For adults with primary biliary cholangitis (PBC)1
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For adults with primary biliary cholangitis (PBC)1
PBC is a chronic, progressive autoimmune liver disease that leads to the inflammation and scarring of the small bile ducts in the liver—it can eventually result in cirrhosis if left inadequately treated.2,3
The exact cause of PBC is not known—most researchers believe it’s a mix of genetics and environmental factors. It’s important to reassure your patients that a PBC diagnosis is not their fault.2
A primary goal of PBC treatment is to prevent end-stage liver disease, liver transplant, or death.4,5 To achieve this goal, the focus should be both normalization or near-normalization of key biomarkers and prevention of fibrosis progression.6,7
If left inadequately treated, PBC can lead to end-stage liver disease, liver transplant, or death.2 You can stay on top of your patients’ disease progression by monitoring their biomarkers every 3 to 6 months, and fibrosis progression every 12 or 24 months, depending on their treatment response.8,9
Five to ten percent of patients with PBC experience a very rapid onset of ductopenia and severe icteric cholestasis, progressing very quickly towards cirrhosis in less than 5 years.2 Furthermore, up to 30% of patients can have a severe progressive form of PBC, resulting in early development of liver fibrosis and liver failure.10 Experiences with PBC can vary significantly, and this heterogeneity of progression means it’s important to keep regular track of each individual patient’s biomarker levels and fibrosis progression.6 This also means that early diagnosis and treatment of PBC is essential.10
Every patient is different, so it’s up to each clinician to take a holistic look at their patients when assessing for and diagnosing PBC. According to current clinical guidelines, a diagnosis of PBC can be established when two of the following three criteria are met11:
A liver biopsy should be considered in some cases.11
Early diagnosis, treatment, and monitoring of key biomarkers is critical to help prevent progression to end-stage liver disease.4,12 An increase in ALP and GGT can indicate early stages of cholestasis. Bilirubin can be elevated in later stages of the disease.4,6 Elevated AST and ALT can indicate hepatocellular damage and further inflammation of the liver. And a decrease in albumin and platelets can be a sign of a cirrhotic liver, or end-stage liver disease.4,8
Expert guidance recommends monitoring fibrosis progression every 12 or 24 months, depending on your patient’s response to treatment.9
OCALIVA acts differently than UDCA.1 Unlike UDCA, it activates the farnesoid X receptor (FXR), which both inhibits bile acid synthesis and increases bile acid secretion.1,13
FXR is a nuclear receptor expressed in the liver and intestine that inhibits bile acid synthesis and increases bile acid secretion at the transcriptional level, reducing hepatic exposure to bile acids. In addition, FXR is a key regulator of inflammatory, fibrotic, and metabolic pathways.14 OCALIVA is an FXR agonist.1
Yes—in the pivotal trial, 7% of patients were not on UDCA due to intolerance and received OCALIVA alone as monotherapy.1
OCALIVA has been helping patients with PBC since 2016, making it the first FDA-approved add-on treatment for PBC.1
Some patients saw a reduction in their ALP levels as early as 2 weeks after starting OCALIVA, and were maintained through month 12 when kept on the same dosage.1
When OCALIVA was added on in a 12-month clinical study, nearly 5x more patients achieved a reduction in PBC disease activity, as defined by the primary composite endpoint: ALP <1.67x ULN, ALP decrease of ≥15%, and total bilirubin ≤ULN.1
Yes. After the 12-month clinical trial, a subset of patients—including the placebo group—switched to OCALIVA for an additional 5 years in an open-label extension portion of the study. There were additional reductions observed across fibrosis and key biomarkers of PBC, but since this was a post-hoc analysis, these results are exploratory, and no clinical conclusions should be made.1,15-17
The most common side effects of OCALIVA are pruritus (itchy skin), fatigue, abdominal pain and discomfort, rash, arthralgia, oropharyngeal pain, dizziness, constipation, peripheral edema, palpitations, pyrexia, thyroid function abnormality, and eczema.1
Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with either compensated or decompensated cirrhosis.1
OCALIVA is taken orally once daily, with or without food.1
The recommended starting dosage of OCALIVA is 5 mg orally once daily for 3 months with titration to 10 mg once daily based upon tolerability and response.1
Yes. OCALIVA is contraindicated in patients with1:
Be sure to routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether drug discontinuation is needed.1
Discontinue OCALIVA in patients who1:
If severe intercurrent illness occurs, interrupt treatment with OCALIVA and monitor the patient’s liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting OCALIVA treatment.1
It’s important to be aware of any other medications your patients may be on.
