Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) at a glance

IBD is an umbrella term for a few different chronic diseases that cause inflammation in the gastrointestinal tract (GI) tract. Ulcerative colitis (UC) and Crohn’s disease, the most common types of IBD, affect up to three million people in the United States and about 10 million globally, and the prevalence of IBD is expected to continue to grow in the coming years.

Symptoms of IBD include diarrhea, cramping, abdominal pain, rectal bleeding, loss of appetite and weight, and over the long term, increased risk for development of colorectal cancer.

Existing treatments for ulcerative colitis (UC)

UC is a chronic disease that often begins in adolescence or young adulthood, and generally requires patients to advance through several different treatments over a lifetime. Treatment for UC typically follows a step-up progression.

The first line of treatment for induction and maintenance is generally a 5-aminosalicylate (5-ASA) drug, such as mesalamine. These agents are viewed as relatively safe, but they fail to keep a significant proportion of patients in remission over the long term. Corticosteroids such as prednisone are commonly prescribed for exacerbations of disease. Although corticosteroids are effective at controlling these exacerbations, side effects associated with their long-term use limit treatment duration and require use of additional immunosuppressants as maintenance treatments. Patients who are not well controlled on 5-ASA drugs and steroids may progress to conventional immunosuppressive drugs such as azathioprine and methotrexate.

For some patients who fail to maintain remission on these immunosuppressant agents, or for many patients directly after 5-ASA failure, treatment progresses to biologic agents such as anti-tumor necrosis factor inhibitors, T-cell trafficking modulators, and interleukin-12/23 inhibitor drugs, and then to drugs in novel small-molecule classes such as Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) receptor modulators. These drug classes induce clinical remission in only a minority of patients and initial clinical responses are often lost over time. In addition, some of these drugs are associated with adverse events that include serious infections and lymphoma.

Microbiome alterations in IBD

Despite progress in understanding IBD pathways, what causes the disease has not been clearly established. The most widely accepted view is that IBD results from altered interactions between the gut microbiota and the immune system in genetically susceptible hosts.

Existing advanced treatments for IBD focus on suppressing the immune system and ignore the role of the gut microbiome in driving disease pathogenesis. In contrast, Vedanta’s approach to IBD targets the altered balance of gut bacteria that we believe is a driver of the disease.