After 20 years, a new treatment option for primary biliary cholangitis arrives
Primary biliary cholangitis (PBC), formerly known as cirrhosis, is a rare disease with a negative impact on prognosis and quality of life. While ursodeoxycholic acid (UDCA) has been essentially the only treatment option for PBC so far, in 2016, the European Medicines Agency (EMA) approved obeticholic acid as a second-line option. Since 2019, this medication has been available and fully covered by health insurance in 11 selected centers in the Czech Republic.
Existing treatment does not help everyone
PBC is a rare autoimmune disease of unknown origin, primarily affecting women. The inflammation of the intrahepatic bile ducts results in progressive fibrotic remodeling of the liver, which can lead to liver failure and the need for transplantation, hence the older term “primary biliary cirrhosis” that is no longer used.
Early diagnosis and effective pharmacotherapy are crucial for improving the otherwise very unfavorable prognosis of patients with PBC. Since 1997, ursodeoxycholic acid (UDCA) has been used as the first-line treatment, effectively slowing disease progression, delaying or preventing the need for liver transplantation, and reducing mortality.
However, some patients do not tolerate UDCA treatment or only partially or not at all respond to it. This is manifested in practice mainly by the insufficient decrease in ALP and total bilirubin levels in the serum. Depending on the evaluation criteria used, an inadequate response to UDCA can affect 20–50% of patients with PBC.
The arrival of obeticholic acid: the POISE study
These patients were the subjects of the POISE study, which laid the foundation for the approval of obeticholic acid (OCA), offering new hope for patients with PBC. A total of 217 participants were randomized to take UDCA with a placebo, OCA at a dose of 5 mg gradually increased to 10 mg, or straight OCA at a dose of 10 mg. Treatment success was evaluated by a rather strict primary combined endpoint, which included a reduction in ALP levels by at least 15%, achieving an ALP level of ≤ 1.67 times the upper limit of normal, and reaching normal bilirubin levels.
After one year of treatment, 46% of patients treated with UDCA + OCA achieved the primary endpoint, compared to only 10% of patients solely on UDCA. Additionally, a positive impact of OCA treatment on secondary parameters, such as decreased activity of other liver enzymes, reduced concentration of immunoglobulins, pro-inflammatory cytokines, plasma concentrations of bile acids, and plasma markers of fibrosis, was observed. The increased incidence of pruritus observed in the first months of OCA treatment normalized within half a year and was no different from patients with placebo.
The POISE study continued with an open-label follow-up after 12 months, during which all patients took OCA at a dose of 5 mg gradually titrated to 10 mg. The observed beneficial effect of the treatment persisted throughout the follow-up. In patients who added OCA to their therapy only during the open-label follow-up, the effect of the combined treatment became noticeable within the first 3 months and gradually, this group approached the results of individuals already treated with OCA. Further related studies identified the beneficial impact of combination therapy on histological findings or the risk score for transplantation and mortality in patients with PBC.
New hope for the timely and correctly diagnosed
Obeticholic acid as a second-line treatment in cases of ineffective or intolerable UDCA became part of the recommended guidelines by the European Association for the Study of the Liver (EASL) in 2017 and appeared in the recommendations of the Czech Hepatology Society of CLS JEP a year later. Public health insurance has covered the medication since May 2019 in the Czech Republic. This new treatment option not only emphasizes the importance of timely diagnosis of PBC but also raises the significance of assessing patient response to first-line treatment and, if ineffective, utilizing combination therapy. Early addition of obeticholic acid and titration to a sufficiently effective dose can have a crucial impact on the patient's quality of life and prognosis. Currently, prescription is limited to 11 specialized centers in the Czech Republic.
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Source: Křemen J. New hope in the treatment of primary biliary cholangitis. Profi medicina 2019; 12.
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