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Background information
Inflammatory bowel disease
Inflammatory bowel disease (IBD) encompasses a group of long-term disorders, including ulcerative colitis (UC)
and Crohn’s disease, which produce inflammation and ulceration of the gastrointestinal tract (gut). Crohn’s disease
can also penetrate through the gut wall, leading to significant complications. In both disorders, tissue destruction
results from a damaging inflammatory response involving the recruitment and activation of leukocytes (white blood
cells). UC only affects the colon (large intestine), while Crohn’s disease can affect the entire digestive system, from
the mouth to the anus. It is sometimes difficult to tell the difference between the two main types of IBD: such cases
are known as indeterminate colitis.1
Causes
The exact causes of UC and Crohn’s disease are unclear. It is thought that several factors have a part to play, such as:
•Genetics: there is evidence that people are more likely to develop IBD if they have a close relative with the
condition1
•Several environmental risk factors have also been proposed to contribute to IBD pathogenesis, including
smoking and diet. However, the results from the supporting studies are inconsistent, and the limitations of these
studies preclude drawing firm conclusions 2–4
•Disruption to the immune system (the body’s defence against infection): UC and Crohn’s disease are
autoimmune conditions. Inflammation may be caused by an altered, dysregulated immune response
characterised by the immune system attacking healthy tissue inside the digestive system and by an excessive
response whilst fighting off infection from a virus or bacteria. Exactly what causes the immune system to behave
in this way is unclear. Most experts think it is a combination of genetic and environmental factors1
Epidemiology
•IBD occurs most frequently in people in their late teens and twenties. Men and women have an equal chance of
getting the disease5
•Within Europe and North America, there is a north-to-south gradient in the frequency of IBD in populations.
This difference in incidence correlates with the highest frequency of IBD in temperate climates and the more
industrialised parts of the world, such as Western Europe and North America, and the lowest frequency in
developing regions with warmer climates and in rural areas
•About 1.4 million people in the US and 2.2 million in Western Europe suffer from UC and Crohn’s disease6
•Overall, the prevalence of IBD is 396 cases per 100,000 persons annually2
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•A review of IBD reported that the prevalence of Crohn’s disease in North America is 319 per 100,000 persons,
whereas in Europe it is 322 per 100,000 persons.2 Prevalence rates of ulcerative colitis were reported as 249 per
100,000 persons in North America and 505 per 100,000 persons in Europe2
•In most Western European countries, the incidence of IBD has stabilised or slightly increased. Increases have
been reported from some high-incidence areas (e.g. Denmark and Sweden)7
Symptoms
The main symptoms of UC and Crohn’s disease are similar (Figure 1). They include:1
• Abdominal pain: this is more common in Crohn’s disease than in UC
• Recurring or bloody diarrhoea
• Weight loss
• Extreme tiredness
Not everyone has all these symptoms, and some people may experience additional ones, such as nausea and fever.
Some may also experience periods of severe symptoms (‘flare-ups’), and go through long periods when they have
few or no symptoms at all (remission).1
Crohn’s disease
Ulcerative colitis
• Age of onset 20–30 years
• Confined to sigmoid/colon
• Bloody, frequent bowel
movements
• Age of onset 15–30 years
• Most common in ileum
and ascending colon
• Abdominal pain, diarrhea,
vomiting, weight loss
• Fistulae and strictures
Figure 1: Comparison of UC and Crohn’s disease
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Possible complications
Complications of IBD can include:1,5
•Malnutrition
• Colon cancer (mostly in UC)
•Fistula in patients with Crohn’s disease (an ulcer that extends through the bowel wall, creating a hole between
different parts of the digestive tract). Fistulas occur frequently around the anus and rectum. They can become
infected and may result in abscess formation. Treatment programmes are used to manage infected fistulas, but
surgery is often needed
• Intestinal rupture
• Bowel obstruction
In rare cases, a severe flare-up of IBD can put the patient into shock, and this can be life threatening. In the case of a
flare-up, shock is usually caused by blood loss during a sudden and prolonged episode of bloody diarrhoea.
Diagnosis
The gastroenterologist must take the patient’s medical history and perform a physical examination. The exam may
include blood tests and samples of a bowel movement. The patient may also need to undergo a colonoscopy (a small
flexible tube is inserted into the anus and slowly passed along the colon, allowing the doctor to see the lining of the
colon). If necessary, the doctor can take a tissue sample (called a biopsy) to make a diagnosis. For Crohn’s disease,
a small bowel X-ray, computerised tomography (CT) scans, magnetic resonance imaging (MRI) scans, or capsule
endoscopy may also be required.5
Treatment1,5
Currently, there is no cure for UC or Crohn’s disease. Treatment aims to relieve symptoms and prevent them
from returning. Mild UC may not require treatment because symptoms can clear up after a few days. Otherwise,
medications may include:
•Anti-inflammation drugs: aminosalicylates or, in more severe cases, corticosteroids
• Immunosuppressants – to block the harmful activities of the immune system
•Biological treatments: some patients may require medications that target specific proteins in the body’s immune
system to help control the development of inflammation. Tumor necrosis factor (TNF) can cause the immune
system to attack healthy tissues in the body and cause inflammation and damage. Anti-TNF medications bind to
TNF or its receptor to block its action. Another target is a membrane-bound extracellular protein called ‘beta 7
integrin’. Humanised monoclonal antibodies being investigated for treatment of UC and Crohn’s disease bind to
two integrin receptors, alpha4-beta7 and alphaE-beta7, preventing inflammatory cells from entering and being
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retained in the gut mucosa. One of the receptors (alphaE-beta7) may also have biomarker potential to predict
which subgroup of patients will respond best to treatment
An estimated 20% of people with UC have severe symptoms that often do not respond to medication. In these cases,
it may be necessary to surgically remove an inflamed section of the digestive system. Around 60–75% of people
with Crohn’s disease will require surgery to repair damage to their digestive system and to treat complications of the
condition.
In order to address the current significant unmet need for IBD treatment, Roche is investigating a monoclonal
antibody for the treatment of UC and Crohn’s disease.
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References
1.NHS. Inflammatory bowel disease. Available from: http://www.nhs.uk/conditions/Inflammatory-bowel-disease/Pages/
Introduction.aspx. Accessed 23 January 2015
2.Rowe W et al. Medscape. Inflammatory bowel disease, epidemiology. Available from: http://emedicine.medscape.com/
article/179037-overview#a0156. Accessed 23 January 2015
3. Geremia A et al. Innate and adaptative immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13: 3–10
4. Marsal J and Agace W. Targeting T-cell migration and inflammatory bowel disease. J Intern Med 2012; 272: 411–29
5.American Gastroenterological Association. Available from: http://www.gastro.org/patient-center/digestive-conditions/
inflammatory-bowel-disease. Accessed 23 January 2015
6.Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences.
Gastroenterology 2004; 126: 1504–17
7.Medscape. Crohn’s Disease, epidemiology. Available from: http://emedicine.medscape.com/article/172940-overview#a0156.
Accessed 23 January 2015
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