Applications

The Problem

Over the near to medium term, ageing populations, the rising costs of healthcare, coupled with increased scrutiny of drug pricing means that the pharmaceutical industry is facing a challenge:

How can patients receive more targeted therapeutics faster, with improved patient outcomes at a price which is acceptable to payors?

Our Solution

The pharmaceutical and biotechnology industry has been incorporating biomarker programmes into their R&D and drug development strategy.

Using biomarkers the likelihood of success of a drug from Phase 1 to Approval increases from 8.4% to 25.9%

Time to bring a drug to market

9-12 years

Average cost of development

$2.6 billion

Amount of cost incurred during phase 3 trials

60%

Drug discovery failure rate

90%+

Value of the global biomarkers market

$24 billion

5-year CAGR

14%


Value of the combined outsourced market for biomarkers and companion diagnostics

$6 billion

5-year CAGR

19%

Biomarkers can provide critical insights into clinical and therapeutic outcomes within patient cohorts:

Who is likely to respond to treatment?

For those that have had a disease, will the disease return?

What is the risk of that patient deteriorating (and at what rate)?  

Who is responding to treatment?

Who has the disease?

Indications

EpiSwitch™ technology has validated biomarkers in a wide range of diseases.

ALZHEIMER’S DISEASE

Alzheimer’s disease (AD) is the most common form of dementia, and it accounts for an estimated 60% – 80% of cases. The hallmark pathologies of AD are the progressive accumulation of the protein fragment beta-amyloid (plaques) outside neurons in the brain, and twisted strands of the protein tau (tangles) inside neurons.

The most common early symptom is short term memory loss, but with time, more parts of the brain are damaged. As this happens, new symptoms develop and become more severe. Such symptoms can include problems with language, disorientation, mood swings, loss of motivation, not managing self care, behavioural issues, and eventually leads to death. It has been estimated that there are more than 520,000 people in the UK and 35.6 million people worldwide with AD. The majority of disease cases are sporadic, or randomly occurring in the population.

At present, AD is incurable and current therapies are only palliative. Some individuals with mild cognitive impairment (MCI), a transitional state between the cognitive changes of normal ageing and very early dementia, are at increased risk of developing AD within a few years. As the average life expectancy continues to increase and the world is faced with an ageing population, there is a great need to improve early AD diagnosis; distinguish between AD and MCI; stratify which MCI cases will progress to AD; and to develop novel disease-modifying treatments for this modern epidemic. OBD programme is focused on a development of Alzheimer’s specific biomarkers for several applications.

AMYOTROPHIC LATERAL SCLEROSIS

The motor neurone disease Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s Disease) is a fatal neurodegenerative disease characterised by progressive death of the primary motor neurones in the central nervous system.

Symptoms include muscle weakness and muscle wasting, difficulty in swallowing and undertaking everyday tasks. As the disease progresses, the muscles responsible for breathing gradually fail, causing difficulty in breathing, and finally death. ALS has an average prevalence of 2 per 100,000, but is higher in the UK and USA with up to 5 per 100,000. There are estimated to be over 50,000 patients in the USA and 5,000 patients in the UK with the condition.

The mortality rate for ALS sufferers is high: the median survival from diagnosis with ALS (i.e. the time when 50% of patients have died) varies in different studies, but in the most reliable (unbiased) population studies it is about 22 months with a range of 18-30 months.

With no known cure, treatment of ALS focuses on supportive care. There is only one drug currently approved for treatment, riluzole which provides a modest increase in lifespan for ALS patients but minimal improvement in symptoms. Despite intensive research into the biological basis of ALS, diagnosis and methods of treatment, as well as monitoring of disease progression remains a challenge. Such prognostic tests would greatly benefit ALS sufferers by allowing sub-stratification of patients according to the biological mediators of clinical heterogeneity, potentially allowing a more precise prognosis and care planning by identifying fast and slow progressors.

OBD has been granted a substantial funding award from Innovate UK to develop and validate diagnostic, prognostic and predictive EpiSwitch™ biomarkers for ALS.

BREAST CANCER

Breast cancer (BCa) is the second most common cancer in the world and the most frequent cancer among women with an estimated 1.67 million new cancer cases diagnosed in 2012 (25% of all cancers).

