Although the U.S. Food and Drug Administration has not approved methotrexate for scleroderma, the European League against Rheumatism and the British Society of Rheumatology and British Health Professionals in Rheumatology support its use for treating skin symptoms in the early stages of diffuse systemic scleroderma.
How methotrexate works in scleroderma
Patients with scleroderma have a chronically switched-on immune system. This causes high levels of inflammation that lead to scar tissue building up in the skin. The build-up can also affect the heart, lungs, and a number of other organs.
Methotrexate works by blocking the production of a molecule called folinic acid, which plays an important role in DNA and protein production. When a person takes methotrexate, cells that usually divide rapidly — like those in the immune system — are unable to multiply as fast because the drug limits their ability to make new DNA and protein. The result is that methotrexate can control excessive inflammation in the body.
Methotrexate in clinical trials for scleroderma
A global clinical trial (NCT02339441) called the European scleroderma observational study compared the effectiveness of methotrexate and other medications in 326 patients. The trial took place at 50 centers in Europe, North America, the Middle East, and Australia.
Sixty-five patients received 20 to 25 mg of methotrexate a week, while 118 received up to 1 g of CellCept (mycophenolate mofetil) twice a day, and 87 received cyclophosphamide. The cyclophosphamide dose was either a 500 mg/m2 injection every month or a 1-2 mg pill every day. All three medications are immunosuppressants.
Another group of 56 patients did not receive any immunosuppressants for their scleroderma, although some were on steroid treatments.
Those who were on any of the three immunosuppressants had better skin symptoms at the end of two years, compared with the group who did not receive them. Another finding was that none of the immunosuppressants outperformed the others.
A Phase 1/2 clinical trial (NCT00241189) generated similar results. It compared methotrexate and rapamycin in 18 diffuse systemic scleroderma patients. The methotrexate group took 20 mg a day orally, and the rapamycin group 6 mg a day for a year.
Both treatments were effective at reducing the symptoms of scleroderma, researchers found. The therapies’ side effects were also similar.
A small, randomized, double-blind year-long trial looked at whether low doses of injected methotrexate — 15 to 25 mg a week — would benefit systemic sclerosis patients. It did a better job of improving skin symptoms, finger grip strength, and general well-being than a placebo, researchers found.
Common side effects of methotrexate include nausea, vomiting, hair loss, mouth ulcers, headaches, fatigue, and a decreased sense of well-being. Folic acid supplements are often taken with methotrexate to help counter the medication’s side effects.
Methotrexate can also cause the same kind of interstitial lung disease that scleroderma can. In addition, it can cause liver problems and a reduction in all types of blood cells — a condition known as pancytopenia. Doctors need to monitor patient closely for signs of the more serious side effects the medication can generate.
Women taking methotrexate who plan to have a child should discuss this with their doctor because it can harm a fetus and lead to miscarriages.
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