” that assessed the impact of 3 years of Ocaliva treatment on collagen morphometry using biopsy samples from the POISE study.
Researchers identified two cohorts – an All Biopsy Population (n=30; adequate biopsy samples with collagen data) and a Paired Biopsy Population (n=16; both a baseline sample and a follow-up biopsy with collagen data).
In the All Biopsy Population, trends were observed between increasing median Collagen Area Ratio (CAR), Collagen Fiber Density (CFD), and Collagen Reticulation Index (CRI) and Fibrosis Composite Score (FCS) using the Nakanuma fibrosis scoring system.
“You may not be familiar with [the Nakanuma scoring system] ... but it is an accepted scoring system for PBC and it uses not only fibrosis but also bile duct loss and inflammation and a few other features that are important in PBC,” Pockros said.
Pockros said the Nakanuma scoring was done by two liver pathologists with consensual readings “blinded to randomization.”
“The majority of patients with PBC who received 3 years of OCA treatment showed improvement or stabilization in collagen morphometry,” he said. “We definitely saw reduction in fibrosis.”
Pockros noted that significant reductions were observed in collagen area ratio, collagen fiber density and collagen reticulation index “and all of these were significantly significant.”
“Morphometric measures of fibrosis increased with increased with increasing histologic disease severity as assessed by the gold standard, which is the Nakanuma fibrosis score, supporting the validity of collagen measurements by this technique.”
“The data from this POISE subgroup analysis support that in patients with inadequate response to UCDA, 3 years of OCA treatment results in an improvement or stabilization in fibrosis progression,” Pockros said. – by Joan-Marie Stiglich, ELS
Reference:
Pockros P. Session 4675. Presented at: Digestive Disease Week 2019. May 18-21; San Diego, California.
Disclosure: Pockros reports ties to AbbVie, Conatus, Genfit, Gilead, Intercept, Molecular Stethoscope and Prometheus.