Real-world experience with obeticholic acid in patients with primary biliary cholangitis
Open accessAbstract
Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria ; the secondary endpoint was the biochemical response according to normal range criteria , defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria , and 11% by normal range criteria . Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Lay summary Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.
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In D'Amato et al. (2021), patients with and without cirrhosis exhibited similar reductions in ALP levels (29.4% vs. 34%; p = 0.53).
“Patients with cirrhosis showed a lower response rate than those without cirrhosis (29.5% vs. 49.2%; p = 0.01), largely due to a higher discontinuation rate in this group (30% vs. 12%; p = 0.004), although both groups exhibited similar reductions in ALP levels (29.4% vs. 34%; p = 0.53).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [28]
The Discussion (page not available) reports 12-month ALP reductions of 29.4% in patients with cirrhosis and 34% in those without, and says the difference was not significant. It does not give an exact p-value for that comparison. In Results, p = 0.53 refers instead to response rates under normal-range criteria. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn cohort studies in Spain and Portugal (n=120) and Italy (n=191), serum cholestatic enzymes were significantly reduced with obeticholic acid treatment, and 29.5% and 51.9% of patients met the POISE response criteria, respectively.
“Similarly, in other cohort studies in Spain and Portugal (n=120) and Italy (n=191), serum cholestatic enzymes were significantly reduced with obeticholic acid treatment, and 29•5% (Spain and Portugal cohort) and 51•9% (Italy cohort) of patients met the POISE response criteria.90,91”
From Primary biliary cholangitis. (2024) · cites this paper as [90]
The Discussion identifies a cohort of 191 patients from Italian centres and reports reductions in liver biochemistry with obeticholic acid. The Results (‘Response rate at 6 and 12 months’; page unavailable) report a 51.9% POISE response at 12 months, but only among treatment completers; the rate for the overall cohort was 42.9%. This source does not supply the Spain–Portugal cohort figures, which the citing sentence attributes alongside a separate citation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredReal-world data are gradually indicating an improvement in long-term prognosis with obeticholic acid.
“Regarding the long-term efficacy of obeticholic acid, real-world data are gradually indicating an improvement in long-term prognosis.[89][90][91][92][93]”
From Primary biliary cholangitis. (2024) · cites this paper as [90]
The Results (Response rate at 6 and 12 months) report improvements in alkaline phosphatase and bilirubin during real-world obeticholic acid treatment; the paper identifies these as markers associated with survival or better prognosis. Its follow-up was only 12 months, however, and it does not establish an improvement in long-term clinical prognosis. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn D'Amato et al. (2021), at 12 months, significant median reductions were observed in ALP (−32.3%), ALT (−31.4%), and bilirubin (−11.2%).
“At 12 months, significant median reductions were observed in ALP (−32.3%), alanine aminotransferase (ALT) (−31.4%), and bilirubin (−11.2%).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [28]
In D'Amato et al. (2021), patients with cirrhosis showed a lower response rate than those without cirrhosis (29.5% vs. 49.2%; p = 0.01).
“Patients with cirrhosis showed a lower response rate than those without cirrhosis (29.5% vs. 49.2%; p = 0.01), largely due to a higher discontinuation rate in this group (30% vs. 12%; p = 0.004), although both groups exhibited similar reductions in ALP levels (29.4% vs. 34%; p = 0.53).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [28]
In D'Amato et al. (2021), patients with PBC-AIH overlap had comparable response rates to those with PBC alone (46.4% vs. 42.3%; p = 0.68).
“Patients with PBC- autoimmune hepatitis (AIH) overlap had comparable response rates to those with PBC alone (46.4% vs. 42.3%; p = 0.68) but experienced greater reductions in ALT at 6 months (−38% vs. −29%; p = 0.04).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [28]
Overall, OCA was associated with reductions in ALP, ALT, and bilirubin at 12 months across the study population.
“Overall, OCA was associated with reductions in ALP, ALT, and bilirubin at 12 months across the study population.”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [28]
In D'Amato et al. (2021), patients with PBC-AIH overlap experienced greater reductions in ALT at 6 months than those with PBC alone (−38% vs. −29%; p = 0.04).
“Patients with PBC- autoimmune hepatitis (AIH) overlap had comparable response rates to those with PBC alone (46.4% vs. 42.3%; p = 0.68) but experienced greater reductions in ALT at 6 months (−38% vs. −29%; p = 0.04).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [28]
In D'Amato et al. (2021), patients with cirrhosis had a higher discontinuation rate than those without cirrhosis (30% vs. 12%; p = 0.004).
“Patients with cirrhosis showed a lower response rate than those without cirrhosis (29.5% vs. 49.2%; p = 0.01), largely due to a higher discontinuation rate in this group (30% vs. 12%; p = 0.004), although both groups exhibited similar reductions in ALP levels (29.4% vs. 34%; p = 0.53).”
From Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor (2025) · cites this paper as [28]
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- Authors
- D’Amato, D., De Vincentis, A., Malinverno, F., Viganò, M., Alvaro, D., Pompili, M., Picciotto, A., Palitti, V. P., Russello, M., Storato, S., Pigozzi, M. G., Calvaruso, V., De Gasperi, E., Lleo, A., Castellaneta, A., Pellicelli, A., Cazzagon, N., Floreani, A., Muratori, L., Fagiuoli, S., Niro, G. A., Feletti, V., Cozzolongo, R., Terreni, N., Marzioni, M., Pellicano, R., Pozzoni, P., Baiocchi, L., Chessa, L., Rosina, F., Bertino, G., Vinci, M., Morgando, A., Vanni, E., Scifo, G., Sacco, R., D’Antò, M., Bellia, V., Boldizzoni, R., Casella, S., Omazzi, B., Poggi, G., Cristoferi, L., Gerussi, A., Ronca, V., Venere, R., Ponziani, F., Cannavò, M., Mussetto, A., Fontana, R., Losito, F., Frazzetto, E., Distefano, M., Colapietro, F., Labanca, S., Marconi, G., Grassi, G., Galati, G., O’Donnell, S. E., Mancuso, C., Mulinacci, G., Palermo, A., Claar, E., Izzi, A., Picardi, A., Invernizzi, P., Carbone, M., & Vespasiani-Gentilucci, U.
- Affiliations
- Azienda Ospedaliera San Gerardo (IT)
- Ospedale San Giuseppe (IT)
- Sapienza University of Rome (IT)
- Agostino Gemelli University Polyclinic (IT)
- Ospedale Policlinico San Martino (IT)
- Ospedale Garibaldi (IT)
- Ospedale Sacro Cuore Don Calabria (IT)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- University of Palermo (IT)
- Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT)
- Azienda Ospedale - Università Padova (IT)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Ospedale Papa Giovanni XXIII (IT)
- Casa Sollievo della Sofferenza (IT)
- Ospedale "Santa Maria delle Croci" di Ravenna (IT)
- Gastroenterology Hospital "Saverio de Bellis" (IT)
- Ospedale Valduce (IT)
- Marche Polytechnic University (IT)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Alessandro Manzoni Hospital (IT)
- University of Rome Tor Vergata (IT)
- Azienda Ospedaliero-Universitaria Cagliari (IT)
- Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco" (IT)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Ospedali Riuniti di Foggia (IT)
- Azienda Socio Sanitaria Territoriale della Valtellina e Alto Lario (IT)
- Azienda Ospedaliera Treviglio (IT)
- Humanitas University (IT)
- Università Campus Bio-Medico (IT)
- Ospedale D. Cotugno (IT)
- Corresponding author
- Carbone, Marco
- ORCID
- D’Amato, Daphne
- Viganò, Mauro
- Alvaro, Domenico
- Pompili, Maurizio
- Russello, Maurizio
- Calvaruso, Vincenza
- Castellaneta, Antonino
- Pellicelli, Adriano
- Cazzagon, Nora
- Floreani, Annarosa
- Muratori, Luigi
- Fagiuoli, Stefano
- Niro, Grazia Anna
- Cozzolongo, Raffaele
- Marzioni, Marco
- Pellicano, Rinaldo
- Baiocchi, Leonardo
- Chessa, Luchino
- Bertino, Gaetano
- Vinci, Maria
- Sacco, Rodolfo
- Omazzi, Barbara
- Cristoferi, Laura
- Gerussi, Alessio
- Ronca, Vincenzo
- Ponziani, Francesca
- Mussetto, Alessandro
- Fontana, Rosanna
- Colapietro, Francesca
- Labanca, Sara
- Grassi, Giuseppe
- Galati, Giovanni
- Mancuso, Clara
- Mulinacci, Giacomo
- Palermo, Andrea
- Claar, Ernesto
- Izzi, Antonio
- Picardi, Antonio
- Invernizzi, Pietro
- Carbone, Marco
- Venue
- JHEP Reports
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 3
- Issue
- 2
- Pages
- 100248
- ISSN
- 2589-5559 (ISSN-L)
- PMC
- PMC7930359
- OpenAlex
- W3122123611
- Cited by
- 85
- References
- 9
- Citations by year
- 2026: 7 · 2025: 23 · 2024: 18 · 2023: 12 · 2022: 19 · 2021: 6
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- JHEP Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion, cc-by-nc-nd)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Ministero della Salute (GR-2018-12367794, PE-2016-02363915)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- obeticholic acid, primary biliary cirrhosis, real-world effectiveness, drug safety, treatment discontinuation, pruritus, liver cirrhosis, biochemical response, adverse events, second-line therapy
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