Methotrexate is a common treatment option for psoriasis. Newer medications are more effective, so methotrexate may be prescribed if other medications have not helped.

Methotrexate (MTX) is a drug that has been used to treat psoriatic arthritis (PsA) for more than 40 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 to manage PsA.

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

  • costs less than alternatives
  • helps reduce inflammation
  • improves skin symptoms

When used by itself, MTX cannot prevent joint damage. Discuss with your doctor whether MTX alone or in combination with other drugs might be a good treatment option for you.

MTX is an antimetabolite drug, which means that it interferes with the typical 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 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 Food and Drug Administration (FDA) in 1972 for severe psoriasis (which is often related to psoriatic arthritis), but it’s also been widely used “off-label” for PsA. “Off-label” means doctors can prescribe it beyond its original use.

The Joint American Academy of Dermatology AAD and National Psoriasis Foundation (NPF) recommends MTX as a treatment for adult psoriasis. However, more effective medications like adalimumab and infliximab often serve as first-line options due to their greater effectiveness.

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

A clinical trial published in 2018 found that 22% 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 begin your treatment with MTX. It’s less expensive than the biologic drugs developed in the early 2000s. However, medications like adalimumab and infliximab are more effective than MTX.

MTX doesn’t prevent joint damage in PsA. So, if you’re at risk for bone damage, your doctor may add in one of the biologics. These drugs inhibit the 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 to fetal development. If you’re trying to get pregnant, or if you’re pregnant, avoid MTX. It is not safe for use during pregnancy.

Liver damage

About 1 in 200 people taking MTX experience liver damage. But the damage is reversible when when you stop MTX. Research suggests 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
  • have obesity
  • have diabetes
  • have reduced 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 MTX’s side effects. Some antibiotics may also interact to reduce MTX’s effectiveness or may be harmful. Talk with your doctor about your medications and and how they might interact with MTX.

The typical 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, either orally of through injection. The oral form of MTX may be in pill or liquid form. Some people may choose to break up the dose into three parts on the day they take it to help manage potential 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 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

Newer treatments are available, but they usually cost more. Research into new treatments is ongoing, and other new treatments may be available in the future.

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

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 that targets interleukin-12 and interleukin-23
  • secukinumab (Cosentyx), which targets interleukin-17A

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

All 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 eases symptoms. However, it can also have serious side effects, so you’ll need regular checkups.

If PsA affects many joints, your doctor might suggest combining MTX with a biologic DMARD to stop joint damage. Talk with your doctor about your treatment options and review your treatment plan regularly. New treatments may become available as research continues.

You may also find it useful to talk with a “patient navigator” at the National Psoriasis Foundation.