Methotrexate (MTX) is a drug that’s been used to treat psoriatic arthritis for more than 50 years. Alone or in combination with other therapies, MTX is considered a first-line treatment for moderate to severe psoriatic arthritis (PsA). Today, it’s usually used in combination with new biologic drugs for PsA.

MTX has potentially serious side effects. On the plus side, MTX:

  • is inexpensive
  • helps reduce inflammation
  • clears skin symptoms

But MTX doesn’t prevent joint destruction when used alone.

Discuss with your doctor whether MTX alone or in combination with other drugs might be a good treatment for you.

MTX is an antimetabolite drug, which means that it interferes with the normal functioning of cells, stopping them from dividing. It’s called a disease-modifying antirheumatic drug (DMARD) because it reduces joint inflammation.

Its initial use, dating back to the late 1940s, was in high doses to treat childhood leukemia. In low doses, MTX suppresses the immune system and inhibits the production of lymphoid tissue involved in PsA.

MTX was approved by the U.S. Food and Drug Administration (FDA) in 1972 for use with severe psoriasis (which is often related to psoriatic arthritis), but it’s also been widely used “off label” for PsA. “Off label” means your doctor can prescribe it for diseases other than the FDA-approved one.

The effectiveness of MTX for PsA hasn’t been studied in large-scale clinical trials, according to the American Academy of Dermatology (AAD). Instead, the AAD recommendations for MTX are based on the long-time experience and results of doctors who prescribed it for PsA.

A 2016 review article points out that no randomized control study demonstrated MTX joint improvement over that of a placebo. A six-month 2012 controlled trial of 221 people over six months found no evidence that MTX treatment alone improved joint swelling (synovitis) in PsA.

But there’s an important additional result. The 2012 study found that the MTX treatment did significantly improve the overall assessment of symptoms by both doctors and people with PsA involved in the study. Also, skin symptoms were improved with MTX.

Another study, reported in 2008, found that if people with PsA were treated early in the disease at an increased dose of MTX, they had better outcomes. Of the 59 people in the study:

  • 68 percent had a 40 percent decrease in actively inflamed joint count
  • 66 percent had a 40 percent decrease in swollen joint count
  • 57 percent had an improved Psoriasis Area and Severity Index (PASI)

This 2008 research was done at a Toronto clinic where a previous study had found no advantage for MTX treatment for joint swelling.

MTX works as an anti-inflammatory and can be useful on its own for mild cases of PsA.

A 2015 study found that 22 percent of people with PsA treated only with MTX achieved minimal disease activity.

MTX is effective in clearing skin involvement. For this reason, your doctor may start off your treatment with MTX. It’s less expensive than the newer biologic drugs developed in the early 2000s.

But MTX doesn’t prevent joint destruction in PsA. So if you’re at risk for bone destruction, your doctor may add in one of the biologics. These drugs inhibit production of tumor necrosis factor (TNF), an inflammation-causing substance in the blood.

The side effects of MTX use for people with PsA can be significant. It’s thought that genetics may play a role in individual reactions to MTX.

Fetal development

MTX is known to be harmful for fetal development. If you’re trying to get pregnant, or if you’re pregnant, stay off MTX.

Liver damage

The main risk is liver damage. About 1 in 200 people taking MTX have liver damage. But the damage is reversible when you stop MTX. According to the National Psoriasis Foundation, the risk starts after you reach a lifetime accumulation of 1.5 grams of MTX.

Your doctor will monitor your liver function while you’re taking MTX.

The risk of liver damage increases if you:

  • drink alcohol
  • are obese
  • have diabetes
  • have abnormal kidney function

Other side effects

Other potential side effects aren’t as serious, just uncomfortable and usually manageable. These include:

  • nausea or vomiting
  • fatigue
  • mouth sores
  • diarrhea
  • hair loss
  • dizziness
  • headache
  • chills
  • increased risk of infection
  • sensitivity to sunlight
  • burning feeling in skin lesions

Drug interactions

Some over-the-counter pain drugs such as aspirin (Bufferin) or ibuprofen (Advil) may increase side effects of MTX. Certain antibiotics may interact to reduce MTX effectiveness or may be harmful. Talk to your doctor about your medications and possible interactions with MTX.

The recommended starting dose of MTX for PsA is 5 to 10 milligrams (mg) per week for the first week or two. Depending on your response, the doctor will gradually increase the dose to reach 15 to 25 mg per week, which is considered the standard treatment.

MTX is taken once a week, by mouth or by injection. The oral MTX may be in pill or liquid form. Some people may break up the dose into three parts on the day they take it to help with side effects.

Your doctor may also prescribe a folic acid supplement, because MTX is known to reduce essential folate levels.

There are alternative drug treatments for PsA for people who can’t or don’t want to take MTX.

If you have very mild PsA, you may be able to relieve symptoms with nonsteroidal anti-inflammatory drugs (NSAIDs) alone. But NSAIDS aren’t effective with skin lesions. The same is true for local injections of corticosteroids, which may help with some symptoms.

Other conventional DMARDs

Conventional DMARDs in the same group as MTX are:

  • sulfasalazine (Azulfidine), which has been shown to improve arthritic symptoms but doesn’t stop joint damage
  • leflunomide (Arava), which has been shown to improve both joint and skin symptoms
  • cyclosporine (Neoral) and tacrolimus (Prograf), which work by inhibiting calcineurin and T-lymphocyte activity

These DMARDS are sometimes used in combination with other drugs.

Biologics

Many newer drugs are available, but these are more expensive. Research is ongoing, and it’s likely that other new treatments may be available in the future.

Biologics that inhibit TNF and decrease joint damage in PsA include these TNF alpha-blockers:

  • etanercept (Enbrel)
  • adalimumab (Humira)
  • infliximab (Remicade)

Biologics that target interleukin proteins (cytokines) can reduce inflammation and improve other symptoms. These are FDA-approved for treating PsA. They include:

  • ustekinumab (Stelara), a monoclonal antibody which targets interleukin-12 and interleukin-23
  • secukinamab (Cosentyx), which targets interleukin-17A

Another treatment option is the drug apremilast (Otezla), which targets molecules inside immune cells that are involved with inflammation. It stops the enzyme phosphodiesterase 4, or PDE4. Apremilast reduces inflammation and joint swelling.

All of the medications that treat PsA have side effects, so it’s important to evaluate the benefits and side effects with your doctor.

MTX can be a useful treatment for PsA because it reduces inflammation and helps symptoms overall. It also can have serious side effects, so you’ll need to be monitored regularly.

If more than one of your joints is involved, combining MTX with a biologic DMARD may be useful in stopping joint destruction. Discuss all the treatment options with your doctor, and review the treatment plan regularly. It’s likely that ongoing research into PsA remedies will come up with new drug therapies in the future.

You may also find it useful to talk with a “patient navigator” at the National Psoriasis Foundation, or join one of its psoriasis discussion groups.