Overview: Immunomodulators are typically considered when patients aren’t achieving remission with steroids, aminosalicylates, or antibiotics. If your disease is severe, you may be offered immunomodulators as a first-line therapy.
Immunomodulators decrease the number of inflammatory cells in your body, including strongly inhibiting white blood cells. They are used to treat other autoimmune conditions as well as prevent rejection of transplanted organs and certain cancers. Immunomodulators are steroid-sparing and are often used to help patients wean off steroids when they would not otherwise be able to because of severe symptoms. They are especially helpful for inflammation induced complications like fistulas in Crohn’s patients.
Types:
- Thiopurines
- Class of drugs that mimics the building blocks of DNA. Since they look similar, cells will try to use them but when they do the DNA-making process is altered or delayed.
- Common drugs include Azathioprine and 6-mercaptopurine (6-MP)
- 6-MP is the active form that actually works to reduce inflammation
- Azathioprine is converted to the active form in the body (same method as 6-MP, just requires one more step of conversion)
- Methotrexate
- Methotrexate mimics folic acid, an essential molecule used to create DNA in cells. Because it mimics folic acid, when methotrexate is incorporated into DNA-producing machinery, cell multiplication is blocked.
- Cyclosporine and tacrolimus
- These restrict the production of inflammatory cytokines by T-cells, special white blood cells that help protect the body from infection.
How do they work?
- They work on the DNA of cells to decrease the amount of inflammatory white blood cells circulating in the body. DNA is used by every cell in the body and every time a cell is multiplied or divided, the DNA is copied. White blood cells use a lot of DNA to multiply very quickly. So, by targeting the DNA immunomodulators slow down white blood cells ability to multiply, which is what causes the tissue damage in IBD.
- Disrupting the system and slowing down the rate of white blood cell production is helpful, but it also acts in the same way in other cells which is why side effects are seen. Lowering white blood cells also lowers the patient’s ability to fight infections.
- These drugs are very effective, but are slow acting. It may take 2-4 months to see full benefits, so your doctor may utilize another short-term drug if symptoms are severe.
When are they used?
- Moderate-severe Crohn’s and colitis
- If the patient fails to respond to aminosalicylates, steroids, or antibiotics
- Not routinely used to treat mild disease
- For those having trouble weaning off steroids because symptoms are severe or recurring
- Thiopurines: require months of treatment, see best results between 3-6 months, typically used long-term and taken in pill form by mouth
- Methotrexate: injectable form is more commonly used to treat IBD, although an oral form exists. A doctor or nurse typically administers the shot once a week under the skin or into the muscle. Some patients may administer themselves.
- Cyclosporine: used in rare cases to treat severe colitis, usually IV form to get adequate levels into the bloodstream quickly. Once a desired level is reached, an oral form is typically used. Cyclosporine is usually used in the short-term (a few months) while other less toxic drugs start working.
- Tacromillus: used even more rarely in difficult and tough cases of Crohn’s and colitis. More studies are needed before it is widely accepted and used.
Side effects:
- Common side effects of Azathioprine/6-MP:
- Decreased white blood cell count
- Increased risk of infection
- Nausea and vomiting
- Increased liver enzymes
- Muscle ache
- Less common side effects of Azathioprine/6-MP:
- Hair loss
- Abdominal pain
- Pancreatitis, which caused abdominal pain, nausea and vomiting
- Lymphoma
- Common side effects of methotrexate:
- Nausea
- Fatigue
- Skin rash
- Decrease in sperm count and possible birth defects in babies (people must wait 3 months after stopping methotrexate before trying to conceive)
- Diarrhea
- Decreased white blood cell count
- Less common side effects of methotrexate:
- Dizziness
- Liver toxicity
- Joint pain
- Kidney and lung toxicity
- *Note: Women who are pregnant or may become pregnant cannot use methotrexate. It can cause severe birth defects or miscarriages. Women of childbearing age who are taking this drug should use two forms of birth control.