The medication, icotrokinra, blocks the effects of IL-23, an immune system protein that helps drive damaging inflammation in the intestinal lining. Unlike many advanced therapies for ulcerative colitis that are given by injection or infusion, icotrokinra is taken as a pill.

An estimated 3.1 million U.S. adults have been diagnosed with ulcerative colitis, according to the Centers for Disease Control and Prevention. The chronic, debilitating condition causes inflammation and ulcers in the lining of the large intestine, leading to frequent bloody diarrhea, abdominal pain, malnutrition, anemia and joint pain.

Conducted in 21 countries, the ANTHEM-UC Phase II-B clinical trial randomly assigned participants to receive icotrokinra or a placebo. Almost half of the patients in the study had been on advanced therapies such as biologics, while the rest were on conventional anti-inflammatory medications.

“Icotrokinra was effective even in hard-to-treat patients who had failed previous drug regimens,” said Maria T. Abreu, MD, executive director of the F. Widjaja Inflammatory Bowel Disease Institute and corresponding author of the study. “The fact that the medicine can be taken orally will help us improve the range of options we have for treating patients.”

Earlier this year, the FDA approved icotrokinra for the treatment of plaque psoriasis.

“Patients with ulcerative colitis often need to try several treatments before finding one that controls their disease,” said Gil Melmed, MD, director of Inflammatory Bowel Disease Clinical Research at Cedars-Sinai. “It’s not unusual for medications that work against one immune-related condition to also benefit patients with another. We already know that targeting the IL-23 pathway can be effective in both psoriasis and inflammatory bowel disease.”

Icotrokinra demonstrated benefits at the study’s primary 12-week assessment, with patients maintaining remission through 28 weeks of treatment.

“The drug’s favorable safety profile and precise mechanism of action could make this an important addition to our treatment options for ulcerative colitis, particularly earlier in the disease,” Abreu said. “Hopefully we can study it for Crohn’s disease as well.”

Additional authors include: Britta Siegmund, MD; Lindsey Surace, MD; Ngozi Erondu, MD, PhD; Minhu Chen, MD, PhD; Karen Chachu, MD, PhD; Edouard Louis, MD, PhD; Katsuyoshi Matsuoka, MD, PhD; Jimmy Limdi, MD; Edmund Arthur, PharmD; Nicole Houck, BS; Colleen Marano, PhD; Marion L. Vetter, MD; Bin Zou, MD; Joyce Zhan, PhD; Mary Ellen Frustaci, MAS; Arun K. Kannan, PhD; Grazyna Rydzewska, MD, PhD; Edward V. Loftus Jr., MD; and Vipul Jairath, MBChB, DPhil.

Funding: The study was supported by Johnson & Johnson.

Disclosures: Maria T. Abreu, MD, reports serving as a consultant or advisory board member for AbbVie, Inc., Amgen, Bristol Myers Squibb, Genentech, Johnson & Johnson, Lilly, Pfizer Pharmaceutical, Takeda Pharmaceuticals, and UCB Pharma.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Digestive Disease Week is the largest international gathering of physicians and scientists in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

Cedars-Sinai is a nationally recognized leader in gastroenterology and gastrointestinal surgery. Digestive and liver disease experts attending the conference are available to discuss a wide variety of research, including these presentations.

Late-Breaking Trial Shows Progress in Difficult Ulcerative Colitis

Maria T. Abreu, MD, executive director of the F. Widjaja Inflammatory Bowel Disease Institute, will present late-breaking results from a clinical trial evaluating two targeted biologic therapies for ulcerative colitis used together. The study focused on patients whose disease had not responded to multiple advanced treatments and found that the combination led to higher rates of clinical remission and healing of the intestinal lining compared with either drug alone.

“We studied patients whose disease has already proven difficult to treat and found that using two therapies together led to stronger outcomes than either alone, without increasing side effects,” Abreu said.

Irritable Bowel Syndrome (IBS)

Ali Rezaie, MD, medical director of the GI Motility Program, will present research that found palatable elemental diet nutrition replacement reduced abdominal pain and related symptoms in people with irritable bowel syndrome after two weeks.

Zoe Krut, MHDS, a clinical research coordinator with the Center for Outcomes Research and Education at Cedars-Sinai Health Sciences University, will present research from a multicenter randomized trial showing that virtual reality-delivered cognitive behavioral therapy improved symptoms of IBS and was well accepted by patients. Study leader Christopher Almario, MD, MSHPM, assistant professor of Medicine and Health Systems Research, will also be on hand to discuss the research.

Interventional Gastroenterology

Barham K. Abu Dayyeh, MD, MPH, director of Interventional Gastroenterology, will share results of a study in which a less invasive laparoscopic procedure for hiatal hernia-associated GERD (gastroesophageal reflux disease) was used. It achieved results similar to standard surgery, with fewer complications. The abstract has been selected for the “Best of DDW” session held at the end of the meeting, highlighting 6 of the top studies presented.

Abu Dayyeh will also share results of another study in which a novel endoscopic therapy used pulsed electric fields to treat the lining of the small intestine. Results reveal improvements in blood sugar control and weight management for nearly one year in adults with Type 2 diabetes.

Inflammatory Bowel Disease

Talin Haritunians, PhD, a research associate professor of Medicine, will present results of a study that found patients with inflammatory bowel disease (IBD) have distinct genetic variants linked to an increased risk for cardiovascular disease, independent of traditional risk factors.

