Crohn‘s disease is a chronic inflammatory condition that causes inflammation, or swelling, and irritation of any part of the digestive tract— also called the gastrointestinal tract (GIT). In some people with Crohn’s disease, only the last segment of the small intestine (ileum) is affected. In others, the disease is confined to the colon (part of the large intestine). The most common areas affected by Crohn’s disease are the last part of the small intestine and the colon. Signs and symptoms of Crohn’s disease can range from mild to severe. They usually develop gradually, but sometimes will come on suddenly, without warning. You may also have periods of time when you have no signs or symptoms (remission). More than a half million Americans have been diagnosed with Crohn‘s disease. Crohn’s disease–related inflammation is segmental and transmural, leading to various degrees of tissue damage. At disease onset, most patients have inflammatory lesions, which become predominantly strictures or penetrating lesions over time.
Ulcerative colitis is a chronic disease that affects about 620,000 Americans. It causes inflammation and ulcers in the inner lining of the large intestine and is one of two main forms of chronic inflammatory bowel disease. The inflammation can lead to abdominal discomfort, gastrointestinal bleeding, and diarrhea.
“Ulcerative colitis and Crohn‘s disease are debilitating diseases that impact the quality of life of those who have these conditions,” said Amy G. Egan, M.D., M.P.H., acting deputy director of the Office of Drug Evaluation III in the FDA‘s Center for Drug Evaluation and Research.
When the disease is active, signs and symptoms may include:
- Abdominal pain and cramping
- Blood in your stool
- Reduced appetite and weight loss
- Fever and fatigue
- Mouth sores etc.
People with severe Crohn’s disease may also experience:
- Inflammation of skin, eyes and joints
- Inflammation of the liver or bile ducts
- Delayed growth or sexual development, in childrenAnti-inflammatory drugs are often the first step in the treatment of inflammatory bowel disease. These include: Azathioprine and mercaptopurine – These are the most widely used immunosuppressants for treatment of inflammatory bowel disease. Short term, they also can be associated with inflammation of the liver or pancreas and bone marrow suppression. Long term, although rarely, they are associated with certain infections and cancers including lymphoma and skin cancer. They may also cause nausea and vomiting.Methotrexate – This drug, which is used to treat cancer, psoriasis and rheumatoid arthritis, is sometimes used for people with Crohn’s disease who don’t respond well to other medications.
- Infliximab, adalimumab and certolizumab pegol – These drugs, called TNF inhibitors or “biologics,” work by neutralizing an immune system protein known as tumor necrosis factor (TNF). They are used for adults and children with moderate to severe Crohn’s disease to reduce signs and symptoms. They also may induce remission. Researchers continue to study these drugs to compare their benefits.
- Corticosteroids – A newer type of corticosteroid, budesonide works faster than do traditional steroids and appears to produce fewer side effects. However, it is only effective for Crohn’s disease that’s in certain parts of the bowel.
- Oral 5-aminosalicylates — These drugs have a number of side effects, including nausea, diarrhea, vomiting, heartburn and headache. These drugs have been widely used in the past but now are generally considered of limited benefit.
- Treatment for Crohn’s disease usually involves drug therapy or, in certain cases, surgery. There is currently no cure for the disease, and there is no one treatment that works for everyone. By reducing the inflammation that triggers your signs and symptoms, it improves long-term prognosis by limiting complications. In the best cases, this may lead not only to symptom relief but also to long-term remission.
Vedolizumab (Entyvio ): It is approved to treat those conditions when one or more standard therapies have not resulted in an adequate response. The recommended dosage of vedolizumab in adults with ulcerative colitis or Crohn’s disease is 300 mg administered by intravenous infusion over 30 min at zero, two and six weeks and then every eight weeks thereafter.
Similar pharmacokinetics were observed in ulcerative colitis and Crohn’s disease patients administered 300 mg vedolizumab as a 30 minute intravenous infusion on Weeks 0 and 2, followed by 300 mg vedolizumab every eight weeks starting from Week 6. Population pharmacokinetic analyses indicated that the linear clearance was approximately 0.157 L/day, the serum half-life was approximately 25 days at 300 mg dosage, and the distribution volume was approximately 5 L.
The safety and effectiveness of vedolizumab for Crohn‘s disease were established in three clinical trials involving approximately 1,500 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. Results showed that a greater percentage of participants treated with Entyvio compared to a placebo achieved clinical response, achieved clinical remission, and achieved corticosteroid-free clinical remission.
Mongersen, an Oral SMAD7 Antisense Oligonucleotid; is a formulation containing a 21-base single-strand phosphorothioate oligonucleotide that hybridizes to the human SMAD7 messenger RNA (mRNA) and facilitates RNase H–mediated RNA degradation through a classic antisense mechanism. Mongersen is a modified-release tablet, designed to deliver the active substance primarily into the lumen of the terminal ileum and right colon.
Pharmacokinetic analysis of plasma before and after treatment suggested that mongersen was not systemically available. Drug acts locally, no systemic exposure. Therefore, it has better define the efficacy and safety for treating adults with active Crohn’s disease. The researchers found that 55 and 65% of patients in the 40mg and 160mg mongersen groups, respectively, reached the primary end point, compared with 10% of patients in the placebo group.