Immunomodulators for inflammatory bowel disease

Examples

How It Works

Immunomodulator medicines, such as azathioprine (AZA), 6-mercaptopurine (6-MP), and methotrexate, weaken or suppress the immune system.

These medicines are used most often to prevent the body from rejecting a newly transplanted organ, but they are also helpful in treating inflammatory bowel disease (IBD).

Why It Is Used

Immunomodulators are used for inflammatory bowel disease (IBD) that:

• Has not responded to other treatments.
• Can be controlled only with long-term use of corticosteroids. Immunomodulators may be used so that the doctor can lower the dose of corticosteroids that a person is taking. This is called "steroid sparing."

How Well It Works

Immunomodulator medicines are effective against inflammatory bowel disease. AZA and 6-MP are used to maintain remission (a period without symptoms) in ulcerative colitis and Crohn's disease. Both medicines are effective in treating fistulas in Crohn's disease.

Crohn's disease

It may take 4 months or more for azathioprine (AZA) and 6-mercaptopurine (6-MP) to improve symptoms. These medicines are used to keep a person in remission and allow the person to stop using corticosteroids. These are the most commonly used immunomodulators. They usually work well, but the disease often comes back after you stop taking the medicine.¹ Methotrexate improves symptoms more quickly than 6-MP, but it has not been studied as extensively.

A few studies have shown that methotrexate stops the symptoms of Crohn's disease and keeps the disease in remission.¹ Usually, methotrexate is used when azathioprine (AZA) and 6-mercaptopurine (6-MP) don't work.

Tacrolimus can be used in Crohn's disease when corticosteroids do not work or fistulas develop. It also may be applied topically for Crohn's disease that affects the mouth or perineal area.²

Mycophenolate mofetil has been studied in active Crohn's disease, with mixed results. More research is needed to confirm its role.³

Thalidomide has been shown to work in Crohn's disease when corticosteroids did not. It has also been used to treat fistulas. Controlled studies still need to be done. There is some worry about serious side effects of thalidomide.¹

Ulcerative colitis

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are used for moderate to severe ulcerative colitis to keep symptoms of the disease from coming back after a person has reached a period without symptoms (remission).

Azathioprine has been shown to keep 80% to 90% of people in remission for over 2 years. It also allows people to stop taking corticosteroids.⁴

Oral azathioprine (taken by mouth) is used with steroids or cyclosporine for moderate or severe colitis. Using azathioprine to maintain remission in this way reduces the chances that symptoms will come back. It also makes it less likely that a person will need a colectomy.⁴

Side Effects

Side effects of immunomodulator medicines include:

• Nausea, vomiting, diarrhea, or stomach ulcers.
• Rash.
• General feeling of being ill (malaise).
• Liver inflammation.

Rare side effects include:

• Suppression of blood cell production (bone marrow suppression), which may increase the risk of infection or serious bleeding. Return to normal blood cell production may take several weeks after the medicine is stopped.
• Fever.
• Inflammation of the pancreas (pancreatitis). This may occur with AZA and 6-MP.

Extremely rare side effects of azathioprine include a possible increased risk of cancer. Mycophenolate mofetil may increase the risk of cancer of the lymph system (lymphoma) and other types of cancer.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Regular blood tests are needed to check for effects that these medicines may have on the bone marrow, liver, and kidneys.

Immunomodulator medicines are less likely than corticosteroid medicines to cause growth failure in children.

Since these medicines weaken or suppress the immune system, they increase your risk of infection.

If you are pregnant or want to become pregnant, talk to your doctor about whether you can take immunomodulator medicines. Some of these medicines are used in pregnancy but only when the benefit outweighs the potential risk of harm to the fetus. Methotrexate, mycophenolate mofetil, and thalidomide should not be used because they can cause birth defects and pregnancy loss.

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.

References

Citations

1. Friedman S, Lichtenstein GR (2006). Crohn's disease. In MM Wolfe et al., eds., Therapy of Digestive Disorders, 2nd ed., pp. 785-801. Philadelphia: Saunders Elsevier.

2. Sands BE (2006). Crohn's disease. In M Feldman et al., eds., Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 8th ed., vol. 2, pp. 2459-2498. Philadelphia: Saunders Elsevier.

3. Hanauer SB, Dassopoulos T (2001). Evolving treatment strategies for inflammatory bowel disease. Annual Review of Medicine, 52: 299-318.

4. Friedman S, Lichtenstein GR (2006). Ulcerative colitis. In MM Wolfe et al., eds., Therapy of Digestive Disorders, 2nd ed., pp. 803-817. Philadelphia: Saunders Elsevier.

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