To continue with topic of new medications for ulcerative colitis started yesterday -two more articles:
- WJ Sandborn et al. Gastroenterol 2020; 158: 537-49
- S Danese. Gastroenterol 2020; 158: 467-70 (commentary)
The first reference describes a randomized phase 2 study of mirikizumab with 249 patients. Mirikizumab is a monoclonal antibody to the p19 subunit of IL23. A similar agent, ustekinumab is a monoclonal antibody directed at the p40 subunit of IL23 and IL12; thus mirikuzumab is more selective targeting of IL23. the authors examined response to the study drug at 3 doses: 50 mg, 200 mg, and 600 mg and compared to intravenous placebo. All patients received dosing at weeks 0, 4, and 8. A subset of patients continued with subcutaneous treatment starting at week 12, with 47 receiving 200 mg every 4 weeks and 46 receiving 200 mg every 12 weeks. 63% of patients in this trial had previous exposure to biologics.
- At week 12, 15.9% (50 mg), 22.6% (200 mg), and 11.5 % (600 mg) in the treatment groups achieved clinical remission compared to 4.8% of the placebo group
- Clinical responses occurred in 41.3%, 59.7%, and 49.2% in the respective treatment groups compared to 20.6% in placebo group
- At week 52, clinical remission was achieved in 46.8% of SC every 4 weeks and 37.0% every 12 weeks.
In the commentary, Danese reviews the pipeline of new drugs emerging for ulcerative colitis. Full Text Link: New Drugs in the Ulcerative Colitis Pipeline: Prometheus Unbound
A couple of key points:
- “Like Prometheus, who gave fire to humans and paid with the price of eternal torment, so the gift of new drugs in ulcerative colitis brings the consequence of patients with heterogeneous disease being cycled indiscriminately through similarly modestly effective agents.”
- “Predictive biomarkers are needed” to optimize treatment and avoid ineffective and potentially harmful treatments
My take: The emergence of new treatments is welcome given the frequent loss of response or lack of response to current therapies. Two questions: How will we decide which agent(s) is the best one to use? When will pediatric studies be available?