Immunomodulators

Immunomodulators (IMs), also known as immunosuppressants, are medications that can be used as a treatment option for people living with inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis.1 These conditions cause chronic, long-lasting inflammation within the digestive tract, which in turn can cause symptoms affecting anywhere from the mouth to the anus, as well as outside of the digestive tract.

Many medications used to treat people with IBD, including IMs, work by reducing the inflammation in the digestive tract that causes the symptoms. Reducing the symptoms over time can lead to a period of remission for many patients. The goal of using IM medications to treat IBD by reducing inflammation is to help patients by:

  • Improving their symptoms
  • Helping them to enter periods of remission
  • Helping their remission periods to last longer1

How do immunomodulators work?

Each type of immunomodulator medication contains a specific kind of active ingredient that works by changing the way that the immune system carries out its functions in a person’s body. Some of these drugs work by suppressing or weakening the immune system, and others by modifying the way it works in different ways.1

Inflammation in the body is a standard immune system response to infection or disease within the body. Researchers think that in people with IBD, the immune system may be overactive in a way that causes excessive inflammation in a person’s digestive tract. This means that people with CD or ulcerative colitis have an immune system that mistakenly looks at the digestive tract, or parts of it, as a foreign object that needs to be attacked. This triggers inflammation, which is the body’s natural protective response to a foreign object or infection. However, for people with IBD, this inflammation is chronic and damaging because the immune system is constantly trying to attack its own digestive tract (the perceived “foreign object”). For this reason, immunomodulators can be effective in reducing inflammation and improving symptoms for many people with IBD.

What kinds of immunomodulators are used to treat inflammatory bowel disease?

Immunomodulators have been used to treat people with IBD for more than 50 years.1-3 Immunomodulators can also be called “immunosuppressants.” Five types of IM medications are regularly used to treat people with IBD:

  • azathioprine (brand name: Imuran)
  • 6-mercaptopurine (6-MP) (brand name: Purinethol)
  • cyclosporine (brand names: Gengraf, Neoral, Sandimmune)
  • tacrolimus
  • methotrexate (brand name: rheumatrex)

Immunomodulators are most commonly used to treat patients with IBD that is moderate or severe. There are several kinds of situations in which a person with IBD might try treatment with immunomodulator. If a person has tried treatment with aminosalicylates, antibiotics, or corticosteroids, but they did not work well enough to reduce the IBD symptoms, then healthcare providers may recommend trying an immunomodulator. Immunomodulators may also be recommended for patients who have fistulas, or who have symptoms located around the anus (perianal disease) that do not respond to treatment with other types of medications. Perianal disease can be very severe and painful, so patients will often try treatment with different types or combinations of medicines, such as antibiotics, corticosteroids, and/or aminosalicylates. If those do not relieve the person’s symptoms well enough, they may try treatment with immunomodulators. Immunomodulators can also be prescribed to help prevent IBD from flaring up again after surgery.

Some immunomodulators (azathioprine and 6-mercaptopurine) are long-term treatments for IBD, because sometimes people have to take them for as many as 3 to 6 months before they experience improvements in their symptoms. Others (cyclosporine, tacrolimus, and methotrexate) generally take effect more quickly, often within a couple of weeks.

What is the relationship between corticosteroids and immunomodulators?

Because immunomodulators can take a long time to start working, sometimes healthcare providers will recommend that patients start taking a corticosteroid at the same time they start taking the immunomodulator.1,2 This is because corticosteroids generally take effect more quickly in improving a person’s symptoms.

Corticosteroids can cause many different side effects, some of which can be very serious. Some people who take corticosteroids can also become physically dependent on them because of how much it alters the body while a person is on this type of medication. This means that many patients with inflammatory bowel disease may experience a flare up when they stop taking them. One of the benefits of immunomodulators for some patients is that they stay in remission longer, which means that they do not need to use corticosteroids to treat flares as often.4

What are some common side effects linked to immunomodulator treatment?

Various forms of immunomodulators can cause different side effects. However, some common side effects include:1

  • Headache
  • Nausea
  • Vomiting
  • Diarrhea

Immunomodulators work by suppressing or weakening a patient’s immune system in order to reduce inflammation and the symptoms it causes. However, they can also have the effect of decreasing the body’s ability to combat infection. Patients taking immunomodulators should contact their healthcare provider if they begin to experience fever or chills, as these could be signs of an infection. People taking immunomodulators are also more likely to catch infections like a cold or the flu, because the medicine is telling their immune systems not to trigger inflammation to fight any infections or foreign objects. While this can help relieve the symptoms of IBD, it can also make it easier for infections to take hold.

Some patients experience decreased function of the kidney or liver if they take some forms of immunomodulators over the long term. For a small number of patients, certain immunomodulators can cause other very serious side effects. For this reason, healthcare providers will take extensive medical histories before prescribing immunomodulators and then carefully monitor patients for any signs of these effects.

As with any prescription medication, patients should be sure to consult their healthcare providers about all potential forms of treatment and any possible drug interactions. Women who are pregnant or planning to become pregnant should be sure to let their healthcare providers know before beginning treatment with immunomodulators, because some types can cause pregnancy loss or possible birth defects.

Written by: Anna Nicholson and Emily Downward | Last Reviewed: January 2018.
View References
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  1. Immunomodulators, Crohn’s & Colitis Foundation of America. Available at: http://www.crohnscolitisfoundation.org/resources/immunomodulators.html. Accessed 1/18/18.
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  3. Knutson D, Greenberg G, Cronau H. Management of Crohn's disease--a practical approach. Am Fam Physician. 2003;68:707-714.
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  5. Siegel, CA. Safe and Effective Use of Immunomodulators for Inflammatory Bowel Disease. Practical Gastroenterology 2006;7:31-44.
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  7. Corticosteroids, Crohn’s & Colitis Foundation of America. Available at http://www.crohnscolitisfoundation.org/resources/corticosteroids.html. Accessed 1/18/18.