Methotrexate is an immunosuppressant drug that helps reduce inflammation in the body. While it is generally an effective treatment for psoriatic arthritis, it can cause unwanted side effects.

Psoriatic arthritis (PsA) is an autoimmune condition that causes chronic inflammation of the skin, joints, and connective tissues. This typically causes symptoms such as pain, stiffness, and swelling.

According to an article in JAAD, it affects around 1 in 4 people with the skin condition psoriasis.

Methotrexate is a disease-modifying anti-rheumatic drug (DMARD). This class of drug affects immune system activity and can reduce inflammation, pain, and swelling in PsA.

This article describes how methotrexate works to treat PsA. It also looks at the potential side effects of methotrexate and outlines some alternative treatment options available.

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Methotrexate is an immunosuppressant drug, which means it suppresses the activity of the immune system. This helps to reduce inflammation and associated pain and swelling. It is a common first-line treatment for psoriatic arthritis treatment.

Methotrexate has several beneficial effects in the treatment of PsA, including:

  • Assisting tissue repair: Methotrexate helps white blood cells to repair damaged tissues.
  • Increasing adenosine production: According to the Arthritis Foundation, methotrexate causes cells to release adenosine, which is a molecule that blocks inflammation-promoting chemicals.
  • Slowing down the production of cytokines: Cytokines are proteins that promote inflammation. Typically, people with PsA have increased levels of cytokines within their joints. An older study from 2003 suggests that methotrexate helps to inhibit the production of cytokines.

Methotrexate can alleviate the symptoms of PsA while helping to prevent further joint damage.

There is some confusion as to the safety of methotrexate. This is because doctors sometimes prescribe very high doses of methotrexate to treat certain cancers.

The dosages required to treat PsA are much lower, with most people taking between 10 milligrams (mg) and 25 mg per week. Some people may also see improvement with dosages as low as 2.5 mg. These low doses are less likely to cause severe side effects.

In fact, according to the Arthritis Foundation, methotrexate is one of the safest arthritis drugs available.

It is essential to take methotrexate according to the doctor’s instructions. Taking too much methotrexate or taking the medication too often can be dangerous.

Methotrexate can cause side effects in some people. While serious side effects are less common, some of these effects can be life threatening.

The table below shows the most common side effects of methotrexate and their prevalence among people who take the drug for PsA.

Side effectSigns and symptomsPrevalence
Digestive problems nausea
stomach pain
appetite loss
up to 65% of users
Mouth ulcers or sores painful bumps or sores on the tongue, palate, gums, or inner cheeksup to 33% of users
Methotrexate “fog” (occurring a day or so after taking a dose of methotrexate)headaches
Hair loss thinning hair, or bald patchesbetween 1% and 3% of users

Methotrexate can also cause severe side effects, but these are much less common.

Use of the drug can potentially lead to inflammation and a buildup of scar tissue in areas such as the liver and lungs. It can also potentially cause drops in white blood cell levels and platelet production.

The table below lists severe side effects and their associated symptoms.

Side effectSymptoms
Blood disordervomiting blood
bleeding gums
blood in the urine
increased sensitivity to bruising
Infectionmuscle aches
sore throat
Kidney problemsurinating more or less often, or not at all
swollen hands or feet
Liver problemsyellow discoloration of the skin or the whites of the eyes
Lung inflammationdifficulty breathing
chest pains
persistent, dry cough
Stevens-Johnson syndromesevere blisters or rash around the mouth, eyes, or genitals
Lymphoma (cancers of the lymphatic system)chills, fever, loss of appetite, tiredness, unexplained weight loss

The Arthritis Foundation warns that prolonged use of methotrexate can cause liver damage. Although this risk is low, a doctor may recommend regular blood tests to monitor the health of the liver. Reducing or avoiding alcohol intake may help to protect the liver.

To reduce the risk of side effects, a person can try splitting their usual dose of methotrexate. This will mean taking half the dose in the morning and the other half 12 hours later. A person can also split their dose into three parts, and take them in the morning, afternoon, and evening.

