Lead Investigator: Shenghong Zhang, The first affiliated hospital of Sun Yat-sen University
Title of Proposal Research: Dynamics of Disease Activity in Monitoring Therapeutic Outcomes and Predicting Prognosis for Crohn’s disease
Vivli Data Request: 10037
Funding Source: This research is funded by the National Natural Science Foundation of China (#82270555, #82070538, #82000520).
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Crohn’s disease (CD) is a chronic, recurrent inflammatory bowel disease, with symptoms such as diarrhea, stomach aches and cramps, blood in the stool, tiredness and weight loss. For developed countries in Europe and America, the incidence of CD ranges from 0.4 to 20.0 per 100,000 person-years, with a prevalence ranging from 1.5 to 322 per 100,000 persons. However, in developing countries, the prevalence of CD is showing a rapidly increasing trend.
In recent years there has been a surge in the development of targeted therapies for CD, which specifically target the immune system of the gut, rather than the more traditional non-targeted treatments which affected the whole body, which has expanded the therapeutic options for CD. However, not all CD patients benefit from treatment with targeted therapies. Therefore, timely monitoring of disease activity and prediction of therapeutic response are vital processes during therapies, especially in the initial year of treatment.
Describing the trajectory of a disease course (the path it follows) is a promising topic in current clinical research. Fecal calprotein is a protein found in the stool. High levels of calprotectin usually mean that the intestines are inflamed, and the higher the level, the more inflammation there is. This is an indicator of Crohn’s disease, and its severity. For CD, four different trends in fecal calprotein levels have been observed in patients studied in the five years from diagnosis, with better outcomes correlating with receiving drug therapy early after diagnosis. Recently, trajectories of clinical symptoms, psychological evaluations, health-related quality of life and biomarkers (molecules found in blood, other body fluids, or tissues that are a sign of a condition or disease)(were explored in newly diagnosed ulcerative colitis. Ulcerative colitis is also an inflammatory bowel disease, but with more localized inflammation in the lower intestine. One of our previous studies has observed that the trajectory of fecal lactoferrin (a protein found in the stool that is indicative of ulcerative colitis) when a UC patient started biologic therapy was associated with symptom remission after one year. In this way, trajectories could be a promising method for disease course monitoring and prognosis predicting in various disease including Crohn’s disease, although relatively few studies towards this have been reported in CD patients.
Therefore, in order to investigate the role of disease activity trajectories in therapeutic efficacy monitoring and prognosis predicting, this study will analyze the patient-level data during targeted therapy from seven randomized clinical trials, including VERSIFY[NCT02425111], UNITI-1 [NCT01369329], UNITI-2 [NCT01369342], IM-UNITI [NCT01369355], and EXTEND[NCT00348283].
Requested Studies:
An Open-Label Phase 3b Study to Assess Mucosal Healing in Subjects With Moderately to Severely Active Crohn’s Disease Treated With Vedolizumab IV
Data Contributor: Takeda
Study ID: NCT02425111
Sponsor ID: MLN0002-3028
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects With Moderately to Severely Active Crohn’s Disease Who Have Failed or Are Intolerant to TNF Antagonist Therapy (UNITI-1)
Data Contributor: Johnson & Johnson
Study ID: NCT01369329
Sponsor ID: CR018415
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Subjects With Moderately to Severely Active Crohn’s Disease
Data Contributor: Johnson & Johnson
Study ID: NCT01369355
Sponsor ID: CR018421
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab Endoscopy Trial to Evaluate the Effects on Mucosal Healing in Subjects With Crohn’s Disease Involving the Colon
Data Contributor: AbbVie
Study ID: NCT00348283
Sponsor ID: M05-769
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects With Moderately to Severely Active Crohn’s Disease (UNITI-2)
Data Contributor: Johnson & Johnson
Study ID: NCT01369342
Sponsor ID: CR018418