Allistair Clark, MA, a clinical research data specialist at Cedars-Sinai Health Sciences University, will share results of an investigation that found an AI-powered virtual reality therapy reduced pain and anxiety in patients with inflammatory bowel disease (IBD) in both inpatient and outpatient settings.

Small Intestinal Bacterial Overgrowth (SIBO)

Ruchi Mathur, MD, an endocrinologist, and Gabriela Leite, PhD, a research scientist, will present research linking changes in the small bowel microbiome to Type 2 diabetes. These include strong associations with small intestinal bacterial overgrowth (SIBO) and higher glucose levels. Mathur and Leite are with the Medically Associated Science and Technology (MAST) Program.

Diagnostics: Breath Testing

Mark Pimentel, MD, gastroenterologist, and project scientist Maria Jesus Villanueva-Millan, PhD, of the MAST program, are available to discuss their research t directly comparing breath and small-intestine gases in the same patients, showing that hydrogen sulfide levels reflect those in the small intestine and are linked to specific microbes and diarrhea severity.

Liver Disease

Hyunseok Kim, MD, MPH, PhD, hepatologist and assistant professor, Medicine, will present results of research examining biomarkers that may help predict cirrhosis and liver disease progression in people with alcohol-associated liver disease.

Ju Dong Yang, MD, medical director of the Liver Cancer Program, and clinical research data specialist Osama Khattab, MD, are available to discuss their research showing that transarterial radioembolization (TARE) achieved survival outcomes comparable to ablation in early-stage liver cancer, suggesting it may offer an alternative treatment option for patients.

Media Contact

To schedule an interview with a Cedars-Sinai expert during the conference, please contact Laura Coverson Laura.Coverson@cshs.org or 310-562-1112.

Ulcerative colitis is a type of inflammatory bowel disease (IBD) that causes chronic inflammation and sores in the colon.

“Ulcerative colitis greatly increases a person’s risk of developing colorectal cancer, but we don’t have a noninvasive way to determine how great each patient’s risk might be,” said Hajar Hazime, PhD, a project scientist in the Abreu Lab at Cedars-Sinai and co-first author of the study. “Undergoing frequent surveillance colonoscopies can help, but preparing for that procedure is especially difficult for someone with ulcerative colitis.”

Additionally, colonoscopy results can be inconclusive, forcing the physician and patient to decide whether to remove all or part of the colon to prevent cancer from developing, Hazime said. Investigators hoped to find a more conclusive and less invasive way to screen these patients.

“Our physician-scientists are continually working to improve cancer screening for our patients,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “We treat more than 60 types of cancer, but our ultimate goal is prevention.”

Each person’s gut is populated with trillions of microbes—bacteria, viruses, fungi and other organisms too small to see with the naked eye. These interact with each other and appear to influence several aspects of a person’s health, including IBD.

Hazime said that these microbes use QSMs to communicate and coordinate their behavior, and that a goal of the study was to determine whether QSMs play a role in causing colon cancer in patients with ulcerative colitis.

When the investigators examined blood samples from human patients with ulcerative colitis and conducted experiments using colon organoids and laboratory mice, they found:

• In the blood of ulcerative colitis patients, there were higher levels of QSMs in patients at higher risk for cancer, who had experienced symptoms for 10 years or longer, than in patients at lower cancer risk, with symptoms for five years or less.
• In colon organoids—tiny clusters of cells that mimic some functions of the human colon—exposure to QSMs caused inflammation, which is a risk factor for tumor development. Because organoids do not contain gut microbes, this showed that elevated QSM levels and the activity of microbes they regulate can increase cancer risk.
• In laboratory mice with a condition that mirrors ulcerative colitis, investigators found higher levels of QSMs in the blood of those that developed tumors than in those that did not. Also, mice exposed to extra levels of QSMs developed more tumors, more quickly, than those not exposed.

“These results show us that quorum sensing molecules are not only associated with colon cancer risk in patients with ulcerative colitis, but that they actually contribute to the formation of these tumors,” said Maria T. Abreu, MD, executive director of the F. Widjaja Inflammatory Bowel Disease Institute and co-corresponding author of the study. “That makes these molecules a potential way to screen patients for cancer risk, but also a possible target for reducing risk.”

Investigators will next focus on pinpointing how QSMs contribute to tumor formation, studying the molecules as a biomarker to predict cancer development, and finding ways to target these molecules to disrupt cancer development, Abreu said.

Additional Cedars-Sinai authors include Irina Fernández, Katerina M. Faust, and Maria A. Quintero.

Other authors include Gregory O’Connor, Juan F. Burgueño, Ana M. Santander, Nivis Brito, Yuguang Ban, Sapna K. Deo, and Sylvia Daunert.

Funding: This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099076) and the Micky & Madeleine Arison Family Foundation Crohn's & Colitis Discovery Laboratory to MTA as well as from the National Institutes of Health (R01GM127706) and the Department of Defense (W81XWH-20-1-0697) to SD and SKD and the Lucille P. Markey Chair in Biochemistry and Molecular Biology to SD.

Disclosures: MTA is a consultant or on the advisory board of the following companies: AbbVie Inc., Alimentiv Inc., Amgen, Bristol Myers Squibb, Eli Lilly and Company, Genetech, Gilead Sciences, Janssen Pharmaceuticals, Pfizer Pharmaceutical, Takeda Pharmaceuticals, and UCB Pharma.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.