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Advancements in the Diagnosis and Therapeutics of Ulcerative Colitis (UC)

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BMS recently published the result of the critical phase III True North study (NCT02435992) that assessed Zeposia (ozanimod) as an induction and maintenance therapy for adult patients with moderate to severe ulcerative colitis (UC). It is worth mentioning that Zeposia is the first in history an oral sphingosine-1-phosphate (S1P) receptor modulator to show clinical benefits.

 

Facts

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) manifesting bloody stools, severe diarrhea, and frequent abdominal pain, usually over time rather than suddenly, which is characterized by abnormal immune response, long duration, long-term inflammation and ulcer in the colonic mucosa. To the therapies currently available, many patients do not respond adequately or at all, seriously influencing their physical function, social and emotional health and work ability. It is estimated that 12.6 million people worldwide are suffering from IBD.

 

Pathopoiesis Mechanism

1. Sulfide in Diet

The toxic effect of sulfide on colon cells may be a major cause. The proportion of protein in diet increases as the adjustment of people's dietary habits, resulting in the sharply climbing intake of sulfur-containing amino acids (including methionine, cysteine, cystine and taurine). Through the degradation and fermentation of such amino acids by intestinal bacteria, a variety of sulfur-containing compounds are produced. The accumulation of hydrogen sulfide in the intestine may have a certain direct toxic effect on colon cells, and may also indirectly change the protein function and antigenicity. Research shows that the intake of meat (rich in protein), especially red meat and processed meat, increases the risk of UC recurrence. In addition, due to the non organic sulfate (including sulfur dioxide, hydrogen sulfide, sulfite) is widely used as preservative in the storage and storage of food and beverage, such as hamburger, concentrated beverage, sausage, beer and red wine, etc. Therefore, these foods and drinks also increase the risk of UC.

 

2. Dietary Fat

Excessive intake of fat or unsaturated fatty acid will damage the colonic mucosa, result in colitis, and may also affect the absorption and secretion of cholesterol. The hypercoagulable state formed by hypercholesterolemia can cause vasospasm, increase the tension of blood vessels, and affect the blood supply of mucosa, which therefore may cause colon mucosa damage. Excessive intake of monounsaturated fatty acids and polyunsaturated fatty acids may increase the incidence of UC.

 

3. Carbohydrate

High sugar intake may be related to UC. According to an epidemiological survey, people who often eat foods with high sugar content, such as cola drinks and chocolate have a positive correlation with UC, compared with those who jointly eat vegetables and fruits. The pathogenesis of UC caused by high sugar diet is not clear so far.

 

Diagnosis

Conventional approaches of UC diagnosis like clinical evaluation (symptoms), radiology and endoscopy, in conjunction with histological examinations and imaging techniques are costly and time-consuming. Non-invasive diagnostic tests on serological biomarkers (p-ANCA, ASCA, CBir1, anti-I2, etc.) and stool markers (infectious pathogens like calprotectin and lactoferrin) in easily obtained biological samples with IVD immunoassays are receiving popularity recent years, which have been well developed into various platforms, including ELISA, LFIA, CLIA, IHC, etc.

 

In March 2020, Zeposia was approved by the U.S. FDA for the treatment of adult multiple sclerosis (clinically isolated syndrome, recurrent remission disease and active secondary progressive disease), which in May got approved by the European Commission to treat adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease manifesting clinical or imaging characteristics.

 

UC is an unpredictable and potentially debilitating disease. The results of the True North study are very encouraging for patients with moderate to severe UC due to the consistent efficacy at key clinical and endoscopic endpoints, suggesting that Zeposia may address the need for new oral therapies.


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