Long-term obeticholic acid treatment leads to reversal or stabilization of fibrosis/cirrhosis in patients with PBC

April 13, 2018, European Association for the Study of the Liver

The first results from the POISE biopsy sub-study have today confirmed that long-term treatment with obeticholic acid (OCA) leads to the reversal or stabilization of fibrosis/cirrhosis in patients with primary biliary cholangitis (PBC) who have had an incomplete response to ursodeoxycholic acid (UDCA). These results provide the first evidence that improvements in biochemical markers of PBC observed in previous studies are accompanied by anti-fibrotic effects in line with those observed in pre-clinical trials.

"There is strong evidence from clinical trials that OCA leads to significant reductions in alkaline phosphatase (ALP) that are predicted to improve clinical outcomes of patients with PBC who do not respond adequately to or do not tolerate UDCA," said Dr. Christopher Bowlus from the University of California, Davis in the USA, who presented the results today at The International Liver Congress 2018 in Paris, France. "This study offers the first evidence from paired that OCA is indeed a disease-modifying therapy."

Primary biliary cholangitis is a rare characterized by biliary destruction, progressive cholestasis, and, ultimately, the development of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC).The primary medical treatment for PBC is UDCA, however, up to 40% of patients have an insufficient response to this treatment, putting them at risk of potentially life-threatening complications.

Obeticholic acid is a potent agonist of the farnesoid X receptor (FXR), which regulates bile acid synthesis and transport. Two previously reported Phase 2 studies and a pivotal Phase 3 study (POISE)6 confirmed that OCA, primarily in combination with UDCA, leads to significant reductions in serum ALP and improvements in other biochemical liver markers, leading to the recent approval of the treatment by the US Food and Drug Administration (FDA).

The biopsy sub-study of POISE involved patients undergoing liver biopsies prior to, and after 3 years of, treatment with OCA. Biopsies were centrally read and assessed using a six-tier staging system (from no fibrosis to cirrhosis). Thirteen patients—all receiving treatment with UDCA at baseline—had paired biopsies that were adequate for analysis.

At baseline, nine of the 13 patients (69%) presented with pre-cirrhotic fibrosis and four (31%) with cirrhosis. At the last visit before the final biopsy, serum ALP was reduced and direct bilirubin levels were comparable to baseline (median changes from baseline: -99 U/L and 0.0 μmol/L, respectively). After 3 years of OCA treatment, the majority of patients improved (n=6; 46%) or maintained (n=5; 38%) their histological stage, while two patients (15%) deteriorated. Of the four patients with baseline cirrhosis, three (75%) improved to fibrosis without cirrhosis while receiving OCA treatment.

"Eighty-five percent of the patients with PBC in this study with an incomplete response to UDCA had regression or no worsening of their fibrosis or cirrhosis after 3 years of OCA treatment—a period of time during which we would have expected some degree of fibrosis progression," said Dr. Bowlus. "OCA represents the first new treatment approved for PBC in decades, and these results support the potential of OCA to slow disease progression in this group of patients who have the greatest need for new treatments. The results of the ongoing COBALT study will determine if the biochemical improvements of the POISE study and the histological results reported here translate to improved clinical outcomes' (NCT02308111).

"Relevant changes are on the way for the management of with PBC, for which ursodeoxycholic acid has been the only option for a long time," said Prof. Marco Marzioni from the University Hospital of Ancona, Italy, and EASL Governing Board Member. "Now new medicines are coming and the first of these to be available, , has been shown to ameliorate surrogate markers of disease progression. The current study, however, reports the first evidence that OCA is also able to halt the deposition of collagen tissue in the liver, a significant outcome for the natural history of PBC."

Explore further: Phase 2 studies of two novel treatments for primary biliary cholangitis report encouraging results

Related Stories

Phase 2 studies of two novel treatments for primary biliary cholangitis report encouraging results

April 13, 2018
Preliminary results from two ongoing Phase 2 studies of novel agents under investigation for the treatment of primary biliary cholangitis (PBC) have suggested promising efficacy, safety and tolerability profiles in patients ...

Statins associated with reduced morbidity and mortality in patients with primary sclerosing cholangitis

April 12, 2018
A large register-based study conducted in Sweden has found that statins are associated with a markedly reduced risk of all-cause mortality, liver transplantation, liver cancer, and variceal bleeding in patients with primary ...

NGM282—an engineered analogue of FGF19—shows promise in patients with primary sclerosing cholangitis

April 13, 2018
The fibroblast growth factor 19 (FGF19) engineered analogue, NGM282, inhibits bile acid synthesis, decreases markers of hepatic inflammation, and significantly improves markers of fibrosis in patients with primary sclerosing ...

Trial of fibrate therapy in primary biliary cholangitis shows treatment is well tolerated

April 22, 2017
The results of the BEZURSO study, presented today, found that bezafibrate in combination with UDCA normalised prognostic markers of liver disease in patients with primary biliary cholangitis (PBC) with an inadequate response ...

Obeticholic acid produces meaningful biochemical and clinical improvements in PBC cirrhosis patients

April 12, 2014
Results from an international Phase III study presented today at the International Liver CongressTM 2014 have shown obeticholic acid (OCA) given to patients suffering from Primary Biliary Cirrhosis (PBC) who previously had ...

FDA approves ocaliva for primary biliary cholangitis

June 1, 2016
(HealthDay)—Ocaliva (obeticholic acid) has been approved by the U.S. Food and Drug Administration to treat primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with inadequate response ...

Recommended for you

Deadly Rift Valley fever: New insight, and hope for the future

July 19, 2018
Health control measures alone could be ineffective in the long term fight against the deadly Rift Valley fever which affects both humans and animals, a new study in the journal PNAS reports.

New guidelines to diagnose, manage rare endocrine disorders

July 19, 2018
International guidelines have been published for the first time to help doctors around the globe diagnose and manage patients with a very rare set of endocrine diseases known as pseudohypoparathyroidism and its related disorders, ...

Overuse of antibiotics not what the doctor ordered

July 19, 2018
With increased use of antibiotics worldwide linked to growing antibiotic resistance, a world-first study co-authored by a QUT researcher has highlighted the growing impact of non-prescription supply of antibiotics in community ...

Alcohol-related cirrhosis deaths skyrocket in young adults

July 18, 2018
Deaths from cirrhosis rose in all but one state between 1999-2016, with increases seen most often among young adults, a new study shows.

Hidden blood in feces may signal deadly conditions

July 17, 2018
(HealthDay)—Even if it's not visible to the naked eye, blood in the stool can be serious—a sign of a potentially fatal disease other than colon cancer, new research suggests.

Childhood abuse linked to greater risk of endometriosis, study finds

July 17, 2018
Endometriosis, a painful condition that affects one in 10 reproductive-age women in the U.S., has been linked to childhood physical and sexual abuse, according to findings published today in the journal Human Reproduction.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.