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Clinical Trials Investigate New Therapies for Crohn's Disease

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Crohn's Disease can be managed

Crohn’s disease is a chronic condition that involves inflammation of the digestive tract. Although it can affect any part of the digestive tract from the mouth to anus, it most commonly affects the distal part of the small intestine and the beginning of the colon. It is a type of inflammatory bowel disease (IBD), the other types of IBD being ulcerative colitis and microscopic colitis.

Crohn’s disease is characterized by flares with intervals of remission. The pathogenesis of Crohn’s disease is unknown, but researchers suspect that autoimmune reactions, where the immune system attacks the body’s own healthy cells, could be one cause. The pathogenesis is thought to be due to a combination of factors including immune system alterations, genetics, environmental factors, and microbiome changes. Some risk factors for developing this disease include family history, smoking, consuming a high-fat diet, and some medications such as birth-control pills, antibiotics, and some nonsteroidal anti-inflammatory drugs (NSAIDS) like aspirin.

The most common symptoms of Crohn’s disease include abdominal pain or cramping, diarrhea, and weight loss. The symptoms often differ, depending on the severity and where along the digestive tract it occurs. Patients may present with other symptoms such as fatigue, joint pain, fever, anemia, loss of appetite, and nausea. Other problems that may arise due to Crohn’s disease are fistulas, abscesses, intestinal obstruction, anal fissures, ulcers, malnutrition, and inflammation in areas other than the digestive tract, such as the eyes, skin, and joints.

Diagnosing Crohn’s Disease

There is no specific diagnostic test for Crohn’s disease. Physicians often only diagnose Crohn’s disease after ruling out other possible causes for the symptoms. In order to make a diagnosis, the physician would carry out a thorough investigation including symptom inquiry, taking family and medical history, conducting a physical examination including the palpation, auscultation, and percussion of the abdomen.

Various tests may be conducted to help diagnosis such as:
  • Blood and stool tests
  • Colonoscopy
  • Upper GI endoscopy
  • Diagnostic imaging, most commonly a CT scan with contrast enhancement (patients may be asked to drink barium which allows better visualization of the upper GI tract).
  • Biopsy, or taking a tissue specimen, during an endoscopy or colonoscopy.
 

Managing Crohn’s Disease

Although there is no definitive cure for Crohn’s disease, treatments are available that can help reduce intestinal inflammation, relieve symptoms, and prevent potential complications. These treatments include bowel rest, medications, and surgery. Medical treatment is often tailored to the disease location, severity, subtype, and behavior. Other factors like lesion extension, age at diagnosis, and extra-intestinal manifestations are also considered.

Many drugs are used in Crohn’s disease but are not curative. These drugs mainly target decreasing inflammation and minimize symptoms. Among the drugs used is Mesalazine which has been shown to induce and maintain remission in patients with Crohn’s disease. Antibiotics like fluoroquinolones and metronidazole are also used and primarily treat septic complications such as in the case of perianal fistulas. Other important medications are immunosuppressants such as methotrexate and thiopurines which are used to maintain remission and are often used in combination with steroids.

One of the most effective medications for moderate and severe forms of Crohn’s disease are anti-TNF drugs. They may be used alone or in combination with immunosuppressants to induce and sustain remission. The most commonly used anti-TNF drugs are infliximab, adalimumab, and certolizumab. Recently, highly selective monoclonal antibodies that target specific patterns of inflammation were developed. These include vedolizumab, which inhibits leukocyte migration, and ustekinumab, an interleukin inhibitor.

Many surgical strategies have been developed to improve the outcome of Crohn’s disease. Surgery is mainly aimed at treating complications and symptoms after other treatments have shown to be unsuccessful. Up to 75 percent of patients eventually undergo surgery. Surgery for Crohn’s disease involves removing damaged areas of the digestive tract to treat complications such as intestinal obstruction, fistulas, severe bleeding, side-effects from medications, and symptoms that are not relieved by other treatments.

Physicians may also advise patients to alter certain lifestyle habits and make dietary changes. This includes avoiding overeating, consuming smaller portions of food with shorter intervals between meals, increasing fluid intake, avoiding high fiber foods and carbonated drinks, and keeping a food diary to help identify problematic foods.

Newer therapies for Crohn’s Disease

A potential treatment for Crohn’s disease is xanthohumol, an isolate from the hop plant that has demonstrated anti-inflammatory properties. The use of xanthohumol for Crohn’s disease is currently under clinical trial in the United States after studies have shown it to inhibit production of oxidative stress and pro-inflammatory cytokines.

Another investigational therapy is autologous stem cell transplant. Clinical trials are currently being conducted in the United States to investigate the effectiveness of stem cell therapy for treatment-refractory, severe Crohn’s disease. To improve success, transplant is combined with pharmaceutical therapy to increase chances of remission. The suggested mechanism by which patients can reach remission is through ablation of inflammatory cells by chemotherapy followed by stem cell transplant, marrow reconstitution, and restoration of the immune system.

An additional treatment under clinical trial is the drug ustekinumab. Its therapeutic role involves decreasing immune cell activation by preventing cytokine-receptor binding. Studies have demonstrated it to be effective in potentially treating moderate and severe Crohn’s disease, psoriatic arthritis, and psoriasis.

 

Resources:
  • Petagna L, Antonelli A, Ganini C, et al. Pathophysiology of Crohn's disease inflammation and recurrence. Biol Direct. 2020;15(1):23. Published 2020 Nov 7. doi:10.1186/s13062-020-00280-5
  • Simon EG, Ghosh S, Iacucci M, Moran GW. Ustekinumab for the treatment of Crohn's disease: can it find its niche?. Therap Adv Gastroenterol. 2016;9(1):26-36. doi:10.1177/1756283X15618130
  • Cho JM, Yun SM, Choi YH, et al. Xanthohumol prevents dextran sulfate sodium-induced colitis via inhibition of IKKβ/NF-κB signaling in mice. Oncotarget. 2017;9(1):866-880. Published 2017 Dec 12. doi:10.18632/oncotarget.23183
  • Brierley CK, Castilla-Llorente C, Labopin M, et al. Autologous Haematopoietic Stem Cell Transplantation for Crohn's Disease: A Retrospective Survey of Long-term Outcomes From the European Society for Blood and Marrow Transplantation. J Crohns Colitis. 2018;12(9):1097-1103. doi:10.1093/ecco-jcc/jjy069
  • Crohn’s Disease. Medlineplus.gov. Published 2019. https://medlineplus.gov/crohnsdisease.html
  • Holland K. Understanding Crohn’s Disease. Healthline. Published August 22, 2018. https://www.healthline.com/health/crohns-disease#diet

     

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This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician. All readers/viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. CenTrial Data Ltd. does not take responsibility for possible health consequences of any person or persons reading or following the information in this educational content. Treatments and clinical trials mentioned may not be appropriate or available for all trial participants. Outcomes from treatments and clinical trials may vary from person to person. Consult with your doctor as to whether a clinical trial is a suitable option for your condition.