Andrew DuPont, MD and Atilla Ertan, MD
Crohn’s disease is a chronic inflammatory bowel disease (IBD) that is suspected to result from a dysregulated immune system in genetically predisposed individuals, which can lead to abdominal pain, diarrhea, and malnutrition. Intestinal inflammation and subsequent symptoms tend to recur over time and can lead to other complications, such as fistulas, abscesses, and strictures.
Previously, only limited treatment options existed; however, over the past 30 years, progress has been made regarding therapy. The goals of treatment include: healing inflammation, preventing recurrent inflammation and symptoms, reducing and eliminating the use of steroids, decreasing hospitalizations and surgical intervention, preventing complications and improving quality of the life.
Initially, treatment for Crohn’s disease consisted of corticosteroids, other anti-inflammatory medications (5-aminosalicylates), and often times surgery. Corticosteroids can reduce inflammation anywhere in the body, but are not effective for long-term treatment and have many significant side effects.
Other treatments have been developed more recently to directly suppress the immune response, rather than only treating inflammation, which is the result of the abnormal immune response. These medications include immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate) and biologic therapy (infliximab, adalimumab, certolizumab, and natalizumab), which are frequently used in combination. People who should be considered for early biologic therapy include: young age at disease onset, steroid use for initial flare, deep ulceration or fistulizing disease, multiple antibodies to intestinal flora, perianal disease, extensive disease in the upper small intestine, and no response to steroids after 2-4 weeks.
Infliximab (brand name, Remicade) was the first biologic medication approved for the management of Crohn’s disease. It is an antibody that attaches to a protein produced by the immune system called tumor necrosis factor (TNF) in the blood stream, which blocks its activity and leads to decreased inflammation. Infliximab consists of a partial mouse antibody that is modified to be more like a human antibody, which is given as an intravenous infusion over a period of at least 2 hours. It is initially infused 3 times over a 6 week period and if there is significant improvement, every 2 months for maintenance therapy. Infliximab is generally well tolerated; although, there can be reactions associated with the infusion. Because TNF is an important component of the immune system, infliximab and other biologic medications affect the body’s ability to fight infections, so people should be checked for tuberculosis and hepatitis B prior to starting these medications. It is also important to avoid live vaccines while taking these medications.
Adalimumab (brand name, Humira) is another anti-TNF agent similar to infliximab, which decreases inflammation by blocking TNF; however, adalimumab consists of a fully humanized anti-TNF antibody, and it is given in an injection under the skin. Adalimumab is given in 2 doses over a 2 week period and then every other week. It is also generally well-tolerated with the most common side effect being skin reactions at the site of the injection that may cause itching, redness, and swelling. Adalimumab has been shown to have similar effectiveness and safety when compared to infliximab for inducing and maintaining remission in patients with Crohn’s disease. It has also been shown to be effective for some people who have failed or cannot tolerate infliximab.
Certolizumab pegol (brand name, Cimzia) is a pegylated humanized antibody fragment that also acts by blocking the activity of TNF. It was approved for use in the US in 2008 for the treatment of moderate to severe Crohn’s disease in patients who do not respond sufficiently or adequately to standard medical therapy. Certolizumab also is a subcutaneous injection, similar to adalimumab, and is given twice over a 2 week period then once a month for maintenance therapy. It has been shown to be effective in inducing and maintaining remission in Crohn’s disease with similar adverse effects as seen with infiliximab and adalimumab.
Natalizumab (brand name, Tysabri) is a humanized monoclonal antibody to alpha-4 integrin, which acts by decreasing the binding of inflammatory cells (leukocytes) to the intestinal lining. It has been approved for moderate to severe Crohn’s disease that has not responded to other treatment. It is given as an infusion over 1 hour, once a month. Natalizumab should be used as monotherapy. Because it has been associated with a rare, but serious, brain infection (progressive multifocal leukoencephalopathy, PML), it is only available through a special restricted distribution program. Vedolizumab is a medication that also affects intestinal inflammation in a similar fashion, but the effect is specific to the intestine without the suspected risk of PML. It is expected that vedolizumab will soon be approved for the treatment of Crohn’s disease.
Biologic therapy with these available agents leads to clinical remission in approximately 30% and clinical response in 50% of patients with active Crohn’s disease. These agents have never been compared head-to-head, and the decision to start one or the other should be individualized. Newer medications continue to be developed and are evolving the way we treat Crohn’s disease.
Dr. Atilla Ertan earned his medical degree in 1963 from the Ankara University Medical School in Turkey. Following completion of his fellowship in Gastroenterology at the Hospital of the University of Pennsylvania in 1971, he was professor of medicine at the Tulane University School of Medicine in New Orleans from 1980-90 where he was named Chief of the Gastroenterology Section from 1984-90 and Interim Chairman of Medicine Department from 1988-90. Then, he was Chief of the Gastroenterology Section at the Methodist Hospital/ Baylor College of Medicine from 1990 to 2001. He is a Clinical Professor of Medicine at both Baylor College of Medicine as well as Weill-Cornell Medical College. He is now professor at the University of Texas Health Science Center at Houston and Medical Director of the Gastroenterology Center of Excellence and Digestive Disease Center at the Memorial Hermann Hospital-Texas Medical Center. Dr. Ertan has a special interest and experience in the diagnosis and management of patients with inflammatory bowel diseases including Crohn’s disease, ulcerative colitis, various microscopic colitides; biliary/pancreatic benign and malignant disorders, Barrett’s esophagus with dysplasia and early cancer plus these patients’ need for various advanced GI endoscopic diagnostic/therapeutic modalities.
Gastroenterology Center of Excellence
6400 Fannin, Suite 1400
Houston, Texas 77030