Research Spotlight: Tofacitinib Is Effective in Treating Refractory Immune Checkpoint Inhibitor Hepatitis

Michael Dougan, MD, PhD, a physician investigator in the Division of Gastroenterology at Massachusetts General Hospital and an associate professor of Medicine at Harvard Medical School, and Ryan Sullivan, MD, a physician investigator at the Mass General Cancer Center and an associate professor of Medicine at Harvard Medical School are co-senior authors of a new study in Clinical Gastroenterology and Hepatology, Tofacitinib Is Effective in Treating Refractory Immune Checkpoint Inhibitor Hepatitis. 

Additional Mass General Brigham authors include Kerry Reynolds, MD, Kamaneh Montazeri, MD, Esperance Schaefer, MD, MPH, and Mike Wang, MD. 

What was the question you set out to answer with this study?

Metastatic melanoma occurs when this form of skin cancer spreads to other parts of the human body. The most effective method of treating metastatic melanoma is immune checkpoint inhibitors (ICIs).  

These treatments have improved metastatic melanoma outcomes, however, toxicities resulting from treatment, such as hepatitis, can be dose-limiting or even fatal. Sometimes these toxicities do not respond to our standard therapies and in those situations, we do not have a good idea about what is best to try next, 

Therefore, our team decided to investigate whether tofacitinib, a Janus kinase (JAK) inhibitor, could have efficacy in severe hepatitis caused by ICIs that did not respond to our standard therapy.  

What Methods or Approach Did You Use?

To investigate the efficacy of tofacitinib, we used a case series study of three patients.  

These patients represent consecutive patients referred to the Massachusetts General Hospital Severe Immunotherapy Complications (SIC) service who were determined by our experts to have treatment failure with other treatments such as systemic glucocorticoid and antimetabolite combination therapy between August 2022 and September 2023. 
 
These were the only three patients managed by the SIC service who were treated with tofacitinib for ICI hepatitis during that time.  

What Did You Find?

In the three patients we treated with tofacitinib, all of them responded rapidly. We found that the medication might be able to reverse severe damage to the liver that is caused by cancer immunotherapy. Also of note, while we did find that tofacitinib was successful for hepatitis, the oncologic outcomes of each of the three patients varied. 

What are the Implications?

Because of these findings, we can provide a much-needed potential therapy for patients with a life-threatening, refractory toxicity from immunotherapy.  

What are the Next Steps?

While the results from this case series are important, the next steps are to perform a larger, prospective, and ideally randomized clinical trial to confirm the potential benefits of tofacitinib for patients.   

Additional studies are also needed to ascertain which populations will benefit most from JAK inhibition while maintaining durable responses to their cancers. 

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.