Incidence rates vary nearly four-fold across the world regions, with rates ranging from 27 per 100,000 in Middle Africa and Eastern Asia to 96 per 100,000 in Western Europe. BCa ranks as the fifth most common cause of death from cancer overall (522,000 deaths) and while it is the most frequent cause of cancer death in women in less developed regions (324,000 deaths, 14.3% of total), it is now the second most frequent cause of cancer death in more developed regions (198,000 deaths, 15.4%), after lung cancer. Differences in BCa stage, treatments, and mortality rates are present by race and ethnicity.

BCa survival rates have been improving for forty years due to early diagnosis and available treatments. In the UK, more than 8 in 10 women survive the disease beyond five years and are twice as likely to survive for at least ten years (78%). Early diagnosis is particularly relevant when there is no effective screening methods or – as in many low-resource settings – no screening and treatment interventions implemented. In such settings, in absence of any early detection or screening and treatment intervention, patients are diagnosed at very late stages when curative treatment is no longer an option.

OBD has been developing diagnostic and prognostic epigenetic signatures for BCa, including ethnic-based differences.

DIABETES TYPE I

Diabetes mellitus type 1 (also known as T1DM; formerly insulin-dependent diabetes or juvenile diabetes) is a form of diabetes that results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger) and weight loss.

Although, T1DM accounts for 5% of all diabetes cases, it is one of the most common endocrine and metabolic conditions among children. Its cause is unknown, but it is believed that both genetic factors and environmental triggers are involved. Globally, the number of people with T1DM is unknown, although it is estimated that about 80,000 children develop the disease each year. The development of new cases varies by country and region. The United States and northern Europe fall between 8-17 new cases per 100,000 per year.

Treatment of diabetes involves lowering blood glucose and the levels of other known risk factors that damage blood vessels. Administration of insulin is essential for survival. Insulin therapy must be continued indefinitely and does not usually impair normal daily activities. Untreated, diabetes can cause many serious long-term complications such as heart disease, stroke, kidney failure, foot ulcers and damage to the eyes. Acute complications include diabetic ketoacidosis and coma.

OBD’s diabetes programme is focused on a development of EpiSwitch biomarkers for diagnostic and prognostic stratifications of T1DM.

DIABETES TYPE II

Type 2 diabetes (also known as T2DM) is the most common form of diabetes. Diabetes may occur through either, the pancreas not producing enough hormone insulin which regulates blood sugar levels, or the body not being able to effectively use the hormone it produces due to reduced insulin sensitivity.

Until recently, T2DM has only been diagnosed in adults, but it is now occurring in children and young adults. According to World Health Organisation (WHO), diabetes reached pandemic levels with 346 million sufferers worldwide and its incidence is predicted to double by 2030. In 2004 alone, approximately 3.4 million people died as a consequence of diabetes and its complications with the majority of deaths occurring in low- and middle-income countries. The incidence of T2DM is increasing due to an ageing population, changes in lifestyle such as lack of exercise and smoking, as well as diet and obesity.

T2DM is not insulin dependent and can be controlled by changes in lifestyle such as diet, exercise and further aided with medication. Individuals treated with insulin are at a higher risk of developing severe hypoglycaemia (low blood glucose levels) and thus their medication and blood glucose levels require routine monitoring. Generally, older individuals with established T2DM are at a higher risk of cardiovascular disease (CVD) and other complications and thus usually require more treatment than younger adults with a recently-recognised disease.

It has been estimated that seven million people in the UK are affected by pre-diabetic conditions, which increase the risk of progressing to T2DM. Such individuals are characterised by raised blood glucose levels, but are usually asymptomatic and thus may be overlooked for many years having a gradual impact on their health.

OBD is developing prognostic stratifications for pre-diabetic state and T2DM.

DIFFUSE LARGE B-CELL LYMPHOMA

Diffuse Large B-Cell Lymphoma (DLBCL) is a common type of non-Hodgkin lymphoma, a form of cancer which arises in the lymphatic system. Specifically, as its name suggests, DLBCL is a cancer of the B-cells of the immune system.

There are three main types of DLBCL, the first, germinal centre B-cell like (GCB) appears to arise from germinal centres (GCs) – sites within lymph nodes where mature B cells rapidly proliferate and differentiate in response to the presence of infection. Activated B-cell (ABC) DLBCL appears to arise from post GC B-cells which become blocked from differentiating into plasma cells or thymic B-cells.

The incidence of DLBCL in the US is approximately 7.14 cases per 100,000 people. The average age of diagnosis is 64 years. In people aged over 75, the incidence of DLBCL increases by 1.4% per year. In the US, DLBCL is more common in white people than in Asian or Afro-American populations and is also slightly more common in men than women.

