Ulcerative Colitis Research

Disease research includes basic research and clinical research. In ulcerative colitis, basic research is done to understand how genes, microorganisms, and the immune system work together in a person with the disease. Basic research often takes place in a laboratory. Clinical research involves people. Clinical research studies are done to determine whether a treatment is safe and effective in humans. Clinical research studies are conducted in steps, called phases.

Current ulcerative colitis research questions include:

  • Why is it that a medication works very well for some people and not others?
  • How can we make it easier to take medications for ulcerative colitis?
  • Can we develop medications with fewer side effects?
  • Can we make medications more affordable?

Medications called “anti-tumor necrosis factor” (anti-TNF) agents help many people manage their disease. However, there are a number of people who do not respond to this kind of medication.1 Furthermore, some people get better after starting anti-TNF therapy, but the medication eventually stops working.

Ulcerative colitis is different for each person, because each person’s immune system is unique.2 Researchers are trying to understand what causes the variations in immune response. This information may lead to the discovery of more effective medications.

Future medications may have fewer side effects because they are better at targeting just one cell type or immune process. It may also become possible to take some biologic medications by mouth. (Currently available biologics must be injected or infused.) Below are a few medications in development for ulcerative colitis.

Investigational Medications

Tofactininb (brand: Xeljanz). Tofacitinib is currently approved for the treatment of rheumatoid arthritis. It is also being studied in Phase III trials for moderate-to-severe ulcerative colitis. Phase III trials are done with a large group of people. The goal of the trial is to confirm that the drug works and to see how frequently side effects occur. Phase III trials are usually the last step before the Food and Drug Administration (FDA) decides whether to approve the medication for a certain use.

In the Phase III trials, tofacitinib is being compared with fake treatment (placebo). Early results show that more people treated with tofacitinib achieved remission at 8 weeks compared with people who received the placebo treatment.3

Tofacitinib is a medication called a JAK inhibitor.4 It blocks cytokine signaling pathways from inside the cell. Cytokines are proteins that control the level of inflammation. Blocking their signals infers with inflammation. Tofacitinib is taken by mouth.

Ozanimod. This medication is currently being studied in Phase III trials. It works by interfering with signals from a receptor called “S1P” (sphingosine 1-phosphate). This action seems to prevent white blood cells from traveling to inflamed areas in the body. Ozanimod was studied in a Phase II study with people who have moderate to severe ulcerative colitis.5 People who received ozanimod were more likely to be in remission after 8 weeks of treatment than people who received the placebo treatment. Symptoms and damage to the lining of the intestine also improved. More of the people treated with ozanimod remained in remission at 32 weeks, too. Ozanimod is taken by mouth.

Cobitolimod (brand: Kappaproct). Phase IIb tests of this medication will be starting.6 Cobitolimod is administered as two rectal doses given 4 weeks apart. It reduces inflammation in the colon. This helps the lining of the intestinal tract to heal. It also improves symptoms such as blood in stool and number of stools. Its target is a cell receptor called “TLR9” (toll like receptor 9).

AVX-470. This medication is in Phase I testing, which is a very early stage.7 It is a biologic medication that blocks tumor necrosis factor (TNF). Blocking TNF proteins interrupts the inflammatory process. Unlike approved anti-TNF medications (examples: infliximab, adalimumab, certolizumab pegol, and golimumab), AVX-470 can be taken by mouth. In the Phase I study, AVX-470 was safe and well tolerated.7 The study was not designed to test whether it was effective.

CT-P13 (biosimilar infliximab). Biologic medications are complex medications that are engineered from living cells. Because of the difficulty of developing and manufacturing biologics, these medications are very expensive.

For conventional medications, generics are exact copies of the branded product that cost far less.8 However, it is impossible to copy a biologic medication exactly because they are produced by living cells. There cannot be a “generic” biologic. Instead, the FDA is allowed to approve a medication that is “highly similar” to a biologic medication, which is called a biosimilar. The manufacturer of a biosimilar must show that there are no clinically meaningful differences between the biosimilar and the original biologic.

CT-P13 is an infliximab biosimilar. In February 2016, an FDA advisory committee voted to support CT-P13.9 If it is approved, CT-P13 may be a lower cost option for treating ulcerative colitis and Crohn’s disease.

Participating in a Clinical Trial

You may be interested in participating in a clinical trial of treatment for inflammatory bowel disease. By participating, you may have access to investigational treatments, such as new medications or innovative surgery.

High-quality trials involve oversight and safety procedures to protect participants; however, all research has inherent risks. ClinicalTrials.gov includes a list of questions to ask before participating in any trial, including:10

  • What are you studying?
  • Why do you think that this intervention might be effective?
  • What are the possible interventions that I might receive during the trial?
  • What are the possible risks, side effects, and benefits of the intervention being studied? How do they compare with those of my current treatment?
  • What will I have to do as part of this study?
  • How long will this study last?

You can find information about ongoing inflammatory bowel disease trials at:

Written by: Anna Nicholson | Last Reviewed: January 2016.
View References
  1. Löwenberg M, D'Haens G. Next-generation therapeutics for IBD. Curr Gastroenterol Rep. 2015;17:444.
  2. CCFA. The Immune Response and IBD [video]. Published March 7, 2016. Accessed April 5, 2016 at: https://www.youtube.com/watch?v=GPmqSEsUVL0
  3. Pfizer announces positive top-line results from two phase 3 trials of oral tofacitinib in adults with moderate-to-severe ulcerative colitis [press release]. September 21, 2015. Accessed April 5, 2016 at: http://on.pfizer.com/1V6XPcW.
  4. Xeljanz® [package insert]. New York, NY: Pfizer Inc; 2016.
  5. Phase 2 maintenance data from oral ozanimod TOUCHSTONE study in ulcerative colitis presented at ACG plenary session [press release]. October 19, 2015. Accessed April 5, 2016 at: http://bit.ly/1YegLDJ
  6. InDex Pharmaceuticals receives FDA clearance of IND for cobitolimod (Kappaproct®) Phase IIb trial [press release]. March 7, 2016. Accessed April 5, 2016 at: http://bit.ly/1N7JO6e.
  7. Harris MS, Hartman D, Lemos BR, et al. AVX-470, an orally delivered anti-tumour necrosis factor antibody for treatment of active ulcerative colitis: Results of a first-in-human trial. J Crohns Colitis. 2016 Jan 28. [Epub ahead of print.]
  8. US Food and Drug Administration. Information for consumers (biosimilars). Accessed April 5, 2016 at: http://1.usa.gov/1rvPtuj.
  9. Ault A. FDA advisers back infliximab biosimilar CT-P13. Medscape Medical News. February 10, 2016. Accessed April 5, 2016 at http://www.medscape.com/viewarticle/858749.
  10. ClinicalTrials.gov. Learn about clinical studies. Accessed April 5, 2016 at: http://1.usa.gov/1qu60Tl.