Colorectal Cancer :: Mesalazine to prevent colorectal cancer in IBD

Speaking at a Ferring-sponsored symposium on the occasion of the 14th United European Gastroenterology Week (UEGW) congress, Christoph Gasche, Associate Professor of Medicine, Medical University of Vienna, Austria presented the findings of an in-vitro study which for the first time demonstrates a mode of action by which mesalazine may reduce the risk of colorectal cancer in Inflammatory Bowel Disease (IBD) patients.

Doctors have been treating the symptoms of IBD very effectively over many years to improve the quality of life for patients. Whilst previous studies suggest that long-term maintenance therapy with aminosalicylates, such as mesalazine, may diminish the disease activity, theories now indicating that molecules such as mesalazine may also have a long-term additional benefit of reducing the otherwise increased risk of such patients developing colorectal cancer.1,2

Professor Gasche has identified two related modes of action which explain this phenomenon. According to his research, treatment with mesalazine initially activates a cell cycle checkpoint during the S Phase of the cell cycle when replication of the potentially cancerous cells takes place.3 This slows down the cell replication, which then improves the fidelity of the replication so that less code errors are made. Mesalazine has been shown to reduce the error rate by 20%.10

For Professor Gasche, the lesson of these findings is clear. ?For people with colitis and a risk of IBD, taking mesalazine on a regular basis could prevent cancer in the long-term.”

It has been estimated that in patients with extensive ulcerative colitis the incidence of developing colorectal cancer after 30 years is as high as 18%.4 As such, colorectal cancer is a very serious complication and causes 1 in 6 of all deaths in people aged below 50 years who suffer from IBD.5

Speaking at the same symposium, Michael Kamm, Professor of Gastroenterology and Chairman of Medicine at St Mark?s Hospital, London, UK, outlined previous studies which showed that treatment with mesalazine could reduce the risk of colorectal cancer by as much as 81%.1

“Patients with ulcerative colitis are often aware of their increased risk of colorectal cancer, and are keen to reduce that risk,” comments Rod Mitchell, Chairman of the 23-member association IBD patient group, the European Federation of Crohn?s and Ulcerative Colitis Associations (EFCCA). “The results of Prof Gasche’s research provide us with new evidence which may move us further along this complex pathway so helping to reduce that risk.”

Inflammatory Bowel Disease (IBD)
IBD describes a range of chronic diseases of the gastrointestinal system, encompassing Ulcerative Colitis (UC) and Crohn?s Disease (CD). IBD is characterised by intermittent flares with debilitating symptoms (such as diarrhoea, abdominal pain and weight loss) that can result both in a significant worsening of the patient?s quality of life as well as causing emotional distress and social isolation. In addition, patients can also suffer from a number of serious complications of the disease and may require life-long treatment and often surgery.

Both CD and UC are ongoing diseases and, although symptoms may disappear with treatment, they tend to come back over time. Thus, patients are at risk of future attacks unless they continue to take their medication to keep them in remission.

During the acute, active phase of IBD doctors may prescribe stronger therapies to control the inflammation, despite their potential harmful effects, if they will help the patient get better. However, side effects from a treatment being used for maintenance therapy are far less acceptable. Since patients will most probably have to take these medications over their entire lifetime, they must be both effective and safe. Mesalazine fulfils these requirements, as well as being convenient for the patient.

Incidence of IBD
IBD is mainly a condition of the industrialised world. It affects men and women equally and all races, although it is more common in some races than others. In Northern Europe and the USA, the number of people affected by UC is approximately 120?270 per 100,000 ? that is 1 in every 370?830 people6,7,8 ? with between 3?25 new cases per 100,000 people diagnosed each year.

For CD, the number of people affected is approximately the same, with 145 per 100,000 affected, and between 6?8 new cases per 100,000 people diagnosed each year.6,7,8 However, unlike UC, the number of new cases of CD each year is increasing, particularly in young people, although the reasons for this are unclear.9

References
1. Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J. Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther 2000;14:145?153.
2. Van Staa TP et al. Gut. 2005; 54: 1573?1578.
3. Luciani MG et al, Gastroenterology 2006, in press
4. Eaden et al. Gut 2001; 48: 526?535.
5. Gyde S et al. Gastroenterology 1982; 82: 36?43.
6. Rubin GP et al. Aliment Pharmacol Ther 2000; 14(12): 1553?1559
7. Farrokhayr F et al. Scand J Gastroenterol. 2001; 36(1): 2?15
8. Satsangi J and Sutherland L (2003) In: Inflammatory Bowel Disease, Churchill Livingstone
9. Loftus EV et al. Gastroenterology 1998; 114: 1161?1168
10. Gasche C et al, Cancer Res 2005; 65:3993-7

About Ferring
Ferring is a Swiss-based research driven, speciality biopharmaceutical group active in global markets. The company identifies, develops and markets innovative products in the areas of endocrinology, gastroenterology, gynaecology, fertility and urology. In recent years Ferring has expanded beyond its traditional European base and now has offices in over 40 countries.


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