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.

The IBD Prehabilitation Program, pioneered at Cedars-Sinai, has significantly enhanced surgical outcomes and reduced complications for patients with the digestive disease.

Gil Melmed, MD, director of Inflammatory Bowel Disease Clinical Research, led the development of the multidisciplinary program and is eager to study its effectiveness in healthcare systems serving patient populations where English is not the primary language.

“We don’t know if the positive outcomes from the program are specific to our local environment and patient population or if they also have wider application,” Melmed said. “This generous grant from the Helmsley Charitable Trust enables us to expand the IBD prehabilitation protocols to a completely different environment and to patient populations in an international setting.”

Cedars-Sinai will partner with Sheba Medical Center through its ARC innovation center, along with two additional Israeli hospitals, to establish prehabilitation programs for IBD patients in need of surgery.

The 10-week program involves comprehensive care starting a month before surgery. Patients receive tailored dietary, mental health and physical therapy interventions both before and after their procedures.

“We have found that people participating in the program experienced a significant reduction in complications after surgery, as well as a reduction in 30-day readmissions and repeated surgery. They also required less opioid medication for pain,” said Melmed, who is also the associate director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai.

An estimated 3 million people in the U.S. have inflammatory bowel disease, according to the Centers for Disease Control and Prevention. Worldwide, the Crohn’s & Colitis Foundation estimates that about 10 million people are living with IBD. The disorder produces chronic and often destructive inflammation in the digestive tract. The two most common forms of IBD are Crohn’s disease and ulcerative colitis, with Crohn’s disease patients generally requiring abdominal surgery at least once in their lifetime.

“As part of the grant, we will develop patient materials in multiple languages, including English, Spanish, Arabic and Hebrew. If successful, we hope to expand to other countries to share this approach to meaningful improvement in health outcomes for people who require surgery to manage their disease,” Melmed said.

In 2022, the Helmsley Charitable Trust awarded Cedars-Sinai $1.25 million for initial development of the IBD prehabilitation program aimed at optimizing care and improving surgical outcomes and the overall health of patients undergoing major abdominal surgery.

Read more from Cedars-Sinai Stories and Insights: Is It IBS or IBD?

Melmed told Everyday Health a gastroenterologist who specializes in inflammatory bowel diseases can provide expert treatment for ulcerative colitis. They also can perform colonoscopies, “a very important tool for understanding, evaluating and assessing the state of colitis, which enables treatment decisions,” he said.

Melmed told Everyday Health that a primary care physician can recommend a gastroenterologist and that patients may want to do some research to find out the specialist’s experience treating the disease.

Because up to 30% of people with ulcerative colitis may need surgery to control their symptoms, Melmed said making a plan early on, just in case—such as finding a surgeon and medical center that specialize in bowel diseases and that are included in the patient’s insurance network—is important.

Melmed told Everyday Health patients should bring their medical records, including colonoscopy reports, imaging and medication history, to their first visit with a new physician.

“It can be tricky for a doctor to see new patients when the records aren’t available,” he said.

It also may be helpful to bring a list of questions to that first appointment, as well as a health history summary and a journal detailing symptoms.

Click here to read the complete article from Everyday Health.

The findings of the single center randomized controlled trial are published in Scientific Reports.

“We found that Cedars-Sinai patients in the P.A.I.N.-Sparing group received significantly less opioids and had greater physical activity during their hospitalization, when compared with IBD patients whose pain was treated with as-needed opioids. Also, those receiving the P.A.I.N. protocol tended to have lower overall pain scores while in the hospital,” said Gil Melmed, MD, principal investigator of the study and director of Inflammatory Bowel Disease Clinical Research at Cedars-Sinai.

The P.A.I.N.-Sparing treatment approach developed by investigators was based on a review of the literature on pain management and included scheduled, non-opioid pain medications tailored to the severity of a patient’s reported discomfort. Melmed said that if this approach were not sufficient to control pain, the IBD patients could request opioid pain medications, as needed.