Often the first symptom of DLBCL is a painless but rapid swelling in one of the lymph nodes. The lymph nodes most commonly involved include those in the neck, armpit and groin. In about 40% of cases the cancer does not begin in the lymph nodes (extranodal disease), and instead originates in sites such as the lungs, GI tract, skin or bone marrow. Systemic symptoms or ‘B-class symptoms’ may include night sweats, unintentional weight loss of greater than 10% and fever.

If DLCBL is suspected then a biopsy of the affected area will be performed. A pathologist will then look at the tissue under a microscope and make a decision based on the appearance of the cells. Once a diagnosis of DLCBL has been made then the patient will undergo a combination of the following tests and scans; bone marrow tests, blood tests, PET scans, X-rays and CT scans in order to determine how far the disease has spread, which organs are involved and how much it is affecting them.

Generally the prognosis for someone with DLBCL is fairly good when compared with other types of cancer common to the same age group. Patients with GCB DLBCL are more likely to survive at least 5 years post treatment (60%) compared to 35% and 38% for ABC DLBCL and type III DLBCL respectively. The differences in gene expression between both types, ABC and GCB DLBCL, are very diverse which makes their accurate stratification a challenge.

LIVER CANCER

Liver cancer occurs more often in less developed regions where 83% (50% in China alone) of the estimated 782,000 new cancer cases worldwide occurred in 2012. It is the fifth most common cancer in men (554,000 cases, 7.5% of the total) and the ninth in women (228,000 cases, 3.4%).

Large increases in incidence, especially in younger age groups, have been observed in the USA primarily due to heavy alcohol intake, rising obesity, diabetes and hepatitis B and C infections. Liver cancer is the second most common cause of death from cancer worldwide, estimated to be responsible for nearly 746,000 deaths in 2012 (9.1% of the total).

The prognosis for liver cancer is very poor , and as such the geographical patterns in incidence and mortality are similar. Liver malignancy is often diagnosed at a late stage when it shows resistance to conventional chemotherapy and treatment options are limited. Only 10% of people are diagnosed at an early stage when the tumour can be surgically removed.

There are no widely recommended screening tests to detect liver cancer at an early stage. Blood tests and ultrasound have been recommended worldwide for people at a higher risk, but the use and accuracy of alpha fetoprotein (AFP) blood test for screening are being questioned. Some liver tumours, especially early liver cancer, do not produce high enough levels of AFP to signify the presence of the tumour, while other non-cancerous diseases can also raise AFP levels.

OBD’s established EpiSwitchTM platform has been used to develop diagnostic and prognostic liver cancer tests.

MELANOMA

Malignant melanoma is the least common, but most aggressive form of skin cancer. It occurs in melanocytes, cells responsible for synthesis of the dark pigment melanin. The majority of malignant melanomas are caused by heavy UV exposure from the sun. Most of the new melanoma cases are believed to be linked to behavioural changes towards UV exposure from sunlight and sunbeds.

Globally, in 2012, melanoma occurred in 232,000 people and resulted in 55,000 deaths. Incidence rates are highest in Australia and New Zealand. The worldwide incidence has been increasing more rapidly amongst men than any other cancer type and has the second fastest incidence increase amongst women over the last decade.

The survival rates are very good for individuals with stage 1 and 2 melanomas. However, only 7 – 19% of melanoma patients whose cancer has spread to distant lymph nodes or other parts of the body will live for more than 5 years.

Currently, the only way to accurately diagnose melanoma is to perform an excision biopsy on the suspicious mole. The treatment includes surgical removal of the tumour. There is no melanoma screening programme in the UK, but educational programmes have been created to raise awareness of risks and symptoms of melanoma. There is a high demand for screening programmes in countries where melanoma incidence is very high e.g. in Australia.

OBD has been working extensively to address different utility questions in melanoma including development of EpiSwitch™ biomarkers for diagnosis, prognosis, residual disease monitoring and companion diagnostics for melanoma immunotherapies.

MULTIPLE SCLEROSIS PRIMARY PROGRESSIVE

Multiple sclerosis (MS) is an acquired chronic immune‑mediated inflammatory condition of the central nervous system (CNS), affecting both the brain and spinal cord.

The cause of MS is unknown. It is believed that an abnormal immune response to environmental triggers in people who are genetically predisposed results in immune‑mediated acute, and then chronic, inflammation. The initial phase of inflammation is followed by a phase of progressive degeneration of the affected cells in the nervous system.

