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PBC in the Real World
PBC in the Real World: Recent Evidence for Second-line PPAR Agonists

Released: June 19, 2026

Maria Londoño
Maria Londoño, MD, PhD
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Key Takeaways
  • In real-world settings, effectiveness of PBC treatment with PPAR agonists was consistent with that reported in phase III studies.
  • In people with prior second-line treatment for PBC, switch to PPAR agonists was generally associated with improvement in ALP levels and biochemical response, although some people with prior UDCA, OCA, and bezafibrate lost their biochemical response.
  • In people with ALP that is only mildly elevated, PPAR agonists were associated with high rates of biochemical response and ALP normalization.

It is an exciting time to be treating people with primary biliary cholangitis (PBC). For years, ursodeoxycholic acid (UDCA) was essentially the only treatment option available. Although highly effective for many people, a substantial proportion failed to achieve an adequate biochemical response on UDCA, leaving healthcare professionals (HCPs) with limited alternatives.

At the 2026 European Association for the Study of the Liver (EASL) Congress, a growing body of real-world evidence showed that the newer peroxisome proliferator–activated receptor (PPAR) agonists elafibranor and seladelpar are delivering meaningful results outside the controlled environment of clinical trials.

Real-world Evidence
One of the most reassuring messages from EASL 2026 is that the effectiveness observed in clinical trials appears to be translating into routine clinical practice.

Real-world data with seladelpar demonstrated high rates of biochemical response and alkaline phosphatase (ALP) normalization across a broad spectrum of people, including those with overlapping PBC and autoimmune hepatitis and coexisting PBC and metabolic dysfunction–associated steatotic liver disease variants. Although response rates were lower in participants with cirrhosis compared with those without, meaningful benefits were observed across all subgroups.

Similarly, early real-world experience with elafibranor has been encouraging. In the prospective phase IV ELFINITY study, more than one half of all participants achieved biochemical response within the first 3 months of treatment. 

What particularly caught my attention was the growing focus on outcomes that matter directly to patients. Pruritus and fatigue remain 2 of the most burdensome symptoms in PBC, often affecting quality of life more than laboratory abnormalities. Both elafibranor and seladelpar have evidence from earlier clinical trials suggesting they can improve symptoms, and in the real-world phase IV ELFINITY trial, clinically meaningful improvements were observed across several validated measures of pruritus and fatigue. These data suggest that the benefits of PPAR agonists may extend beyond biochemical control.

Switch From OCA
Another key theme at EASL 2026 was the use of PPAR agonists in treatment-experienced patients. This topic gained relevance following the withdrawal of obeticholic acid (OCA) in Europe and the United States, prompting many HCPs to reconsider therapeutic strategies for people previously receiving this second-line treatment.

Encouragingly, real-world data suggest that both elafibranor and seladelpar remain effective options in this setting. Data from the Italian Early Access Program and the Spanish ColHai registry showed meaningful reductions in ALP and improvements in biochemical response after switch from OCA or bezafibrate to a PPAR agonist.

At the same time, these studies remind us that not all treatment-experienced populations respond the same. In the ColHai registry, people previously receiving triple therapy with UDCA, OCA, and bezafibrate appeared to represent the most challenging subgroup. A considerable proportion lost their biochemical response after discontinuation of triple therapy, highlighting the difficulty of maintaining disease control in individuals with more advanced or refractory disease. Although PPAR agonists are clearly an effective second-line therapy, these findings suggest that people transitioning away from triple therapy may require closer monitoring and remain an area of unmet need.

People With Mildly Elevated ALP
Perhaps the most intriguing data presented this year involved people with ALP levels between 1.00 and 1.67 times the upper limit of normal. Historically, these people with PBC have fallen into a therapeutic gray zone because they would not have qualified for many pivotal clinical trials.

However, several analyses suggest that they may still derive substantial benefit from treatment intensification. Real-world data with elafibranor and seladelpar demonstrated significant reductions in ALP and high rates of ALP normalization, even among people whose baseline ALP was below the traditional treatment threshold.

Complementing these findings, long-term data from ASSURE showed that biochemical response to seladelpar was associated with stable or improved liver stiffness measurements over time. Although additional data are needed, these results strengthen the link between biochemical control and potential disease modification.

Taken together, these studies reinforce the idea that the treatment landscape in PBC is evolving rapidly. The real-world evidence is not only confirming what we observed in clinical trials but also expanding our understanding of how these therapies perform in more diverse and complex populations. The challenge is no longer whether we have treatment options; it is how to use them optimally and early enough to maximize long-term benefit for people with PBC.

Your Thoughts
Considering these updated clinical trial and real-world data, what are your thoughts on treatment intensification with PPAR agonists for people with PBC and mildly elevated ALP who fall into the therapeutic “gray zone”? Leave a comment to join the discussion!