Why is methotrexate used to treat uveitis?
Uveitis is a general term used to describe inflammation inside the eye. There are different types of uveitis described by the location most affected in the eye. Uveitis is also separated by cause: infection or no infection. If an infection is found, antibiotics are prescribed. However, if there is no infection and the inflammation (uveitis) threatens loss of vision, medications are used to reduce the inflammation to protect the eye. Steroid medications are the first line of defense. Steroids work quickly and effectively in the short term. However, if the inflammation lingers, steroids may have unacceptable side effects to use long term. This is when medications like methotrexate are often used to quell inflammation and protect the vision with fewer side effects in the long term. Methotrexate is well-studied, safe, effective, and inexpensive. It is often the first drug used to minimize the need for steroids in treating uveitis. It is as effective as a more expensive drug in the same class called mycophenolate mofetil (FAST Trial).
How does methotrexate work?
Methotrexate works to suppress the immune system. The immune system includes white blood cells that are helpful to attack infections. However, sometimes the immune system attacks your own body and causes damage. Examples of this include rheumatoid arthritis, psoriasis, and uveitis. In these conditions it may be necessary to suppress the immune system enough to prevent damage to healthy tissues in the body. There are many different types of immunosuppressants; methotrexate is classified as an antimetabolite (like azathioprine and mycophenolate mofetil). Antimetabolites interfere with the production of DNA in rapidly dividing cells. However, this mechanism may not be the primary way methotrexate works to treat uveitis. It also suppresses the immune system by impairing lymphocyte (white blood cells) function. Although antimetabolites are effective in treating uveitis, there are not effective in treating joint disease in HLA B27.
How is methotrexate taken?
Methotrexate is taken weekly (on the same day of each week) by pill or subcutaneous injection. It is usually recommended by an ophthalmologist and prescribed by a rheumatologist. The role of the ophthalmologist is to help determine the optimal dose required to treat uveitis in a given patient. The rheumatologist monitors for side effects by examination and blood tests. Methotrexate may take up to six months to show its optimal benefits. During this time, other medications, like steroids, may be used to keep the uveitis under control.
What are the side effects of methotrexate?
Many side effects are possible, but they are generally reversible if detected early. Allergic reactions are rare, but should be reported to your doctor without delay. Common side effects include loss of appetite, upset stomach, tiredness, drowsiness, headache, diarrhea, and hair loss. Serious side effects may involve the liver (jaundice), lung (cough, shortness of breath), kidney (fluid retention, swelling), and the blood (bleeding). There are fewer sided affects with methotrexate compared with another commonly used antimetabolite, azathioprine (Galor 2008). At one time, there was concern that methotrexate might cause cancer. However, the SITE extension study (reported at AAO October 2022) showed that methotrexate actually reduces the risk of cancer among patients treated for uveitis.
What should a patient do while on methotrexate?
While on methotrexate do not become pregnant. Avoid alcohol as it may increase the risk of liver damage. Avoid live-virus vaccines (usually given in childhood). Report signs of infection to your doctor. Report side effect from methotrexate listed above. Take folic acid (also known as vitamin B9, Leucovorin) to reduce the side effects of methotrexate. Some recommend avoiding folic acid on the day of the week you take the methotrexate.
Your doctor has selected methotrexate to protect your vision. The benefits of treatment are felt to outweigh the potential risks. Do your part to make sure to take the medication exactly as prescribed and report problems without delay.
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