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Center for Global Research Data

Methods for Staging disease activity In ulcerative colitis; A comparison of endoscopy and Histology (MESIAH)

Lead Investigator: Mehul Patel, King’s College Hospital NHS Foundation Trust
Title of Proposal Research: Methods for Staging disease activity In ulcerative colitis; A comparison of endoscopy and Histology (MESIAH)
Vivli Data Request: 5968
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Ulcerative colitis (UC) is a longstanding condition of the large bowel. The body’s immune system becomes overactive causing inflammation and damage to the bowel lining. Patients have symptoms of abdominal pain, diarrhoea and blood in their stool. UC mainly affects young patients aged between 15-30 years old. In the past, UC mainly affected people living in westernised nations. The number of people being diagnosed with UC is now rising in newly industrialised countries. Treatment and monitoring of UC is performed by specialists in a hospital setting. The rising number of cases is likely to place pressure on healthcare systems especially in the most resource poor settings.

The timing of decisions to start; increase; or change treatment is important. Patients with lower levels of inflammation have a reduced risk of developing bowel cancer and better quality of life. In order to make the correct treatment decisions, doctors and nurses need accurate tools to monitor inflammation.

Clinical guidelines recognise endoscopy as the best method to assess UC activity. An endoscopy involves passing a flexible camera through the back passage along the large bowel. Doctors can look directly at the bowel lining and obtain biopsies. However, endoscopy is expensive; inconvenient (bowel preparation – strong laxatives, time off work); has complications (bleeding, tears in the lining of the bowel); and limited access which can delay treatment decisions.

Symptom questionnaires are inexpensive and convenient but are inaccurate. Patients can have an absence of symptoms and still have severe inflammation during endoscopy. Similarly, severe symptoms can occur as a result of other conditions of the bowel not just UC, a questionnaire cannot distinguish this.

A stool test (faecal calprotectin) can be used as an indirect measure of bowel inflammation. Calprotectin is a protein contained within white blood cells. When the bowel is inflamed, white blood cells move to the bowel wall and release calprotectin into stool. Studies have compared calprotectin levels in stool to endoscopy. Faecal calprotectin can reliably distinguish active and inactive inflammation (remission). Some studies have suggested calprotectin results are proportional to the level of inflammation on endoscopy. This has not been reliably replicated in studies.

In summary, accurately gauging bowel inflammation is crucial to treating patients. Endoscopy is the best method available but has its limitations. There are alternative methods to endoscopy (symptoms, stools tests) but cannot, currently, be used to replace endoscopy. This is partly due to the design of studies and requirement of large-volume, reliable data to explore this. We want to use the large datasets available on the Vivli platform to help us use calprotectin in a more effective way and create a model that combines different methods of assessing inflammation as an alternative to endoscopy. We hope by creating a model that combines non-endoscopic markers of inflammation we may be able to predict the level of inflammation on endoscopy.

Requested Studies:

A Randomized, Double-Blind, Double-Dummy, Multicenter, Active-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab IV Compared to Adalimumab SC in Subjects With Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT02497469
Sponsor ID: MLN0002-3026

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT00783718
Sponsor ID: C13006

A Phase 3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Maintenance Therapy, Administered Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00488631
Sponsor ID: CR014179

A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00487539
Sponsor ID: CR014176