Methotrexate is a cytotoxic, or cell-killing, agent approved by the U.S. Food and Drug Administration (FDA) to treat various cancers, adults with severe psoriasis and severe rheumatoid arthritis.

It may be used as a treatment option for sarcoidosis, an inflammatory disease in which clumps of immune cells called granulomas form in different tissues and organs, interfering with their function. Methotrexate targets fast-growing cells like those of the bone marrow cells (which produce immune cells), cancer, and skin.

How methotrexate works

Methotrexate inhibits the activity of an enzyme called dihydrofolate reductase (DHFR), which is vital for the synthesis of DNA. When cells duplicate, they make a complete copy of their genome before dividing into two new cells. The faster a cell duplicates, the more DNA it needs to make. Blocking the DHFR enzyme affects cell division, especially in fast-growing cells.

In sarcoidosis, methotrexate can slow the growth of immune cells to lower immune system sensitivity and reactivity. It is used as an alternative to corticosteroids such as prednisone, especially in patients who fail to respond well to them.

Methotrexate in clinical trials for sarcoidosis

One study, published in the scientific journal Advances in Respiratory Medicine, reported results from 50 patients with chronic progressive pulmonary sarcoidosis treated solely with methotrexate(10 mg or 15 mg once a week) for six to 24 months. Data showed that the treatment led to improvements in the lung function and X-ray scans in 55 percent of these patients, with best results in the higher-dose group. Eleven patients stopped taking methotrexate due to side effects, and mild liver abnormalities were reported in 10 patients.

An ongoing clinical trial (NCT02356445) is evaluating retrospectively the outcomes of some 2,000 sarcoidosis patients using cytotoxic or other immunosuppressive medications: methotrexate, Imuran (azathioprine), infliximab, or Acthar. Researchers will record and analyze how many patients show clinical improvement based on computerized tomography (CT) scans, and the number of adverse events reported while under treatment. This trial, run by University of Cincinnati researchers, is set to conclude in December 2018.

Additional information

For sarcoidosis, methotrexate is usually used at lower doses than in cancer patients, and side effects are usually less severe. Many doctors will also recommend a folic acid supplement to minimize treatment side effects.

Nausea, tiredness, and immune suppression are the most common side effects of methotrexate. Because the medicine may cause liver and kidney damage, close monitoring by a physician is required while using methotrexate. The treatment cannot be taken by women who are pregnant or breastfeeding.


Sarcoidosis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.