DAY 2 - Upadacitinib Passes Real-World Test in the Treatment of Acute Severe Ulcerative Colitis

An analysis featured at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania showed that patients treated with upadacitinib for acute severe ulcerative colitis (UC) achieve similar outcomes to those of infliximab users, and may also experience lower rates of severe complications such as colonic perforation.

Upadacitinib (Rinvoq), a selective Janus kinase 1 inhibitor, has emerged as a novel, promising therapy for moderate to severe UC. The U.S. Food and Drug Administration approved upadacitinib for this indication in early 2022, after phase 3 clinical studies confirmed its efficacy and safety in patients with UC. In the current clinical landscape, this agent can be considered as a second-line therapy for the treatment of adults with moderately to severely active UC who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.

A research team at the University of Pennsylvania Medical Center, in Philadelphia, designed a retrospective cohort study to evaluate the real-world efficacy and safety outcomes of upadacitinib and compare them to those of infliximab use in hospitalized patients with acute severe UC. Lead author Tushar Khanna, MD and his collaborators at the Mayo Clinic in Jacksonville, Florida and the Case Western Medical Center in Cleveland, Ohio used data from the TriNetX platform, which included the records of 130 million patients treated across 64 healthcare organizations. The authors identified nearly 3,500 patients hospitalized for acute severe UC who were treated with infliximab and 180 patients treated with upadacitinib for the same indication. After propensity score matching was used to balance baseline characteristics, including age, gender, race, laboratory values, and comorbidities between the cohorts, each treatment group included 177 patients who were followed up over a 5-year period after exposure to therapy.

When looking at prior therapies, the authors noted that a greater proportion of patients in the upadacitinib group were previously treated with adalimumab (20.3%) and ustekinumab (25.4%) compared with those in the infliximab group. Moreover, nearly half (44.1%) of the people who received upadacitinib had previous exposure to infliximab. While the analysis was not designed to pinpoint the timeline of therapy switches or identify the reasons behind them, patients with prior infliximab exposure likely had experienced loss of response to this therapy or had been treated with TNF inhibitors prior to presenting to the hospital, Khanna explained.

“I would imagine that patients who had been on infliximab are a special cohort who tend to be sicker and are nonresponsive to the standard of care,” Khanna said in an interview. “We see that, even in those patients, the complication rates are no higher [than in the other cohort].” The analysis did not detect significant differences in colectomy rates between the two treatment groups. Furthermore, no significant differences were found regarding future steroid use or other complications, including rectal bleeding, rates of blood transfusion, and infections. Adverse events and incident mortality rates were also comparable between the groups.

“This is really a non-inferiority study for patients who had already been exposed to anti-TNFs, showing they can safely be given upadacitinib,” Khanna clarified. “Upadacitinib demonstrates comparable efficacy and safety to infliximab in real-world hospitalized UC patients. While there was no significant difference observed with regard to colectomy rates, it was interesting to note a decreased rate of colonic perforation in the upadacitinib group compared to infliximab. These findings support the use of upadacitinib as a viable alternative to infliximab for UC treatment, with consideration for individualized patient risk factors.”

As the data about novel second-line therapies for UC continue to evolve, future studies may shed light on the reasons behind therapeutic switches as well as the long-term effects of previous exposure to different therapies in patients treated with upadacitinib.