Tofacitinib for severe ulcerative colitis: Will it prevent colectomies?

Gastrointestinal experts explore the benefits of the drug when treating patients with acute severe ulcerative colitis.

5:00 AM

Author | Jina Sawani

Image of colitis on black background
Getty Images

Acute severe ulcerative colitis, or ASUC, can be extremely debilitating. Symptoms for the condition range from frequent bloody bowel movements to anemia, weight loss, and even fevers and chills. And nearly 30% of individuals who develop an episode of ASUC require a colectomy, which is a surgery that involves removing parts, or all, of your colon.

"When someone with ASUC has a colectomy, it's irreversible and certainly can have a huge impact on the quality of their life," said Jeffrey Berinstein, M.D., a gastroenterologist and clinical lecturer at Michigan Medicine. "Janus kinase inhibitors, which are better known as JAK inhibitors, are drugs that work to inhibit the activity of certain enzymes. The JAK inhibitor, tofacitinib, has shown itself to be an effective drug when treating ASUC. But I teamed up with several of my colleagues, including Peter Higgins, M.D., Ph.D., to truly examine if its use could prevent individuals from having this life-altering surgery."

The team's research on tofacitinib was recently published in Clinical Gastroenterology and Hepatology.

According to Berinstein, ASUC is considered a medical emergency and requires treatment quite quickly.

Like Podcasts? Add the Michigan Medicine News Break on iTunes or anywhere you listen to podcasts.

"Nearly 20 to 30% of patients with ASUC will be hospitalized with an acute flare in their lifetime," said Berinstein. "There is a critical unmet need for additional therapeutic options for patients that are hospitalized with this condition, especially among individuals who have already failed to respond to a medication beforehand."  

He also said that despite significant advances in treatment options for patients with ulcerative colitis, the current medical management of the sickest individuals with this condition remains unacceptable.

"Close to 30% of patients with ASUC require an unplanned colectomy within 90 days of being hospitalized. This is very alarming."

Studying tofacitinib in treatment of acute severe ulcerative colitis

The team examined two groups of patients with ASUC who previously failed to respond to a biologic medication (like infliximab). The first group received standard care, which involved intravenous corticosteroids, as well as a rescue dose of infliximab or cyclosporine, as needed.

The second group received tofacitinib, in addition to corticosteroids. The tofacitinib group was stratified according to dosage to determine if an off-label and high-intensity 10 milligram dose administered three times a day was more effective than the approved dose of 10 milligrams administered two times a day.

"We found that tofacitinib reduced the rate of colectomy in patients admitted with ASUC compared to the control group," said Berinstein. "But the reduction in colectomies was driven entirely by the 10 milligram dose of tofacitinib administered three times a day. Notably, we saw no benefits among the patients who only received the drug twice daily, even when compared to steroid use alone."

MORE FROM THE LAB: Subscribe to our weekly newsletter

In addition, the team was surprised to find that there were not any post-operative complications in the tofacitinib group when compared to the control group. While the difference was not significant, Berinstein noted that their study was not designed around observing safety measures.

"However, this observation supported our hypothesis that tofacitinib is rapidly cleared from an individual's system (due to a short half-life) and is gone by the time an urgent colectomy may be needed," he said. "When looking to the future, we hope to conduct a larger multi-center study to see if our findings are reproducible. But I'd be remiss not to mention that we're very encouraged by these findings."

Higgins added that ultimately, this study may provide a path forward for the rapid treatment of flares and reducing colectomies among this patient population: "We hope to get this funded and up and running soon."

Paper cited: "Tofacitinib for Biologic-Experienced Hospitalized Patients with Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study," Clinical Gastroenterology and Hepatology. DOI: 10.1016/j.cgh.2021.05.038

More Articles About: Lab Report Crohn's and Colitis All Research Topics Digestive (GI) Conditions
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of healthcare news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]


Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Featured News & Stories woman holding stomach pain mustard colored shirt jeans sitting on couch
Health Lab
Can coordinated care help patients with high-risk IBD?
A team looks at how a more intentional approach to care can benefit individuals with the gastroenterological condition.
Illustration of scientists and doctors playing basketball in white coats and scrubs
News Release
Four U-M teams selected for virtual tournament of science
U-M researchers' work made the bracket in the 2024 STAT Madness tournament of science, and need public support to advance
Older woman checks her face in the mirror
Health Lab
Does trying to look younger reduce how much ageism older adults face?
How do ageism and positive age-related experiences differ for people who have tried to look younger, or feel they look younger, than they actually are? A new study examines this and the relationship with health
Jianping Fu, Ph.D., Professor of Mechanical Engineering at the University of Michigan and the corresponding author of the paper being published at Nature discusses his team’s work in their lab with Jeyoon Bok, Ph.D. candidate at the Department of Mechanical Engineering.
Health Lab
Human stem cells coaxed to mimic the very early central nervous system
The first organized stem cell culture model that resembles all three sections of the embryonic brain and spinal cord could shed light on developmental brain diseases
Graphic showing pills, a heart and brain with data on aspirin use
Health Lab
Aspirin can prevent a second heart attack or stroke, but many don’t use it
Washington University School of Medicine and Michigan Medicine researchers found that fewer than half of people who have experienced a heart attack or stroke use aspirin to prevent a second one.
Minding Memory with a microphone and a shadow of a microphone on a blue background
Minding Memory
Racial Disparities in Alzheimer’s Disease and Related Dementias
In this episode of Minding Memory, Matt & Donovan speak with Dr. Lisa Barnes, the Alla V. and Solomon Jesmer Professor of Gerontology and Geriatric Medicine, Department of Neurological Sciences and Associate-Director of the Rush Alzheimer’s Disease Center at Rush University. Dr. Barnes talks with Matt & Donovan about racial disparities in Alzheimer’s disease dementia and several obstacles that have impeded our understanding of race and dementia.