Marlyn Mayo, MD, is a professor of internal medicine at UT Southwestern Medical Center.

Marlyn Mayo, MD

 treatment landscape was limited to just a handful of agents with limited efficacy. However, to the excitement of clinicians and patients alike, 2024 saw a major shift in PBC management with the addition of 2 new second-line therapies: elafibranor (Iqirvo) and seladelpar (Livdelzi).

The proliferator-activated receptor (PPAR) agonists earned accelerated approval from the US Food and Drug Administration in June and August, respectively. Whereas obeticholic acid used to be the only other option for patients who do not respond to or cannot tolerate first-line ursodeoxycholic acid, elafibranor and seladelpar offer long-awaited choices for patients who do not benefit from these traditional PBC therapies.

In addition to greatly expanding the PBC treatment landscape, the approvals of elafibranor and seladelpar also provide patients with treatment options that target one of the most common but underrecognized and subsequently undertreated symptoms of PBC: pruritus.

Despite studies reporting pruritus occurrence in 50-80% of PBC cases, Marlyn Mayo, MD, a professor of internal medicine at UT Southwestern Medical Center, explained to 

 how clinicians often underestimate both its prevalence and impact, as evidenced by disparities between patient-reported and physician-assessed pruritus severity. Beyond discomfort, she explained how itch has a profound effect on quality of life, contributing to sleep disturbances, fatigue, anxiety, depression, and functional impairments, including missed work and social isolation.

Marlyn Mayo, MD: Improving Pruritus Management in PBC Care

“Our traditional [PBC] therapies don't help with itch at all and may in fact make it worse,” Mayo said, describing the different guideline-recommended therapies for addressing pruritus in PBC but calling attention to the fact that none of them are universally efficacious.

However, elafibranor and seladelpar may offer viable treatment options for treating both the underlying disease as well as the itch associated with it.

“This is a really exciting time,” Mayo emphasized. “We have just had 2 new drugs approved in the US by the FDA for second-line treatment of PBC, elafibranor and seladelpar, and both of those medications seem to have a beneficial effect on pruritus… For some patients, that might be enough to treat the underlying disease as well as the itching.”

Mayo also expressed optimism about recent advancements in the development of ileal bile acid transporter (IBAT) for treating itch in PBC, with phase 3 trials nearing completion and potentially offering hope for broader application beyond their currently approved pediatric indications.

She went on to emphasize the importance of a nuanced and patient-centered approach to pruritus assessment in patients with PBC, noting the importance of moving beyond binary questioning about the presence of itching to detailed discussions of its severity, quality-of-life impacts, and patient preferences for treatment. Mayo also cites the need for early intervention with guideline-recommended pruritus-directed therapies, especially in patients with severe pruritus who cannot wait the typical 6-12 months to evaluate response to first-line treatment before initiating an itch-effective second-line option like elafibranor or seladelpar.

Editors’ note: Mayo has relevant disclosures with CymaBay, GENFIT, Gilead, GlaxoSmithKline, Ironwood, Intercept, Ipsen, and Mirum.

Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed December 9, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed December 9, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

Videos

The treatment landscape for primary biliary cholangitis (PBC) has significantly evolved with the FDA's accelerated approval of elafibranor and seladelpar as second-line therapies. These PPAR agonists offer new options for patients unresponsive to first-line ursodeoxycholic acid, addressing both the disease and pruritus, a common yet often underestimated symptom. The advancements highlight the need for a patient-centered approach to pruritus assessment and early intervention. Additionally, ongoing developments in ileal bile acid transporter therapies may further enhance treatment options for PBC-related itch.

Mayo explains current shortcomings of pruritus care in PBC and what the additions of elafibranor, seladelpar, and other agents in development may offer.

Marlyn Mayo, MD

Articles