woman taking her medication with a glass of water

Methotrexate: Can This Psoriasis Medication Improve Your Symptoms?

By Kerry Weiss
Reviewed by Allison Truong, M.D.
January 30, 2023

Dermatologists have been using methotrexate to treat psoriasis since the 1970s. And many people with the condition have questions about this popular psoriasis medication. How does it work? What are the side effects? How do I know if it’s right for me?

Here are the answers to some of the most frequently asked questions about treating psoriasis with methotrexate.

What Is Methotrexate?

Methotrexate is a medication that can be prescribed to treat moderate to severe cases of psoriasis. “It came into medicine to be used as a chemotherapeutic drug, but now it’s also used to treat chronic inflammatory diseases like psoriasis or psoriatic arthritis,” explains Anthony Fernandez, M.D., Ph.D., a dermatologist at the Cleveland Clinic in Ohio.

Methotrexate can be taken orally, either as a pill or liquid, or some people may be prescribed injectable methotrexate, says Saakshi Khattri, M.D., an assistant professor of dermatology at the Icahn School of Medicine at Mount Sinai Hospital in New York City. It’s often prescribed as a once weekly treatment, usually 15 to 25 milligrams. On days that person does not take methotrexate, they’re often asked to take folic acid to prevent side effects.

It’s important to discuss with your doctor what form might be best for you. Once you’ve gotten your prescription, be sure you understand exactly how—and how often—to take your medication, and ask your doctor or pharmacist if you have any questions about following your treatment regimen as directed.

How Does Methotrexate Work?

Psoriasis is thought to be caused by an overactive immune system that speeds up skin-cell growth, causing excess skin cells to pile up on the skin’s surface and create psoriasis plaques. Methotrexate works by suppressing the immune system as a whole to help gain control of that overactivity.

“By doing that, it helps to get rid of the skin rash associated with psoriasis, as well as the associated symptoms,” says Fernandez, which can include itching and burning.

Is Methotrexate Right for You?

Methotrexate isn’t typically prescribed for more mild cases of psoriasis that can be controlled with other, more conservative treatment options such as topical therapies.

“It’s usually reserved for patients who have moderate to severe psoriasis—so those who typically have at least 5 percent body-surface involvement,” explains Fernandez. “Methotrexate may also be prescribed for those who have psoriasis in sensitive locations, like the genitals, face, palms of the hands, or the soles of the feet, where it severely affects quality of life, regardless of the amount of body-surface area.”

Methotrexate can also be used to help treat psoriatic arthritis, a type of arthritis that affects approximately 30 percent of people with psoriasis. “Methotrexate may improve joint symptoms and help achieve minimal disease activity in psoriatic arthritis,” says Khattri.

It may also be prescribed in combination with other psoriasis treatments. “We often add on some amount of methotrexate for patients who are taking biologic medications and are looking for a little more clearance or a little more relief in their symptoms,” explains Fernandez. Biologic medications are injectable drugs that work to suppress specific parts of the immune system to calm inflammation and ease symptoms.

Sometimes, even people on systemic biologic therapies have stubborn plaques that won’t resolve or flares that come up, and methotrexate can calm these down. Alternatively, some people might find that their skin is improved with biologic therapy, but perhaps their arthritis is not. Adding on methotrexate in this case may calm down both the skin and joints.

Rarely, a person notices that the biologic they’ve been on for years is no longer helping their psoriasis. In this case, they may be developing antibodies against the biologic itself, making it less effective. Adding on methotrexate in this case may block the body’s ability to make anti-drug antibodies, getting the person back into remission.

Who Should Avoid Methotrexate?

Not everyone is a good candidate for methotrexate. The medication is associated with certain side effects that people with certain health conditions are at higher risk for. “When we think about some of the adverse events associated with methotrexate, we typically try to avoid giving it to certain patients,” says Fernandez. That includes people who:

  • Have chronic liver inflammation or disease
  • Drink a considerable amount of alcohol
  • Have severe kidney disease
  • Have significant anemia (or low red-blood-cell counts)
  • Have an immunodeficiency syndrome
  • Have active infectious disease (such as tuberculosis of hepatitis)
  • Have an active peptic ulcer
  • Take certain medications long-term (i.e., nonsteroidal anti-inflammatory drugs, NSAIDs)
  • Are trying to conceive or are pregnant or breastfeeding

“For these people, we try to use something else to treat their psoriasis,” explains Fernandez. Other treatments range from topicals to phototherapy to biologics.

What Are the Potential Side Effects?

There are quite a few potential side effects to look out for when taking methotrexate. “Gastrointestinal issues are really the main side effects,” says Khattri, though there are others to be on the lookout for, as well. The most common side effects are:

  • Vomiting
  • Nausea
  • Diarrhea
  • Loss of appetite
  • Mouth ulcers
  • Fatigue
  • Hair thinning/hair loss

Make sure you report any side effects to your dermatologist, who can help you find relief. For example, you may be able to ease gastrointestinal symptoms by adding more folic acid supplements to your treatment plan or by switching from an oral to an injectable methotrexate.

Less common, more serious side effects include anemia and inflammation of the liver. “Luckily, since methotrexate has been around for more than 50 years, this is well known, so we monitor regularly for these issues,” says Fernandez. “If we find that they’re occurring, we can adjust the dose of the medication, or, in significant cases, stop the medication, and things usually go back to baseline.” Common labs that are tested while on methotrexate include complete blood counts and complete metabolic panel including liver function tests. For patients that have been on methotrexate for many years, liver ultrasound or other liver-specific blood tests (i.e., amino terminal type III procollagen peptide P3NP) may be used to evaluate for signs of liver fibrosis.

What Types of Results Can Methotrexate Offer?

“In an ideal world, methotrexate helps clear your psoriasis,” says Fernandez. “What we’re looking for is significant improvement in the amount of active-psoriasis skin involvement, and a significant improvement in associated symptoms like skin pain and itching.”

According to the National Psoriasis Foundation, the goal for most people’s treatment should be to reduce psoriasis down to 1 percent or less of their body-surface area within three months. With methotrexate, most people will notice improvements to their psoriasis within four to six weeks of starting treatment.

“If you’re not getting a significant improvement in the amount of skin psoriasis and its symptoms after several months, work with your doctor,” says Fernandez. Depending on your individual case, your doctor may recommend making a treatment change, such as increasing the dose of methotrexate or switching to a new treatment altogether.

In fact, many doctors aren’t prescribing methotrexate as much as they used to, since biologics have come onto the scene in recent years. “We have such great biologics for psoriasis that methotrexate isn’t typically our go-to for psoriasis,” says Khattri. “Though it can be used in addition to a biologic, or in cases where insurance won’t cover a biologic, or the individual doesn’t want a biologic.”

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