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June 21, 2016: Several therapies exist to help treat inflammatory bowel disease (IBD) and improve patient quality of life. However, a growing number of gastroenterologists and patients have been choosing to stop these therapies - a process known as de-escalation. There is currently no standard of care for de-escalating inflammatory bowel disease therapies, but gastroenterologists and researchers are investigating biomarkers such as fecal calprotectin in order to develop one¹.

Research estimates 1.6 million Americans suffer from either Crohn’s disease (CD) or ulcerative colitis (UC) which are two forms of IBD^2,5. America is not alone with this disease burden; Canada, Denmark, Iceland, and the United Kingdom all have high incident rates of both CD and UC as well². The average yearly cost of having Crohn's disease per patient in the U.S. ranges from $8,256 - $18,963, and between $5,066 - $15,020 for patients with ulcerative colitis^3,4.

There is no cure for IBD, but there are therapeutic options available to patients that can help them work towards control of symptoms and possibly remission. Current IBD therapies are designed to control inflammation and include immunomodulators and anti-TNFα, or a combination of both⁵. Immunomodulators and anti-TNFα drugs lower the body’s immune response which may increase the body’s ability to defend and fight against infections^6,7.

Although these therapies work for many IBD patients, there are reasons why gastroenterologists and patients consider reducing or stopping these therapies, also known as de-escalating. Some of these reasons include cost, concerns over drug toxicity, and patient age¹. Furthermore, one commonly used IBD therapy drug called thiopurine may cause tumor development8, which is especially worrisome for patients over the age of 60¹. It’s easy to understand why de-escalation of IBD treatment is a current topic of interest not only for gastroenterologists, but also patients. Currently, there is no clinical standard for de-escalating IBD therapies.  In order to consider de-escalation, some gastroenterologists look for the level of remission, length of remission, inflammation markers, bowel healing, age, and type of therapy being used¹. One review analyzed 69 IBD de-escalation studies totaling 4,672 patients. The review concluded that 50% of IBD patients who stop their therapy have relapses; however, it is still possible for de-escalation to work successfully for some patients⁵. One common challenge with de-escalating IBD therapies is figuring out a method to monitor patients and catch flare ups before they occur¹. A possible way to monitor IBD de-escalation in patients is to use biomarkers such as fecal calprotectin (FC).

Calprotectin (MRP 8/14, S100 A8/A9) is an immunomodulatory protein found in neutrophil granulocytes and macrophages. It plays a central role in neutrophil defenses and inflammatory pathologies. Under conditions of mucosal inflammation, studies have shown that calprotectin is released into the gastrointestinal lumen, therefore serving as a useful biomarker to accurately identify intestinal inflammation⁹.  Additionally, measuring calprotectin can help detect inflammation prior to the appearance of clinical symptoms¹⁰. Therefore, monitoring levels of fecal calprotectin may help predict potential relapses in IBD patients, as well as allow gastroenterologists to intervene in the de-escalation process before a flare up occurs.  

BIOCYCLE is a comprehensive study in Europe working towards assessing the effectiveness of biomarkers in monitoring and predicting inflammatory bowel disease relapse in de-escalation patients, including calprotectin¹¹. Research, such as the BIOCYCLE project, are moving gastroenterologists closer to creating a standard of care for IBD de-escalation and improving the lives of patients around the globe. Additionally, this study could help patients and gastroenterologists alike better understand the pros and cons of de-escalating inflammatory bowel disease therapies. 

1. Dunleavy. (2016). Standing down: De-escalating treatment in IBD. Gastroenterology and Endoscopy News, 67(4), 20-22.
2. Crohn’s and Colitis Foundation of America. (2014). Facts About Inflammatory Bowel Diseases. CCFA.org.
3. Kappelman et al. (2008). Direct health care costs of Crohn’s disease and ulcerative colitis in US children and adults. Gastroenterology, 135(6), 1907-1913.
4. Gibson et al. (2008). The direct and indirect cost burden of Crohn’s disease and ulcerative colitis. Occup. Environ. Med., 50, 1261-1272.
5. Torres et al. (2015). Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients with inflammatory bowel disease. Gastroenterology, 149, 1716-1730.
6. Crohn’s and Colitis Foundation of America. (2009). Immunomodulators. CCFA.org.
7. Crohn’s and Colitis Foundation of America. (2014). Biologic Therapies. CCFA.org.
8. Neurath. (2010). Thiopurines in IBD: What is their mechanism of action? Gastroenterol. Hepatol., 6(7), 435–436. PMCID: PMC2933759.
9. Manz et al. (2012). Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: An observational study. BMC Gastroenterol. PMID: 22233279.
10. Tibble et al. (2000). A simple method for assessing intestinal inflammation in Crohn’s disease. Gut, 47(4), 506-513. PMID: 10986210.
11. Dieupart et al. (2016). Biocycle. Biocycle Project.