MS is more common among people in Europe, the United States, Canada, New Zealand, and sections of Australia and less common in Asia and the tropics. It affects approximately 100,000 people in the UK. In the US, the number of people with MS is estimated to be about 400,000, with approximately 10,000 new cases diagnosed every year. People with MS typically develop symptoms between the ages 20 and 40, experiencing visual and sensory disturbances, limb weakness, gait problems, and bladder and bowel symptoms. They may initially have partial recovery, but over time develop progressive disability.

Although, there is no cure, there are many options for treating and managing MS. They include drug treatments, exercise and physiotherapy, diet and alternative therapies. MS is a potentially highly disabling disorder with considerable personal, social and economic consequences. People with MS live for many years after diagnosis with significant impact on their ability to work, as well as an adverse and often highly debilitating effect on their quality of life and that of their families. OBD’s MS programme involves looking at prognostic stratifications between primary progressive and relapsing-remitting MS.

Primary progressive multiple sclerosis (MSPP) occurs in 10% to 15% of people with MS. MSPP sufferers do not experience well-defined attacks but their symptoms continually worsen from the time of diagnosis with little or no recovery. Several aspects of PPMS distinguish it from other types of MS. People with MSPP are usually older at the time of diagnosis – an average age of 40. Approximately equal numbers of men and women develop primary progressive MS. In other types of MS, women outnumber men three to one. Response to treatment is very poor in those individuals. Primary progressive MS usually leads to disability earlier than relapsing-remitting MS.

MULTIPLE SCLEROSIS RELAPSING REMITTING

Multiple sclerosis (MS) is an acquired chronic immune‑mediated inflammatory condition of the central nervous system (CNS), affecting both the brain and spinal cord.

The cause of MS is unknown. It is believed that an abnormal immune response to environmental triggers in people who are genetically predisposed results in immune‑mediated acute, and then chronic, inflammation. The initial phase of inflammation is followed by a phase of progressive degeneration of the affected cells in the nervous system.

MS is more common among people in Europe, the United States, Canada, New Zealand, and sections of Australia and less common in Asia and the tropics. It affects approximately 100,000 people in the UK. In the US, the number of people with MS is estimated to be about 400,000, with approximately 10,000 new cases diagnosed every year. People with MS typically develop symptoms between the ages 20 and 40, experiencing visual and sensory disturbances, limb weakness, gait problems, and bladder and bowel symptoms. They may initially have partial recovery, but over time develop progressive disability.

Although, there is no cure, there are many options for treating and managing MS. They include drug treatments, exercise and physiotherapy, diet and alternative therapies. MS is a potentially highly disabling disorder with considerable personal, social and economic consequences. People with MS live for many years after diagnosis with significant impact on their ability to work, as well as an adverse and often highly debilitating effect on their quality of life and that of their families. OBD’s MS programme involves looking at prognostic stratifications between primary progressive and relapsing-remitting MS.

The most common (approx. 90%) pattern of disease is relapsing–remitting MS (MSRR). Most people with this type of MS first experience symptoms in their early 20s. After that, there are periodic attacks (relapses), followed by partial or complete recovery (remissions).The pattern of nerves affected, severity of attacks, degree of recovery, and time between relapses all vary widely from person to person. Eventually, around two‑thirds of people with relapsing-remitting MS enter a secondary progressive phase of MS. This occurs when there is a gradual accumulation of disability unrelated to relapses, which become less frequent or stop completely.

NASOPHARYNGEAL CANCER

Nasopharyngeal carcinoma (NPC) is a cancer originating in the nasopharynx, the uppermost region of the pharynx or “throat”, where the nasal passages and auditory tubes join the remainder of the upper respiratory tract.

Worldwide, there are 80,000 incident cases and 50,000 deaths of NPC annually. NPC is uncommon in the United States and most other nations, but is vastly more common in certain regions of East Asia and Africa. While NPC is seen primarily in middle-aged persons in Asia, a high proportion of African cases appear in children. The cause of increased risk for NPC in these endemic regions is not entirely clear but there are viral (exposure to Epstein-Barr virus (EBV)), dietary (nitrosamines in South East Asian diet), and genetic factors implicated in its causation.

At present the diagnosis of NPC remains a challenge as the general signs and symptoms resemble other conditions. These can include enlarged cervical lymph nodes, nosebleeds, nasal obstruction, diminished hearing, tinnitus, otitis media, cranial nerve dysfunction, sore throat and headache. However, in areas of the world where NPC is much more common, for instance in some areas of China, screenings may be offered to people thought to be at high risk of the disease. NPC produces few symptoms early in its course which results in most cases being detected at advanced stages. As with any cancer, the prognosis depends on the stage, type, and size of the tumour as well as the patient’s age and general health.