Inflammation, severe diarrhea, malnutrition and acute and chronic pain are leading causes of repeat hospitalizations for IBD patients. Pain is rated by these patients as one of the most burdensome aspects of the disease, yet there is insufficient evidence to support a pain management strategy that is effective.

“Opioid use is more prevalent in IBD than in any other chronic gastrointestinal condition. In spite of the widespread use of these medications, our previous studies have found that opioids do not meaningfully reduce the pain these patients experience. Additionally, there are the known risks associated with using these medications for chronic conditions, including misuse, overdose, infection, hospital readmission and even death,” said Melmed, a professor of Medicine.

Larger, multicenter trials would be useful to further validate the efficacy of the P.A.I.N.-Sparing protocol for IBD patients, Melmed said. He is also encouraged by the emergence of new tools for managing pain.

“There are novel, non-pharmacologic strategies being rigorously studied for their potential to control acute and chronic pain. Biofeedback, virtual reality and other modalities could be incorporated into a proactive approach for addressing the pain and quality of care of our hospitalized IBD patients,” Melmed said.

Additional (current) Cedars-Sinai investigators: Devin Patel, MD; Rajalakshmi Govalan, MD; Shao-Chi Greg Huang; Catherine Bresee; and Teryl K. Nuckols, MD.

Follow Cedars-Sinai Academic Medicine on X for more on the latest basic science and clinical research from Cedars-Sinai. 

The findings are published in the journal Gastroenterology.

“Even though biologic medications have significantly improved outcomes for our patients with Crohn’s disease or ulcerative colitis, some people do not respond well to these therapies. In our study, we found that the patients with higher amounts of internal abdominal fat were less likely to improve and experience remission from their disease,” said gastroenterologist Andres J. Yarur, MD, the corresponding author of the study.

Unlike some conventional anti-inflammatory drugs which treat inflammation in a non-selective way, biologics work by blocking specific targets that cause inflammation in the body.

Patients in the study with higher visceral fat levels had lower concentrations of the biologic medications in their blood after treatment, and lower rates of steroid-free remission and bowel healing.

“It may not be body weight or body mass index [BMI] that is the reason some of our patients benefit from these approved biologic medications. It seems the fat tissue on the inner side of the abdomen, in particular, impacts treatment, so we may need to use higher doses of the drugs to help these patients,” said Gil Melmed, MD, a co-author of the study and director of Inflammatory Bowel Disease Clinical Research at Cedars-Sinai.

Investigators treated 141 IBD patients with one of three biologic medications: infliximab, ustekinumab or vedolizumab. Reliable body composition measurements were taken for both the IBD group and the 51 healthy control subjects to ensure fat composition for the two groups were similar.

“We found that higher visceral adiposity was associated with higher levels of pro-inflammatory cytokines, suggesting that fat tissue promotes inflammation, the opposite of what we want, and increases resistance to biologic drug therapy. More research is needed because we don’t know whether lowering visceral fat or giving higher doses of the medications would improve drug efficacy,” said Melmed.

Yarur, the study’s principal investigator, agrees, adding that a different kind of medication may be more effective in patients with a high intra-abdominal visceral fat. 

“We need to investigate drugs with different mechanisms of action, especially other small molecules, to see if our findings hold. As the prevalence of obesity and metabolic syndrome increases in our population, we need to find interventions that would improve the body composition of these IBD patients who are not currently helped by these biologic treatments,” said Yarur.

DOI: https://doi.org/10.1053/j.gastro.2023.06.036

Funding: The pilot study for this investigation was funded by a grant from the Digestive Disease Center at the Medical College of Wisconsin.

Conflicts of Interest:  Andres Yarur is a consultant, and member of the advisory board, for Takeda, which manufactures vedolizumab, and for Celltrion Healthcare, which produces one biosimilar of infliximab. Gil Melmed is also a consultant to Takeda and Janssen Immunology, the makers of infliximab and ustekinumab.

Follow Cedars-Sinai Academic Medicine on Twitter for more on the latest basic science and clinical research from Cedars-Sinai.

Read more on Discoveries Magazine: Ancestry Matters: Genetic Risk Factors for IBD