Newswise — According to the National Institutes of Health, between 600,000 and 900,000 Americans have ulcerative colitis, a chronic inflammatory disease of the large intestine.
While treatments for the disease exist, not all patients respond to them. The results of two global studies – one published in The New England Journal of Medicine and another in The Lancet – offer hope to these individuals in the form of two new treatments.
“For quite a while, our field has had a ‘therapeutic ceiling’ where only a percentage of patients respond to available treatments, achieve remission, and sustain control,” said , the Joseph B Kirsner Professor of Medicine at the University of Chicago and an author on both papers. “These studies describe the successful results of two new therapies that were effective in treating moderate to severe ulcerative colitis.”
paper explored the use of a drug called tulisokibart as both a treatment for the disease and a companion diagnostic to determine response to the treatment. The drug works by targeting TL1A, the product of a gene expressed in many different inflammatory cells.
The double-blind study involved two groups of patients. The first consisted of 135 adults with moderate to severe ulcerative colitis who had not responded to currently available treatments. Participants were randomly assigned tulisokibart or a placebo and followed over a 12-week period. The study found that a significantly higher percentage of participants who received the treatment (26 percent) had clinical remission compared to placebo (1 percent).
Not everyone with ulcerative colitis has the gene for TL1A, and the researchers hypothesized that the ones who do would respond better to tulisokibart. To test this hypothesis, the second group consisted of 43 people, all of whom had this gene. This group underwent the same protocols as the first. Across both groups, the researchers found that individuals who expressed the gene had a higher remission rate (32 percent) than placebo (11 percent). While the difference in this exploratory group was not statistically significant, it was enough proof to support the next phase of this therapy’s development.
“The potential to use this treatment as a companion diagnostic is an exciting advance in our field that we hope will open doors to additional pharmacogenomic approaches to predicting response to therapies,” said Rubin, who is also Chief of the Section of Gastroenterology, Hepatology and Nutrition and Director of the Inflammatory Bowel Disease Center at UChicago Medicine.
Results lead to FDA approval
Rubin served as lead and corresponding author for paper, which studied another drug called guselkumab, a monoclonal antibody that targets IL-23, the cytokine that drives many immune diseases, including ulcerative colitis. The drug, under the brand name Tremfya, has been used for many years to treat plaque psoriasis and psoriatic arthritis.
The study evaluated the efficacy and safety of guselkumab as a treatment for moderately to severely active ulcerative colitis. The double-blind study followed 701 patients over the course of 44 weeks and randomized them to either guselkumab or a placebo. The researchers found that those taking the drug had significantly greater clinical remission (23 percent) than those receiving placebo (8 percent) at 12 weeks and were more likely to maintain remission at 44 weeks (50 percent versus 19 percent). They also found that the overall safety of the drug was favorable and consistent with that found in the approved indications, and more broadly, with the class of IL-23 inhibitors previously studied.
Following the study, the FDA approved the use of Tremfya to treat moderately to severely active ulcerative colitis. In September 2024, the University of Chicago Medicine became the to administer the drug to a patient with the disease.
In a separate study published in , Rubin and Eugene B. Chang, MD, the Martin Boyer Professor of Medicine at UChicago, also partnered with researchers from the Chinese University of Hong Kong to identify gut bacterial species that are always present in people with inflammatory bowel disease. Those findings could be translated someday into a non-invasive, microbiome-based test that could diagnose IBD quickly using fecal samples from patients. This would allow doctors to intervene sooner, before the disease progresses and requires intestinal surgery.
Such advances, along with the promising results of the two clinical trials, offer hope for patients with IBD. “It’s great to have another effective option for our patients,” Rubin said.
Additional authors on the New England Journal of Medicine paper include Bruce E. Sds of Mount Sinai; Brian G. Feagan of Western University in London, Ontario; Laurent Peyrin-Biroulet, Nancy University Hospital in Vandoeuvre-les-Nancy, France; Silvio Danese of Vita-Salute San Raffaele University in Milan; Olivier Laurent, Allison Lou, Deanna D. Nguyen, Jiandong Lu, and Mark Yen of Prometheus Biosciences; Jaroslaw Leszcyszyn of Melita Medical and Radoslaw Kempenski of Wroclaw Medical University, both in Poland; Dermot P.B. McGovern and Stephan Targan of Cedars-Sinai Medical Center; Christopher Ma of the University of Calgary; and Timothy E. Ritter of GI Alliance.
The Lancet authors include Jessic R. Allegretti of Harvard University; Julian Panes of Hospital Clinic de Barcelona; Nicole Shipitofsky, Shadi S. Yarandi, Kuan-Hsiang Gary Huang, Matthew Germinaro, Rebecca Wilson, Hongyan Zhang, and Jewel Johanns of Janssen Research and Development; Tadakazu Hisamatsu of Kyorin University in Tokyo; Gary R. Lichtenstein of the University of Pennsylvania; Brian Bressler of the University of British Columbia; Axel Dignass of Goethe University in Frankfurt, Germany; and Feagan, Peyrin-Biroulet, and Sands.
Rubin has been a paid consultant of Johnson & Johnson, the maker of Tremfya.
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