Other ways to manage or reduce the side effects of methotrexate include:

  • Taking folic acid: A folic acid supplement may help reduce the risk of digestive problems and mouth ulcers by 79%. A person should ask their doctor for advice on the appropriate dose and when to take it. Some people may benefit from taking a daily supplement, while others may need a single weekly dose.
  • Taking an antinausea medication: If nausea is severe, a doctor may prescribe anti-nausea medication to settle the stomach.
  • Taking injectable methotrexate: People who experience nausea can also talk with a doctor about switching to injectable methotrexate. This treatment bypasses the stomach, so it may help prevent nausea.
  • Using an analgesic mouthwash: Some mouthwashes contain pain relievers such as lidocaine. These should help to alleviate pain from mouth ulcers and mouth sores.
  • Avoiding excess sun exposure: Methotrexate makes the skin more sensitive to sunlight. People can protect their skin by wearing high-SPF sunscreen and long-sleeved clothing. People should also avoid sun lamps and tanning beds.

Methotrexate is not suitable for the following people:

  • women who are pregnant or nursing
  • people who are allergic to methotrexate
  • People who experience severe side effects in response to taking methotrexate
  • people who take medications that may interact with methotrexate
  • people with chronic liver disease, alcohol-related liver disease, or alcohol use disorder
  • people who are immunocompromised
  • people with a pre-existing blood disorder, such as:

Other PsA treatments are available. As with methotrexate, these treatments aim to:

  • reduce pain and swelling
  • keep joints mobile
  • prevent further damage to the joints

We outline some alternative PsA below. In some cases, a doctor may recommend combining different treatments.

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often the first-line treatment for PsA. These drugs help to reduce inflammation and alleviate pain.

Examples include:

  • traditional NSAIDs, such as ibuprofen, naproxen, and diclofenac
  • COX-2 inhibitors, such as celecoxib and etoricoxib

It is important to note that using NSAIDs to treat PsA is an off-label use. This means the Food and Drug Administration (FDA) has not approved the drugs for treating PsA, but they may be useful.


Corticosteroids are a class of natural or synthetic hormones that help reduce inflammation in the body. Corticosteroids are available in both oral and injectable forms.

A doctor may use a corticosteroid injection to treat inflammation in a single joint. The results can last from a few weeks to several months.

Other DMARDs

Methotrexate is a disease-modifying anti-rheumatic drug (DMARD). These drugs block inflammatory processes in the body, helping slow the progression of PsA.

Besides methotrexate, other DMARDs include leflunomide and sulfasalazine. Doctors may prescribe either medication as an alternative to methotrexate. Taking DMARDs to treat PsA is also an off-label use.

DMARDs can take several weeks or months to have a noticeable effect.

Biological treatments

Biological treatments or “biologics” are a newer class of drugs that a doctor may prescribe to treat PsA. The National Psoriasis Foundation explains that these treatments block the action of specific immune cells or proteins that trigger inflammation in the lining of the joints.

Some examples of biologics include:

  • tumor necrosis factor-alpha inhibitors
  • interleukin 12 and 23 (IL-12/23) inhibitors
  • interleukin 17 (IL-17) inhibitors
  • interleukin 23 (IL-23) inhibitors
  • T cell inhibitors

A doctor will administer biologics via injection into a vein. Doctors usually recommend an initial 3-month course of biologic treatment. If effective, a person can continue the treatment for longer. If it is ineffective, a doctor may recommend switching to a different biologic.

Biologics can increase the risk of infection. As such, they are not suitable for people who have a compromised immune system.

Below are common questions relating to PsA and methotrexate.

How long does it take for methotrexate to help psoriatic arthritis?

Methotrexate can reduce psoriasis symptoms within 4–6 weeks. The drug may start to reduce arthritis inflammation and pain within 6–8 weeks, but it may take up to 6 months for people to experience its full effect.

How effective is methotrexate for psoriatic arthritis?

Methotrexate is often an effective treatment for PsA, but it may not work for everyone. A 2022 review concluded that targeted therapies are a more effective first-line treatment for PsA than methotrexate.

What is the safest drug for psoriatic arthritis?

Every person is different, and some people may tolerate specific treatments better than others. As a result, the safest and most effective PsA treatment can vary between cases. However, many NSAIDs, DMARDs, corticosteroids, and biologics are safe for treating PsA and have full approval from the FDA.

Methotrexate is an immunosuppressant drug. It helps alleviate the symptoms of PsA and slow the progression of the disease.

Methotrexate is generally safe when people take it at doses to treat PsA. Nonetheless, some people may experience side effects, such as digestive issues, mouth sores, and methotrexate fog.

People who experience side effects can try splitting their methotrexate dose over a 12-hour period.

Methotrexate is not suitable for everyone. Other treatment options for PsA include NSAIDs, corticosteroids, and biologics. Individuals should talk with their doctors about their treatment options.