OBD has developed epigenetic signatures for early disease diagnosis.

PROSTATE CANCER

Prostate cancer (PCa) is the second most common cancer in men with an estimated 1.1 million men being diagnosed worldwide in 2012. PCa incidence varies more than 25-fold worldwide with the rates being the highest in Australia/New Zealand and Northern America, and in Western and Northern Europe, because the practice of prostate specific antigen (PSA) testing and subsequent biopsy has become widespread in those regions.

With an estimated 307,000 deaths in 2012, PCa is the fifth leading cause of death from cancer in men. Mortality rates are generally high in predominantly black populations (Caribbean and sub-Saharan Africa). Age is the main risk factor for prostate cancer, predominantly affecting men over the age of 50, with the average age of diagnosis being between 70 and 74 years. Men with a family history of prostate cancer and men of black African and black Caribbean descent are more at risk suggesting that important genetic determinants of risk also exist.

The prognosis of prostate cancer has improved over the years, with almost 9 out of 10 prostate cancers being found at an early stage, but the survival trends are difficult to interpret. The rising survival rates are somewhat due to an earlier detection of tumours. However, it has been estimated that lead-time bias, which is defined as the difference in time between screen detection and clinical detection in the absence of screening, is also contributing to the rising survival rates.

Five-year relative survival worldwide is 90% or more for disease which is confined to the prostate, but this falls to 30% for patients with metastatic disease at presentation. The use of the PSA testing is controversial as it often results in false positives and no definite diagnosis. Combining it with subsequent biopsy is far from optimal as there are possible side effects such as impotence and incontinence. Also, some aggressive tumour types are not associated with an increase in PSA levels making them difficult to detect.

For these reasons, there is no approved screening programme for prostate cancer, but PSA testing may be offered to men over the age of 50 who are at increased risk of prostate cancer. Thus, there is a great need to find better ways to detect PCa early and differentiate which cancers will spread quickly compared to slower-growing tumours.

OBD’s EpiSwitch™ platform has been employed to develop diagnostic and prognostic PCa signatures.

RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA), is an autoimmune systemic disease that affects the joints, connective tissues, muscle, tendons, and fibrous tissue.

It tends to strike during the most productive years of adulthood, between the ages of 20 and 40, often causing pain and deformity. In addition to causing joint problems, RA can also affect other organs of the body such as the skin, eyes, lungs and blood vessels. The disease follows alternate periods of increased disease activity (flares) and relative recovery (remission).

The prevalence varies between 0.3% and 1% and is more common in women and in developed countries. RA is the second most common form of arthritis in the UK and the most common inflammatory joint disorder. Disease diagnosis is currently via general clinical presentation with subsequent treatment based on clinical guidelines. Although this is the standard of care, it is flawed in many respects due to diverse disease phenotypes and genotypes.

Treatment focuses on controlling symptoms and preventing joint damage. Disease-modifying anti-rheumatic drugs (DMARDs) may slow or halt the progress of the disease. Biological DMARDS are effective but not all patients respond to a particular DMARD, while others experience hypersensitivity to these agents. The clinical management of RA is fraught with many challenges, not least among these is the crucial need for clinicians to diagnose patients early and put them on the appropriate medication for the prevention of disease progression.

OBD’s RA programme is focused on a development of several disease-specific stratifications.

SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE), also known as discoid lupus or disseminated lupus erythematosus, is an autoimmune disease which affects the skin, joints, kidneys, brain, and other organs. Although “lupus” includes a number of different diseases, SLE is the most common type of lupus.

SLE is a disease with a wide array of clinical manifestations including rash, photosensitivity, oral ulcers, arthritis, inflammation of the lining surrounding the lungs and heart, kidney problems, seizures and psychosis, and blood cell abnormalities. Symptoms can vary and can change over time and are not disease specific which makes diagnosis difficult.

It occurs from infancy to old age, with peak occurrence between ages 15 and 40. The reported prevalence of SLE in the population is 20 to 150 cases per 100,000. In women, prevalence rates vary from 164 (white) to 406 (African American) per 100,000. Due to improved detection of mild disease, the incidence nearly tripled in the last 40 years of the 20th century. Estimated incidence rates are 1 to 25 per 100,000 in North America, South America, Europe and Asia.

