Lead Investigator: Shenghong Zhang, The first affiliated hospital of Sun Yat-sen University
Title of Proposal Research: Predictors and prediction model for therapeutic outcomes in patients with ulcerative colitis receiving Mirikizumab
Vivli Data Request: 10469
Funding Source: This work was supported by Guangdong Province Medical Science and Technology Research Fund (#A2024267), and the National Natural Science Foundation of China (#82270555, #82070538).
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Ulcerative colitis (UC) is a chronic, inflammatory bowel disease characterized by symptoms such as bloody diarrhea, frequent bowel movements, and abdominal discomfort. Affecting approximately 5 million people worldwide as of 2023, UC typically occurs in adolescents and adults and requires long-term treatment, significantly impacting patients’ quality of life and placing a considerable burden on families, communities, and healthcare systems.
Recent advances in UC therapy have introduced a variety of targeted medications, including biologics (type of medication made from living organisms or their products) and small molecule inhibitors (compounds that can bind to proteins and reduce their biological activity), providing new treatment options for UC patients who have not responded to traditional therapies. Mirikizumab is a type of medication designed to help people with moderate to severe UC. It works by targeting a specific part of the immune system involved in inflammation. In clinical trials, has shown efficacy and safety in the phase 3 induction (the initial high dose treatment to rapidly eliminate the symptoms of inflammation and the severity of the disease) and maintenance (treatment with a lower dose of drug to maintain the remission from the induction phase) trials in patients with moderately to severely active UC. However, some patients may still experience primary non-response to mirikizumab treatment, or lose clinical benefit over time. Among patients treated with mirikizumab, the clinical response rates at week 12 and week 52 were 24.2% and 49.9%, respectively. Therefore, it is necessary to explore potential predictors that can effectively predict the short-term and long-term outcomes of mirikizumab treatment, which will help promote personalized management of patients and improve patient prognosis.
Some predictors, such as fecal calprotectin (a protein found in feces), patient-reported outcomes (including stool frequency and rectal bleeding score of the Mayo score), and serum C-reactive protein (a protein produced by the liver in response to inflammation or infection), have been explored in studies of other biologics. However, the predictive role of these predictors for mirikizumab treatment outcomes remains unclear. This study aims to explore the predictors that can predict treatment outcomes in the early stages of mirikizumab treatment in UC and attempt to construct a prediction model to improve the predictive ability. This analysis will include data from the clinical trials of LUCENT-1 and LUCENT-2. Analyses will be conducted to assess the relationships between common predictors and outcomes of interest, and evaluate the predictive ability of the corresponding predictors. The results may help in selecting treatment approaches with clinical benefit for patients.
Requested Studies:
A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Arm, Placebo-Controlled Maintenance Study of Mirikizumab in Patients With Moderately to Severely Active Ulcerative Colitis (LUCENT 2)
Data Contributor: Lilly
Study ID: NCT03524092
Sponsor ID: 16823
A Phase 3, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Induction Study of Mirikizumab in Conventional-Failed and Biologic-Failed Patients With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)
Data Contributor: Lilly
Study ID: NCT03518086
Sponsor ID: 16591