Methotrexate Treatment for Psoriatic Arthritis

Methotrexate remains a drug of choice for psoriatic arthritis, despite research that questions its disease-modifying effects.


Originally developed as a cancer treatment, methotrexate has become one of the most prescribed medications for inflammatory arthritis. For psoriatic arthritis (PsA), methotrexate is the drug of choice because in the clinical setting it appears to work well on both the joint and skin manifestations. Although the exact mechanism of methotrexate in psoriatic arthritis is not known, it is believed to interfere with skin cell proliferation that causes the scaly build up and suppresses the overactive immune response that causes joint inflammation and damage.

Methotrexate is FDA approved for the skin condition psoriasis, but it is frequently used off-label for psoriatic arthritis. The drug can be taken by mouth or injection. For active psoriasis, the typical dose is 10 to 25 mg per week, not to exceed 30 mg per week. For psoriatic arthritis, the dose is typically 7.5 mg to 20 mg per week.

Does Methotrexate Slow Psoriatic Arthritis Activity?

Despite its wide use in PsA, there is little scientific evidence to support the use of methotrexate as a disease-modifying agent for psoriatic arthritis.

In fact, in the first large, double-blind, placebo-controlled study of methotrexate for psoriatic arthritis, published in 2012 in the journal Rheumatology, British researchers found methotrexate had no significant effect on objective measures of disease activity. In a separate study, published in 2014 in Annals of the Rheumatic Diseases, Canadian researchers found that that methotrexate was less effective than tumor necrosis factor-blocking agents in inhibiting the progression of radiographic joint damage in people with psoriatic arthritis.

But these findings have not caused doctors to shun methotrexate in psoriatic arthritis treatment. In the British study, methotrexate did seem to offer subjective benefits for some – that is, doctors and patients agreed the drug was beneficial based on the doctors’ observations and the patients’ reports on how they felt – which doctors say is not an unimportant consideration.

Doctors Find Benefit of Methotrexate in PsA

“Do many patients on methotrexate feel better? My perception is they do,” says Bernard Rubin, DO, division head for rheumatology at the Henry Ford Hospital in Detroit, who was not involved in the study. “There are a lot of measures of patient global well-being. If the patient feels better, that is one of your outcomes,” he says.

Furthermore, the trial included 221 patients with all types of psoriatic arthritis – a disease that is highly variable. Some patients tend to do better with methotrexate than others, says Dr. Rubin, noting that he has found methotrexate does provide symptomatic relief to some of his patients with multiple joint involvement and psoriasis.

Eric Matteson, MD, chair of rheumatology at the Mayo Clinic in Rochester, Minn, says he has had similar experiences. “In my view and experience, methotrexate does work for individual patients with peripheral joint disease, especially in the hands and feet,” he says.

Bottom Line

Studies may show that methotrexate does not consistently slow PsA activity, but many doctors have found great benefit for their patients. If your doctor prescribes methotrexate, it is important to be monitored regularly, both for the effectiveness of the drug on your psoriatic arthritis and also for potential adverse effects on the blood cells and liver. Many side effects of methotrexate can be avoided or resolved by taking a folic acid supplement or adjusting the medication dosage. If methotrexate alone does not control your psoriatic arthritis, your doctor may add a biologic agent to your treatment plan.

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