Craig Lammert, MD, is an associate professor of medicine at Indiana University School of Medicine and executive director for the Autoimmune Hepatitis Association. 

Craig Lammert, MD

Advancing Autoimmune Hepatitis Treatment and Research, with Craig Lammert, MD

 treatment landscape has remained stagnant, relying on the same standard therapies with little innovation.

AIH is a rare chronic disease, with little known about its etiology and pathophysiology. Additionally, epidemiological data on AIH is scarce and likely unreported and underrecognized.

“The standard of care that we've been using for almost 70 years really has not evolved,” Craig Lammert, MD, an associate professor of medicine at Indiana University School of Medicine and executive director for the Autoimmune Hepatitis Association, explained to 

. “We have very much used azathioprine, or Imuran, as a hammer and the patients as a nail.”

He notes that recent studies have sought to widen the standard of care, specifically referencing the CAMARO trial comparing azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with AIH. Results showed mycophenolate mofetil with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks with fewer adverse events compared to azathioprine combined with prednisolone.

Still, Lammert points out a significant proportion of patients fail to achieve biochemical response with currently available therapies and face long-term corticosteroid dependence.

“Anything we can do to herald in a new wave of clinical trials, and how we design those trials to not suffer from what we've seen in the PBC space, but also to identify agents and test them in a way to get full approval, would be tremendously impactful for autoimmune hepatitis patient populations,” he said.

In the meantime, Lammert describes efforts to optimize current standard of care and assess tools for long-term disease monitoring, including FibroScan.

“More to come on this area, and again, an exciting area, but we need so much more collaboration and patient-level data,” he said. “I think this will help guide us into the future, and hopefully, autoimmune hepatitis will catch up with all the other autoimmune diseases in terms of treatment and more individualized level of care.”

Editors’ note: Lammert has relevant disclosures with Eli Lilly, Kezar Life Sciences, and the Autoimmune Hepatitis Association.

Linzay CD, Sharma B, Pandit S. Autoimmune Hepatitis. StatPearls. August 14, 2023. Accessed March 25, 2025. 

https://www.ncbi.nlm.nih.gov/books/NBK459186/

Snijders RJALM, Stoelinga AEC, Gevers TJG, et al. An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis. 

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Lammert describes the lack of developments in autoimmune hepatitis care over the past several decades and points to what might be next in disease management.

Navigating Evolutions, Uncertainties in PBC Care, with Craig Lammert, MD

 saw the addition of 2 new second-line treatment options with the FDA accelerated approvals of Ipsen’s elafibranor (Iqirvo) and Gilead’s seladelpar (Livdelzi).

A chronic and progressive autoimmune liver disease affecting intrahepatic bile ducts, common symptoms of PBC include ​​jaundice, pruritus, and fatigue. Ursodeoxycholic acid has long been the mainstay of treatment for PBC and continues to be the only first-line therapy. However, many patients do not respond to or are unable to tolerate it, underscoring the need for more treatment options to prevent progression to cirrhosis and eventual liver failure as well as to improve symptoms most negatively impacting patients.

, Craig Lammert, MD, an associate professor of medicine at Indiana University School of Medicine and executive director for the Autoimmune Hepatitis Association, discusses the adoption of elafibranor and seladelpar in clinical practice and barriers to their uptake.

He says that while clinical trial data for both agents has translated well into real-world practice, access remains a significant issue, with many insurance plans delaying coverage for newly approved medications by 6 months to more than a year and leaving clinicians with difficult decisions about whether to wait or use alternative therapies.

Lammert goes on to highlight what he refers to as "alkaline phosphatase purgatory"—those with persistently elevated but not severely abnormal alkaline phosphatase levels. This group, comprising nearly a third of PBC patients, often does not qualify for new second-line treatments despite evidence suggesting they remain at higher risk for liver-related complications, particularly if bilirubin levels exceed 0.6 mg/dL.

He notes that understanding the impact elafibranor and seladelpar have on quality of life will also be important, acknowledging that while disease control and transplant avoidance are critical goals, addressing pruritus and fatigue are important to patients and must also be prioritized.

Looking ahead, Lammert emphasizes that it will be important to consider what can be done for patients beyond the “therapeutic ceiling” of these new agents as well as to explore dual agent therapy or additive therapies to “rescue” difficult-to-treat patients.

The Evolving Primary Biliary Cholangitis Landscape, with Craig Lammert, MD

Brooks A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. 

. June 10, 2024. Accessed March 24, 2025. 

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. 

. August 14, 2024. Accessed March 24, 2025. 

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

Lammert describes the clinical impact of having 2 new second-line PBC therapies, challenges to their uptake, and areas where more research is needed.

 saw the addition of 2 new second-line treatment options with the FDA accelerated approvals of elafibranor (Iqirvo) and seladelpar (Livdelzi).

, Craig Lammert, MD, an associate professor of medicine at Indiana University School of Medicine and executive director for the Autoimmune Hepatitis Association, outlines the shifting landscape of treatment response metrics and the latest advancements in second-line therapy for PBC.

He begins by highlighting how traditional biochemical response criteria may not fully predict long-term clinical benefits. Specifically, Lammert points to use of the Toronto criteria, 1.67 x upper limit normal alkaline phosphatase at 1 year, to predict patients who will do well on ursodeoxycholic acid, noting that meeting this criteria has not always been linked with good long-term data and outcomes.

“I think we're seeing a little bit of a change in landscape, specifically because we’re realizing that maybe up to 50% of patients were not meeting these metrics,” Lammert said. “I think this has spawned and increased the pharmaceutical perspective and pursuit of other agents. We've been excited recently because now, as we all know, we had 2 FDA-approved compounds this past year that were poised to be transformative for patients who were hard to control or not meeting biochemical remission through a few different parameters.”

Elafibranor and seladelpar, both of which are peroxisome proliferator-activated receptor agonists, were granted accelerated approval for the treatment of PBC in combination with ursodeoxycholic acid in adults who have had an inadequate response to ursodeoxycholic acid, or as monotherapy in patients unable to tolerate ursodeoxycholic acid.

Lammert goes on to discuss the broader role of PPAR agonists in PBC management, noting that existing agents like bezafibrate and fenofibrate have demonstrated long-term benefits. Although these older PPAR agents have a longer track record, he says he believes the newly approved PPAR-targeting therapies may follow a similar path.

“The other PPARs, fenofibrate and bezafibrate, certainly have the leg up in terms of duration of observation and follow-up,” Lammert said. “I suspect, and I think most of us in the field think, the new PPARs will follow suit with time.”

Looking ahead, Lammert emphasizes the need for continued research to establish whether response criteria for these new agents correlate with meaningful survival improvements. He notes real-world data and long-term follow-up studies will be critical in validating their efficacy, particularly given the challenges of conducting large-scale trials once therapies are already on the market.

. June 10, 2024. Accessed March 21, 2025. 

. August 14, 2024. Accessed March 21, 2025. 

Lammert discusses the shifting landscape of treatment response metrics and the latest advancements in second-line therapy for PBC. 

Craig Lammert, MD

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