Posted January 10, 2024

Vikas Dudeja, M.D., F.A.C.S., University of Alabama at Birmingham

Pancreatitis is a painful inflammatory disease resulting from the premature activation of digestive enzymes within the pancreas, which damages the organ.¹ Pancreatitis can be acute or chronic. Each year in the United States, approximately 275,000 hospital stays are related to acute pancreatitis, and approximately 86,000 hospital stays are due to chronic pancreatitis.¹ A total of 6,471 active component Service Members received incident diagnoses of acute pancreatitis between 2004 and 2018 with women and older Service Members more likely to be affected.² Scientists do not understand what causes acute pancreatitis to shift to chronic illness. The incidence of chronic pancreatitis, or CP, increases with age. Service Members 50 years or older are four-times as likely to have CP compared to those aged 24 years or younger.²

Current options to manage or treat pancreatitis include pain medication, antibiotics for bacterial infection and surgery to remove gallstones that block pancreatic ducts. Currently, no drug therapies are available to treat the causes of acute or chronic pancreatitis, only pain management. Dr. Vikas Dudeja and his team at the University of Alabama at Birmingham hope to find a treatment option for the disease by repurposing Pirfenidone, an anti-inflammatory and anti-fibrotic drug currently approved to treat pulmonary fibrosis.

With support from a FY15 Peer Reviewed Medical Research Program Discovery Award, Dudeja and a research team at the University of Miami, Coral Gables, evaluated the effectiveness of Pirfenidone against chronic pancreatitis. The team used two animal models to explore how recurrent acute pancreatitis develops into a chronic condition. Dudeja defined recurrent acute pancreatitis as the occurrence of two or more episodes of acute pancreatitis at least three months apart, resulting in a substantially higher risk of progression to chronic pancreatitis. Dudeja and his team found Pirfenidone significantly reduced the severity of chronic pancreatitis and the progression of recurrent acute pancreatitis to CP.

The Peer Reviewed Medical Research Program also awarded Dudeja and his team a FY20 PRMRP Clinical Trial Award. This funding supports their efforts to evaluate the safety and tolerability of Pirfenidone in patients predicted to either experience moderately severe or severe acute pancreatitis. Also, the research aims to determine the ability of Pirfenidone to reduce markers of inflammation to improve patient reported outcomes. The team built in multiple, correlative studies to address knowledge gaps surrounding pancreatitis. They plan to evaluate proteomic and transcriptomic data, or information about the proteins expressed in an individual subject and how the subject’s DNA is expressed as proteins and other molecules. These data could predict the severity in which pancreatitis will progress for patients with the disease.

The team’s successful Discovery Award research led to additional PRMRP funding with a FY22 Expansion Award. With these funds, Dudeja plans to conduct a pilot clinical trial with Pirfenidone, focusing on patients with recurrent acute pancreatitis. The goals of this research stage are to evaluate Pirfenidone’s ability to reduce the recurrence of acute pancreatitis, improve quality of life measures, and improve patient-reported outcomes. They also aim to develop a predictive biomarker of the effectiveness of Pirfenidone that can be incorporated in a future clinical trial.

Congress identified pancreatitis as a Topic Area for the PRMRP for FY11, FY13-FY20, and FY22-FY23. A goal of the Congressionally Directed Medical Research Programs is to fund innovative research that offers novel and effective therapies to Service Members and their Families. If the current clinical trials for Pirfenidone as a treatment option for pancreatitis prove successful, they will be the first drug therapy treatment options for this condition.

References:

¹National Institute of Diabetes and Digestive and Kidney Diseases. 2017. Definition & Facts for Pancreatitis. https://www.niddk.nih.gov/health-information/digestive-diseases/pancreatitis/definition-facts#.

²Williams VF, Ying S, Stahlman S. 2020. Acute and Chronic Pancreatitis, Active Component, U.S. Armed Forces, 2004–2018. Medical Service Monthly Report Vol. 27 No.10. https://pubmed.ncbi.nlm.nih.gov/33112157/.

Links:

Public and Technical Abstracts: Evaluation of Pirfenidone as a Novel Therapeutic Strategy Against Recurrent Acute Pancreatitis (Expansion Award)

Public and Technical Abstracts: Evaluation of Pirfenidone as a Therapy in Patients with Predicted Moderate to Severe Acute Pancreatitis

Public and Technical Abstracts: Effect of Pirfenidone on Severity of Chronic Pancreatitis

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