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.

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Author | Jina Sawani

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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.

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"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."

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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
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