Second-Line Obeticholic Acid for PBC Used Infrequently and with Delays

Sonal Kumar, MD, MPH

Credit: Twitter

Obeticholic acid (Ocaliva) is being infrequently used as a second-line therapy in eligible patients with primary biliary cholangitis (PBC), according to new findings—and even among those that it’s being used, a considerable delay to initiating it may result in progression to poor outcomes including cirrhosis.

In new data presented at the American College of Gastroenterology (ACG) 2024 Scientific Sessions in Philadelphia, PA, this week, a team of investigators supported by Intercept Pharmaceuticals found that fewer than 8% of patients with PBC eligible for second-line therapy actually initiated obeticholic acid care; the mean time from initiating said care since becoming eligible for it was more than 1 year. The findings highlight a persistent gap in timely, effective care for patients with worsening state from the cholestatic disease.

The research team led by Sonal Kumar, MD, MPH, of Weill Cornell Medical College in New York, sought to estimate the time from second-line therapy eligibility to the initiation of obeticholic acid in patients with PBC. Obeticholic acid is currently 1 of 3 second-line therapies approved by the US Food and Drug Administration (FDA) to treat PBC, the others being elafibranor (Iqirvo) and seladelpar (Livdelzi). Obeticholic acid was originally indicated for use as a second-line treatment in PBC under an accelerated approval in 2016, but it remains without a full approval as of October 2024.

Investigators identified patients with PBC via Komodo Health database. Eligible patients had 1 inpatient or ≥2 outpatient claims for their condition and were eligible for second-line PBC therapy, defined as an inadequate response to ursodeoxycholic acid, between June 2016 and February 2022.

The team used first date of second-line therapy eligibility as index; patients were enrolled for ≥12 months pre-index and were ≥18 years old at index. Patients were followed until the first to occur between obeticholic acid initiation; end of insurance enrollment; longterm care admission; death; or end of study in May 2023.

The final assessment included 3880 adult patients with PBC who were defined as eligible for second-line therapy between 2016 – 2022. Mean patient age was 61.0 years old; 90.8% were female and approximately half (50.5%) were White.

Among the eligible patients, only 306 (7.9%) initiated obeticholic acid second-line therapy. Mean time to treatment from index was 14.2 months, or a median of 10.2 months (IQR, 2.8 – 18.1). Patients who did initiate obeticholic acid therapy were slightly younger (mean age, 57.2 years vs 61.3 years), and were similar proportions of female (90.7%) and White (42.1%).

In the 12 months prior to and including index date, a greater rate of patients with PBC who initiated obeticholic acid had cirrhosis than those who did not initiate (17.6% vs 12.4%). They were also more likely to have an autoimmune disease (29.3% vs 26.3%). The proportion of patients with cirrhosis was nearly doubled at the time of second-line therapy initiation versus the index of when they first became eligible for it (31.4% vs 17.6%).

Kumar and colleagues additionally observed that patients initiating obeticholic acid had higher mean baseline alkaline phosphatase (ALP) levels than those who did not, and that two-thirds (65.3%) of patients had ALP levels >1.67 times the upper limit of normal by the time of initiated second-line therapy.

Investigators concluded that, among eligible adult patients with PBC since 2016, approximately 1 in 12 actually initiated second-line obeticholic acid therapy, “with a considerable delay observed.”

“This delay suggests patients may experience disease progression, including cirrhosis, before starting second-therapy therapy,” they wrote. “Timely initiation of obeticholic acid in appropriate patients could enhance its clinical benefit on long-term outcomes.”

References

1. ^{Kumar S, MacEwan JP, Levine A, Bessonova L, et al. Time to Initiation of the Second-Line Therapy Obeticholic Acid in Patients With Primary Biliary Cholangitis. Abstract presented at: American College of Gastroenterology (ACG) 2024 Scientific Sessions. Philadelphia, PA. October 25 – 30, 2024.}
2. ^{Brooks A. FDA Extends Review of Obeticholic Acid (Ocaliva) sNDA for Primary Biliary Cholangitis. HCPLive. Published online October 17, 2024. https://www.hcplive.com/view/fda-extends-review-obeticholic-acid-ocaliva-snda-primary-biliary-cholangitis}