Bile acid binding resins may reduce the absorption, systemic exposure, and efficacy of OCALIVA. Co-administration of warfarin and OCALIVA decreases international normalized ratio (INR). OCALIVA may increase exposure to concomitant drugs that are CYP1A2 substrates with a narrow therapeutic index. Inhibitors of bile salt efflux pump may exacerbate accumulation of conjugated bile salts, including taurine conjugate of OCALIVA in the liver and result in clinical symptoms.1
While pruritus can be a side effect of OCALIVA, it is also a common symptom of PBC.1,11 In fact, 60% of those in the POISE clinical study had a baseline history of pruritus prior to adding on OCALIVA.1 If your patients are concerned about experiencing pruritus, you can talk them through some ideas to help manage their itching, like staying hydrated, trying out relaxation techniques, taking cool showers, and more.18-20
Plus, there are resources you can provide to help them manage their pruritus.
Fatigue is reported in up to 78% of patients with PBC. When severe, it can affect their quality of life.6 If your patients are experiencing fatigue with their PBC, you can advise them on management techniques like avoiding social isolation and trying structured exercise routines.4
Ninety-nine percent of eligible patients with PBC pay $0 for their prescription when a copay card is applied.21,a And 9 out of 10 Medicare patients are covered for OCALIVA, too.22,b You can also point your patients towards Interconnect® Support Services, a program dedicated to helping your patients start and stay on therapy through personalized and comprehensive support.
Yes! Interconnect® Support Services helps support your patients through their OCALIVA journey, and is also here to help you and your staff through the process. It’s easy to enroll your patients.
Yes! We have a range of brochures and handouts available, both to support you and your staff, and for you to provide to your patients as helpful takeaway materials.
aOffer not valid for patients enrolled in Medicare, Medicaid, or other federal or state healthcare programs.
bBased on 97.6% of all Medicare patients prescribed OCALIVA whose prior authorizations were approved in calendar year 2022.22
ALP, alkaline phosphatase; ALT, alanine transaminase; AMA, antimitochondrial antibody; AST, aspartate aminotransferase; FXR, farnesoid X receptor; GGT, gamma-glutamyl transferase; OLE, open-label extension; TE, transient elastography; UDCA, ursodeoxycholic acid; VCTE, vibration controlled transient elastography.
WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS
WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS
OCALIVA, a farnesoid X receptor (FXR) agonist, is indicated for the treatment of adult patients with primary biliary cholangitis (PBC)
either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA.
This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OCALIVA is contraindicated in patients with:
Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with cirrhosis, either compensated or decompensated. Among postmarketing cases reporting it, median time to hepatic decompensation (e.g., new onset ascites) was 4 months for patients with compensated cirrhosis; median time to a new decompensation event (e.g., hepatic encephalopathy) was 2.5 months for patients with decompensated cirrhosis. Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dosage for that patient population; however, cases of hepatic decompensation and failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dosage.
Hepatotoxicity was observed in the OCALIVA clinical trials. A dose-response relationship was observed for the occurrence of hepatic adverse reactions including jaundice, worsening ascites, and primary biliary cholangitis flare with dosages of OCALIVA of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with OCALIVA in two 3-month, placebo-controlled clinical trials in patients with primarily early stage PBC.
Routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether drug discontinuation is needed. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time to determine whether drug discontinuation is needed. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy), have compensated cirrhosis and develop evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. If severe intercurrent illness occurs, interrupt treatment with OCALIVA and monitor the patient’s liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting OCALIVA treatment.
Severe pruritus was reported in 23% of patients in the OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arm in a 12-month double-blind randomized controlled clinical trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. Consider clinical evaluation of patients with new onset or worsening severe pruritus. Management strategies include the addition of bile acid binding resins or antihistamines, OCALIVA dosage reduction, and/or temporary interruption of OCALIVA dosing.
Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C). Dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in OCALIVA-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to OCALIVA after 1 year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment.
The most common adverse reactions (≥5%) are: pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema.
Please click here for Full Prescribing Information, including Boxed WARNING.
To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
If you have questions or would like more information about OCALIVA, contact Intercept Medical Information.