Seladelpar Linked to Sustained IL-31 Reduction in PBC in New Study

Seladelpar was associated with sustained reductions in interleukin-31 (IL-31) through 36 months in patients with primary biliary cholangitis (PBC), with larger cytokine decreases among those reporting meaningful pruritus improvement, according to an ASSURE analysis presented at The Liver Meeting 2026.¹

Marlyn Mayo, MD, professor of internal medicine at UT Southwestern Medical Center in Dallas, discussed the findings in an interview with HCPLive. She emphasized that pruritus can cause depression, social isolation, and perceived stigma, while uncertainty about its underlying mechanisms continues to complicate treatment.

The post hoc analysis included 284 patients treated with seladelpar 10 mg daily, including 93 with baseline pruritus numerical rating scale (NRS) scores ≥4. Patients entered the open-label ASSURE study (NCT03301506) from RESPONSE or earlier seladelpar trials.¹

At month 36, least-squares mean IL-31 reductions reached 68% overall and 74% among patients with baseline NRS scores ≥4. Patients with ≥3-point NRS improvements had larger median IL-31 reductions than those with less improvement.¹

Mayo highlighted the durability of these findings, which extended earlier evidence connecting seladelpar-associated IL-31 reductions with itch improvement.² Maintaining cytokine suppression for years was notable, she explained, given the dynamic nature of cytokine signaling.

However, Mayo cautioned against interpreting IL-31 as a biomarker ready for clinical use. Although higher baseline concentrations correlated with greater itch severity, there was variability, and levels could not reliably distinguish patients by symptom burden.

“What matters is whether the patient's getting better or not,” Mayo said.

The open-label, post hoc findings supported a possible mechanistic link but did not establish that lowering IL-31 caused pruritus improvement. Mayo said future research should examine how cytokine, opioid, serotonergic, and other pathways interact, particularly because existing therapies often reduce itching without eliminating it. For primary care physicians, her comments underscored the importance of assessing patients’ symptoms when evaluating improvement.

References:

1. Mayo M, Kwon KM, Hirschfield G, et al. Seladelpar leads to durable and significant decrease in the pruritogenic cytokine IL-31, associated with pruritus improvement: long-term data from the ASSURE study. Presented at: The Liver Meeting 2026; Denver, CO. Abstract 1233.
2. Kremer AE, Mayo MJ, Hirschfield GM, et al. Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis. Hepatology. 2024;80(1):27-37. doi:10.1097/HEP.0000000000000728