The exact cause of SLE is not known, but several factors have been associated with the disease. People with lupus often have family members with other autoimmune conditions. There may be environmental triggers like ultraviolet rays, certain medications, a virus, physical or emotional stress, and trauma.

There is no cure for SLE and the treatment is to ease the symptoms. These will vary depending on expressed symptoms and may include anti-inflammatory medications, steroids, corticosteroids and anti-malarial drugs. Survival has been improving, suggesting that more or milder cases are being recognised. OBD has been developing prognostic signatures for SLE.

THYROID CANCER

Thyroid cancer is one of the rarer types of cancer (accounting for 2.1% of all cancers) with 298,000 new cases and approximately 40,000 deaths in 2012 worldwide. It is more common in women where it tends to occur between the ages of 35 and 39, whilst in men it is more likely to occur above the age of 70.

Thyroid cancer is thought to be related to a number of environmental and genetic predisposing factors, but uncertainty remains regarding its causes. Environmental exposure to ionising radiation from both natural background sources and artificial sources are suspected to play a significant role. Thyroiditis and other thyroid diseases may also predispose to thyroid cancer.

The symptoms of thyroid cancer can include a lump at the base or elsewhere in the neck, persistent hoarse voice, sore throat or difficulty swallowing. Thyroid lumps are very common, but only approximately 5% of those are cancerous. The prognosis of thyroid cancer is related to the type and stage of cancer at the time of diagnosis. For the most common form of thyroid cancer – papillary – the overall prognosis is very good and the five-year survival rate is approximately 98%. The incidence of thyroid cancer has been increasing in the past few decades, which is likely to be related to an increase in early diagnosis.

Although most patients with thyroid cancer have a good outcome when treated with standard therapies, the prognosis for those with resistant or recurrent disease is poor. Management options for thyroid cancer include observation, surgery, radioiodine therapy and pharmacotherapy. Some controversies exist with regards to the optimal management approaches in patients with differing types of thyroid cancer. The origin and characteristics of thyroid cancers are important factors influencing disease progression and response to therapy. Therefore, novel findings on the aetiology and pathophysiology of these neoplasms and the identification of new disease biomarkers are likely to substantially improve disease management, thereby contributing to more tailored therapeutic decisions.

OBD’s thyroid programme is focused on a development of EpiSwitch™ biomarkers for early diagnosis of thyroid cancer.

ULCERATIVE COLITIS

Ulcerative colitis (UC), a chronic inflammatory disease of the gastrointestinal tract, is the most common type of inflammatory disease of the bowel, with an incidence of 10 per 100,000 people annually, and a prevalence of 243 per 100,000. Although, UC can occur in people of any age, it is more likely to develop in people between the ages of 15 and 30 and older than 60.

The exact cause of ulcerative colitis is unknown. However, it is believed that an overactive intestinal immune system, family history and environmental factors (e.g. emotional stress) may play a role in causing UC. It is more prevalent in people of Caucasian and Ashkenazi Jewish origin than in other racial and ethnic subgroups. The most common signs and symptoms of this condition are diarrhoea with blood or pus and abdominal discomfort. It can also cause inflammation in joints, spine, skin, eyes, and the liver and its bile ducts. UC diagnosis is carried out through taking family history, physical exam, lab tests and endoscopy of large intestine.

This lifelong disease is associated with a significant morbidity, and the potential for social and psychological sequelae particularly if poorly controlled. An estimated 30–60% of people with ulcerative colitis will have at least one relapse per year. About 80% of these are mild to moderate and about 20% are severe. Approximately 25% of people with UC will have one or more episodes of acute severe colitis in their lifetime. Of these, 20% will need a surgical removal of all or part of the colon (colectomy) on their first admission and 40% on their next admission.

Although mortality rates have improved steadily over the past 30 years, acute severe colitis still has a mortality rate of up to 2%. Mortality is directly influenced by the timing of interventions, including medical therapy and colectomy. Ulcerative colitis has a well documented association with the development of colorectal cancer, with greatest risk in longstanding and extensive disease. Treatment of relapse may depend on the clinical severity, extent of disease and patient’s preference and may include the use of aminosalicylates, corticosteroids or immunomodulators. The resulting wide choice of agents and dosing regimens has produced widespread heterogeneity in management across the UK, and emphasises the importance of comprehensive guidelines to help healthcare professionals provide consistent high quality care. OBD programme is focused on a development of disease-specific signatures for UC.