People whose psoriasis cannot be controlled by topical medications applied directly to affected areas of the skin may turn to systemic, or internally administered, drugs, to ultraviolet light treatments, to biologic therapies, or to some combination of them. In the United States, the three most common systemic medications for psoriasis are cyclosporine, methotrexate, and acitretin (Soriatane). This page discusses methotrexate.
Methotrexate (Rheumatrex and various generics)
What is it?
Methotrexate was developed as an anti-cancer drug and received FDA approval for the treatment of cancer in 1953. Not long afterward, doctors noticed that methotrexate also effectively controlled severe psoriasis and have prescribed it for that purpose ever since. The FDA officially approved methotrexate as a psoriasis treatment in the early 1970’s. Today, methotrexate is used to treat cancer and several immune system diseases, including psoriasis, psoriatic arthritis, rheumatoid arthritis and Crohn’s disease.
How is it administered? Methotrexate is typically taken in pill form, but it can also be administered by injection into the muscle, or intravenously. A typical dose would range from 10 mg to 25 mg weekly. Sometimes your physician will advise you to split the weekly dose into three segments taken over a 24-hour period (i.e., you take the first third of the total weekly dose, wait 12 hours, take the second third, wait 12 hours, then take the final third of the dose). As long as there are no signs of severe side effects, methotrexate can be taken for years. Some patients take a folic acid supplement along with methotrexate to reduce some of methotrexate’s side effects.
How well does it work?
Even though methotrexate has been used to treat psoriasis for decades, it has not been thoroughly tested for effectiveness in large clinical trials. But it was recently compared head-to-head with an experimental psoriasis treatment called briakinumab, and in that 52-week study, methotrexate helped a lot of psoriasis patients but could not reach the high levels the newer treatments are achieving. In the study, at 24 weeks, 40% of patients had achieved a 75% improvement in psoriasis symptoms; and 23% of patients had achieved a 90% improvement. At 52 weeks, those with a 75% improvement had fallen to 24% of methotrexate patients; and 18% were at a 90% improvement in psoriasis symptoms. Data from several small studies suggest that psoriasis improves by 50% (still a marked improvement for psoriasis patients) in approximately three-quarters of patients taking methotrexate. And in a study that compared cyclosporine and methotrexate “head to head,” both drugs performed well. (Seventy-one percent of patients taking cyclosporine and 60% of patients taking methotrexate experienced at least a 75% improvement in PASI score; the difference was not statistically significant.)
While the figures vary in these different studies, it is pretty clear that methotrexate does not clear as many patients as thoroughly as the biologics, but it does help most patients somewhat. Also, it is important to note that methotrexate also improves symptoms of psoriatic arthritis, which is part of why (along with its low cost) it continues to be widely prescribed for psoriasis and psoriatic arthritis, alone or in combination with other treatments.
Methotrexate is effective, relatively inexpensive, and convenient to take. Unlike cyclosporine, methotrexate can be used for longer periods of time, as long as patients are monitored for liver damage and other potentially serious side effects. Methotrexate is also increasingly being used in combination with biologics like Humira (adalimumab), because of research suggesting it helps biologics work better and may reduce the risk of building up resistance to the biologic. (Of course, this is a bit ironic since biologics had been promoted, in part, as a way to reduce the use of methotrexate and its unwelcome side-effects.)
Methotrexate can cause serious liver damage. The damage is not always evident in blood tests for liver function, so liver biopsy, a procedure during which a small sample of liver tissue is collected and examined in a laboratory, is recommended after every 1 ½-2 years of methotrexate treatment. According to one study, 14% of patients who had been taking methotrexate for an average of 237 weeks had to stop because of liver problems. To lessen the risk, patients should not drink alcohol while taking methotrexate and those who already have liver disease should not use the drug. Folic acid supplements may help protect the liver. If patients follow the recommended monitoring scheme and stop using methotrexate at the first sign of liver problems, the damage is usually reversible.
Other serious potential side effects of methotrexate include a drop in white blood cell production, lung disease, and skin reactions, so patients should be carefully checked for these conditions during treatment.
The most common less serious side effect of methotrexate use is nausea. Taking supplemental folic acid or anti-nausea medications can help control this symptom.
Methotrexate causes birth defects and miscarriages, so women taking the drug must be careful to avoid conception. Further, it is advisable for women to wait six months after stopping methotrexate before trying to conceive. Men are also typically advised to stop using methotrexate and wait three-to-six months before trying to conceive, due to risk of temporary infertility and/or risk to the fetus/baby, but a study that reviewed available data found the risks largely theoretical, and men have fathered healthy children while taking methotrexate during conception.
How does it work?
At the high doses used to treat cancer, methotrexate blocks synthesis of DNA and RNA, thereby preventing tumor cells from dividing. Interestingly, methotrexate can control psoriasis at a 100-fold lower dosage, suggesting that it may be working by a different mechanism. According to one theory, methotrexate prevents immune cells from displaying certain molecules on their outer surfaces that are necessary for cell-to-cell communication and interaction. Without these molecules, the cells are unable to congregate in the skin or trigger the inflammatory reaction that leads to the formation of psoriasis plaques.