OCA in Second-Line Treatment of PBC: Analysis Results and Real-World Data

Introduction

Since May 2019, OCA in the Czech Republic is covered by public health insurance as a specially accounted medicinal product that is prescribed in centers under the VILP regime, meaning there is an obligation to store data in the registry. It is used in combination with UDCA in patients with PBC who did not achieve an adequate response to UDCA, and in monotherapy for those who did not tolerate UDCA.

Obeticholic acid is a potent selective agonist of the farnesoid X receptor (FXR). This nuclear receptor influences the synthesis and absorption of bile acids, production of inflammatory and anti-inflammatory mediators, and potentially suppresses fibrosis-related processes.

Results of the Combined POISE and POISE OLE Analysis

OCA was registered based on data from the double-blind phase III POISE study, which continued with an open-label extension (OLE). Their combined analysis confirmed the long-term efficacy and safety of obeticholic acid (after 72 months of treatment). The drug slowed disease progression, with liver stiffness stabilization (demonstrated by FibroScan), indicating no increased risk of complications.

The concept of liver stiffness was highlighted by the author of the presentation at the XLVIII May Hepatology Days, Associate Professor Jan Šperl, MD, Ph.D., from the Clinic of Hepatogastroenterology IKEM in Prague, as a controlling parameter with respect to the patient's future clinical condition: “If liver stiffness, though not improving, remains stable, the patient's clinical condition should remain stable. With age and continuing disease, the risk of liver complications or death should not increase.” According to him, it seems that obeticholic acid offers new hope for patients who do not tolerate ursodeoxycholic acid or do not respond adequately to it.

Data from Clinical Practice

So far, three patient cohorts have been evaluated in real-world practice – Italian, Canadian, and French cohorts.

Italian Cohort

The first group consisted of 191 patients treated in Italy and followed for longer than 12 months. Fifteen percent had an overlap of PBC and autoimmune hepatitis, and 32% already had cirrhosis. The presence of cirrhosis and overlapping syndrome was confirmed as a predictive factor for a worse course even when OCA was administered. A decrease in the monitored biochemical parameters was confirmed in patients with and without cirrhosis. The efficiency curves over the mentioned 12 months completely correspond with the findings of the registration study (an initial sharper decline in monitored parameters followed by a relatively gradual decline).

The most frequently observed adverse reaction was pruritus. It was the reason for treatment discontinuation in 17% of patients, while in the POISE study, it was 9%; however, the condition of patients in this real-world cohort was significantly more advanced.

Canadian Cohort

The Canadian cohort consisted of 64 patients with an average age of over 55 years. A significant portion had relatively high liver stiffness, and 24% had cirrhosis. Initially, there was a sharper decline in the values of the monitored indicators, followed by a slowdown. The proportion of patients with a complete response continuously increased. A 20% reduction in ALP was significant at all evaluated points between the 3rd and 15th months, with some stabilization in the 6th month, and persisted even after 1 year of treatment. Bilirubin levels remained stable, and other parameters (ALT, AST, and IgM) decreased. Most criteria for evaluating treatment efficacy are based on ALP levels, which indicate the patient's future.

French Cohort

The French study monitored 76 patients whose average liver stiffness value already exceeded the value typical for cirrhosis. Results show the same trend as in the above-mentioned cohorts. In the 12th month, ALT, AST, and bilirubin concentrations improved. A significant proportion of patients with pruritus was again observed. These real-world data confirmed compatibility with the registration study data and its extended phase.

Conclusion

Thus, obeticholic acid has demonstrated efficacy, safety, and tolerability in patients with PBC not only in clinical studies but also in real-world practice. Even in patients with advanced liver fibrosis who did not respond to UDCA, significant improvements in biochemical indicators and stabilization of liver stiffness were observed after initiating OCA treatment.

Eva Srbová
editorial staff of proLékaře.cz