Immunomodulators calm the overly active immune response that leads to the inflammation that results in Crohn’s disease and ulcerative colitis. The immunomodulators used to treat IBD include 6MP, azathiorprine (Imuran), and methotrexate.

Immunomodulators were initially developed as treatments for cancer, but they have been used to treat IBD for decades, although at much lower doses than those used to treat cancer. Because of the long track record, we have a great deal of information about the safety and effectiveness of the immunomodulators.

Generic Brand name
6-MP (6-mercaptopurine) Purinethol
azathioprine Imuran
methotextrate Sold as a generic (predominantly used for Crohn’s disease)

How do immunomodulators work?

Immunomodulators work by suppressing the overly active immune response that occurs in IBD. 6MP and azathioprine (Imuran) are closely related drugs as azathioprine is converted into 6MP in the body.

How is it administered?

Both 6MP and azathioprine (Imuran) come in pill form and are administered orally. Azathioprine is given in larger doses than 6MP.

Methotrexate is usually given as a weekly injection. The injections are subcutaneous; they go into the fatty tissue under the skin. Methotrexate also comes in pill form and can be administered orally, but the rate at which is absorbed is variable, so dosing is difficult.

When will I feel better?

6MP and azathioprine (Imuran) are slow acting and can take from two to six months to reach their maximum effect. About 85% of people with ulcerative colitis have a clinical response (their condition improves) to 6MP or azathiorprine (Imuran). For people with Crohn’s disease, the clinical response rate to the two drugs is about 65%.

Some people experience relief of symptoms six to eight weeks after they start taking methotrexate. The full effect may not be experienced for several months.

Side effects

6MP and azathioprine (Imuran)

  • Increased risk for infection
  • Abnormal liver function
  • Pancreatitis
  • Decreased platelet counts
  • Nausea and vomiting
  • Rash
  • Diarrhea
  • Lymphoma (0.04%; average rate of population is 0.02%)

6MP and azathioprine (Imuran) put people at risk for infection because they decrease the number of white blood cells. If you are taking either of those two drugs, your white blood cell counts will be monitored closely so they don’t get too low and leave you defenseless against bacteria, viruses, and other sources of infection. A complete blood count (CBC), which includes a white blood cell count, is done every two weeks during the first months of treatment. Then CBCs are done monthly. If the counts are stable after a year, the tests are done less often. Dosing can be adjusted if the white blood cell counts get too low.


  • Nausea, vomiting, and loss of appetite
  • Elevated liver enzymes (15% of patients are affected)
  • Scarring of the liver (up to 7%)
  • Hair loss (0.5% to 10%)
  • Increased infection
  • Pneumonitis (1%)
  • Lymphoma

Possible drug interactions

Let your doctor know if you take any of the following medications:

  • ACE inhibitors (Lisinopril, Enalopril, Vasotec, Monopril, Uniretic, Zestoretic)
  • Allopurinol (Zyloprim)
  • Cyclosporine
  • Methotrexate
  • Anticoagulants (Coumadin, Heparin, Lovenox, Plavix)
  • Neuromuscular blockers (Tubocuranine, Pancuronium, Pavalon)

Additionally “live” vaccines should not be received while on immunomodulators.

How long do I need to take immunomodulators?

These immunomodulators can be highly effective in maintaining steroid-free remission in moderate-to-severe cases of IBD. Unlike steroids, these medications can be used safely for a long time and are designed to be taken as treatment to prevent and treat flares of your disease.

Many people with IBD take the immunomodulating medications for many years. It is important to take an immunomodulator medication even when you are feeling well and having few, if any, symptoms because they are preventive medications that keep flares from occurring.

Taking Immunomodulators while Pregnant

6MP and azathioprine (Imuran)

Women planning to become pregnant should discuss their treatment options with their care team. In most cases, women are advised to continue with maintenance immunomodulator treatment throughout pregnancy because an uncontrolled flare of your disease may be more harmful to the fetus than 6MP or azathioprine (Imuran).

Animal studies have shown no increase in adverse fetal effects from taking 6MP or azathioprine while pregnant.


Methotrexate is known to cause birth defects. You should not take this drug if you or your partner is planning on becoming pregnant.

Using two forms of birth control to avoid pregnancy while you are using this medicine and do so for at least 3 months after your treatment ends.

Call your care team immediately if you or your partner becomes pregnant if you are taking methotrexate or took it recently.