Promising Results in Ulcerative Colitis Treatment
Recent Findings in the New England Journal of Medicine
A recent article in the New England Journal of Medicine has revealed encouraging results for treating Ulcerative Colitis with a drug currently approved for psoriasis. Ulcerative Colitis, a form of inflammatory bowel disease (IBD), causes long-term inflammation of the digestive tract, primarily affecting the innermost lining of the colon. This immune-mediated disorder is characterized by painful sores (ulcers) in the bowel and can lead to symptoms such as severe diarrhea, fatigue, weight loss, and abdominal pain.
Repurposing a Psoriasis Drug for Ulcerative Colitis
Ulcerative Colitis is driven by immune responses, with specific cytokines playing crucial roles in its progression. Cytokines are proteins secreted by immune cells that serve as chemical messengers, facilitating or inhibiting immune responses. Dysregulated cytokine activity can result in chronic inflammation. Researchers have developed drugs that target these cytokines to mitigate excessive inflammation. This study focused on Ustekinumab, which counteracts the inflammatory cytokines IL-12 and IL-23. Ustekinumab is already approved for other immune-mediated conditions, including psoriasis, psoriatic arthritis, and Crohn’s disease. The study’s results, published in the New England Journal of Medicine, demonstrate the drug’s potential effectiveness for Ulcerative Colitis.
The UNIFI Study: A Closer Look
The UNIFI study was a collaborative effort involving multiple investigators across the U.S., Canada, Japan, and the EU. It consisted of two treatment phases: induction and maintenance. Induction therapy is a short-term, intensive treatment aimed at reducing disease burden, while maintenance therapy involves long-term drug administration to sustain remission.
In the first phase, 961 patients from 24 medical centers were randomly assigned to one of three groups. The first group, consisting of 319 patients, received a placebo. The second group of 322 patients was administered 130 mg of Ustekinumab as induction treatment. The third group received a weight-based induction dose of Ustekinumab at 6 mg/kg. Patients responding in the first phase proceeded to receive maintenance therapy (90 mg of Ustekinumab) in the second phase. Maintenance therapy was given to 172 patients every 12 weeks, with a comparable number receiving either a placebo or Ustekinumab. Clinical parameters related to remission were assessed at 8 weeks post-induction and 44 weeks post-maintenance.
Results of Ustekinumab in Inducing Remission
Both induction therapies yielded positive results, with over 15% of patients in each treatment group achieving remission at 8 weeks, compared to only 5% in the placebo group. The second phase also demonstrated success, as 38.4% of patients receiving maintenance therapy every 12 weeks achieved clinical remission, while 43.8% of those receiving therapy every 8 weeks reached the same outcome. The study reported minimal serious adverse events among patients treated with Ustekinumab, including 2 deaths and 7 cancer diagnoses.
Approval in Europe and Future Implications
The findings from this study are highly encouraging. Many patients with Ulcerative Colitis currently rely on therapies targeting the TNF receptor pathway. However, the study’s investigators noted that nearly 50% of patients do not respond to these therapies, and many lose receptor effectiveness over time, rendering these treatments ineffective after one year. The positive outcomes from this study indicate that newer therapies like Ustekinumab could significantly enhance long-term treatment options for Ulcerative Colitis patients. Earlier this month, Ustekinumab received approval for treating Ulcerative Colitis in Europe.
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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