When to Switch to Second-Line Treatment for Primary Biliary Cholangitis?
In patients with primary biliary cholangitis (PBC), the response to ursodeoxycholic acid (UDCA) treatment is an important prognostic indicator. To identify patients with an insufficient response to this modality who require second-line therapy, the best practice is to assess the biochemical response to UDCA after 12 months of treatment. A validated and easy-to-use tool is the determination of serum alkaline phosphatase (ALP) activity and serum total bilirubin concentration. Although treatment response to UDCA is commonly checked after 12 months, a 6-month check has the same discriminatory value.
Determining Prognosis and Scoring Tools
PBC is a progressive disease with a high risk of developing liver cirrhosis, portal hypertension, and subsequently hepatocellular carcinoma. The prognosis of patients is determined at diagnosis based on age, sex, basic laboratory parameters (serum bilirubin and albumin concentrations), and the severity of liver impairment (according to histological examination or the degree of fibrosis determined by non-invasive methods).
The risk estimation tool MRS (Mayo Risk Score) is used to calculate the estimated risk, and the MELD score (Model for End-Stage Liver Disease) is added when considering liver transplantation. Both scores can be determined using the Mayo Clinic web calculator.
Therapeutic Response and Criteria for Changing Treatment
During PBC treatment, a significant prognostic parameter and indicator of the risk of further disease progression is the response to UDCA administration. The European Association for the Study of the Liver (EASL) suggests in its 2017 recommendations that in patients with an inadequate response to 12 months of UDCA treatment, obeticholic acid (OCA) should be considered as second-line therapy.
An inadequate response to UDCA is defined by the Toronto criteria as ALP > 1.67 times the upper limit of normal (ULN) or elevated serum total bilirubin concentration. This should not exceed 2 times the ULN, as there is still no available data on the efficacy and safety of OCA in patients in more advanced stages of the disease. When evaluating serum bilirubin, the potential presence of Gilbert's syndrome should also be considered.
It is also recommended to switch to OCA in patients who cannot take UDCA due to intolerance or hypersensitivity to the active substance.
Further Monitoring and Criteria for Continuing Treatment
After starting OCA, the patient should be monitored at least once every three months to assess the effectiveness of the treatment and the occurrence of any side effects. Continuing therapy with OCA is possible if, after three months, ALP decreases by at least 10%, no severe side effects are present, and after 12 months, serum ALP activity is ≤ 1.67 times ULN and total bilirubin concentration does not exceed 2 times ULN.
Note: The Ocaliva preparation containing the active substance OCA is reimbursed for the treatment of primary biliary cholangitis (also known as primary biliary cirrhosis) in combination with ursodeoxycholic acid in adult patients with an inadequate response to ursodeoxycholic acid or as monotherapy in adult patients who are intolerant to ursodeoxycholic acid treatment.
Treatment begins under one of the following conditions:
- Serum ALP activity > 1.67 times the upper limit of normal and/or elevated serum total bilirubin concentration < 2 times the upper limit of normal, with treatment lasting at least 12 months with ursodeoxycholic acid at therapeutic doses.
- Intolerance to ursodeoxycholic acid is documented in the records.
Treatment is terminated under one of the following conditions:
- If there is no decrease in serum ALP activity by > 10% from baseline levels at the third month of treatment.
- If, after 12 months of uninterrupted treatment with obeticholic acid (and then every six months thereafter, i.e., in the 18th month, 24th month, etc.), serum ALP activity > 1.67 times the upper limit of normal and/or serum total bilirubin concentration exceeds the upper limit of normal.
- If severe side effects occur at any time during treatment. The success of therapy must be regularly reassessed at 3, 6, and 12 months of treatment (and thereafter every six months) and recorded in medical documentation.
The Ocaliva preparation can only be prescribed by selected specialized centers, the list of which can be found on the proLékaře.cz website.
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Sources:
1. Fejfar T., Vaňásek T., Hůlek P. et al. Primary biliary cholangitis - recommended guidelines of the Czech Hepatological Society CLS JEP for diagnosis and treatment. Gastroenterology and Hepatology 2018; 72(2): 109–118.
2. Indication restrictions for Ocaliva reimbursement. Available at: www.sukl.cz/modules/medication/detail.php?code=0219168&tab=prices
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