A recent article published in the New England Journal of Medicine has shown extremely promising results for the treatment of Ulcerative colitis using a drug that is currently approved for the treatment of Psoriasis.
Ulcerative Colitis is a form of inflammatory bowel disease (IBD) that causes long-term inflammation of the digestive tract. This immune-mediated disorder affects the innermost lining of the colon and is characterized by the development of painful sores (ulcers) in the bowel. This can manifest into many different symptoms such as severe diarrhea, fatigue, weight loss, and abdominal pain.
Repurposing a Psoriasis drug for the treatment of Ulcerative colitis
Ulcerative colitis is an immune-mediated disease, and certain cytokines are critical for its progression. Cytokines are proteins that are secreted by immune cells and act as chemical messengers, either activating or blocking specific immune responses. Uncontrolled secretion or activity of cytokines can lead to chronic inflammation. Based on the knowledge of the structure of cytokines, scientists have devised drugs that can bind and block the undesirable action of cytokines, including chronic inflammation. This study evaluated the effect of drug Ustekinumab, which acts by counteracting the actions of inflammatory cytokines IL-12 and IL-23. The drug has been approved for the treatment of other immune-mediated conditions – psoriasis, psoriatic arthritis, and Crohn’s disease. The results of the study were published in the New England Journal of Medicine and highlight some really exciting results showing the efficacy of this drug in the treatment of Ulcerative Colitis.
The UNIFI study – treating ulcerative colitis with Ustekinumab
The trial, which is called the UNIFI study was a collaborative effort from multiple investigators across the U.S., Canada, Japan, and the EU. The study involved two phases of treatment – an induction treatment and maintenance treatment. Induction therapy is a stronger and short-term treatment aimed to reduce the overall burden of disease, while maintenance therapy involves the long-term administration of the drug to ensure remission. During the first phase, 961 patients from 24 medical centers were randomly assigned to one of three groups. The first group of 319 patients received a placebo (no drug) whereas 322 patients in the second group received an induction treatment of 130 mg. The third group received induction treatment based on weight and were administered Ustekinumab at 6 mg/kg. The patients who responded in the first phase of the study were selected to received maintenance therapy (90 mg of Ustekinumab) in the second phase of the study. Maintenance therapy was given to 172 patients every 12 weeks, while approximately the same number of patients received either a placebo or Ustekinumab. Various clinical parameters that correlate with remission (absence of disease) were assessed at 8 weeks after induction therapy and 44 weeks after the maintenance therapy.
Ustekinumab induced remission in patients with ulcerative colitis
Both kinds of induction therapies were successful with greater than 15% of patients in each arm of the intervention showing remission at 8 weeks in comparison to 5% of patients in the placebo group. The second phase of the study was also successful with 38.4% of patients receiving maintenance therapy every 12 weeks exhibiting clinical remission. Similarly, 43.8% of patients who received maintenance therapy every 8 weeks showed clinical remission. There were few serious adverse events (side effects) among patients who received Ustekinumab (2 deaths and 7 cancer diagnoses).
Approved in Europe to treat ulcerative colitis
The results of this study are very encouraging. Many ulcerative colitis patients are given therapies that act on TNF receptor pathway. However, investigators of the study noted that almost 50% of patients do not respond to such therapies and many patients lose the receptor over time, making these therapies ineffective after one year. Therefore, positive results from this study suggest that newer drugs like Ustekinumab could be beneficial in expanding long-term treatment options for Ulcerative colitis patients. Earlier this month the drug was approved for the treatment of Ulcerative colitis in Europe.
Written by Vinayak Khattar, Ph.D., M.B.A
References:
- Sands, Bruce E., et al. “Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis.” New England Journal of Medicine, vol. 381, no. 13, Sept. 2019
- “Ulcerative Colitis – Symptoms and Causes.” Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/symptoms-causes/syc-20353326. Accessed 27 Sept. 2019.
- Kaplan, Gilaad G., et al. “The Impact of Inflammatory Bowel Disease in Canada 2018: Epidemiology.” Journal of the Canadian Association of Gastroenterology, vol. 2, no. Supplement_1, Feb. 2019, pp. S6–16. academic.oup.com, doi:10.1093/jcag/gwy054.
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