What You Should Know About Methotrexate for Psoriatic Arthritis

Psoriatic arthritis is an autoimmune condition that involves both psoriasis and inflammatory arthritis. It can cause joint pain, inflammation, and skin problems.

Psoriatic arthritis can lead to joint damage over time. Thankfully, immunosuppressant medications can help reduce symptoms and slow down the damage caused by this condition. Methotrexate (Trexall) is a common first-choice option. But how does it work? And how effective is it? 

Here, we’ll cover everything you need to know about methotrexate for psoriatic arthritis.

What is methotrexate?

Methotrexate is part of a medication class known as disease-modifying antirheumatic drugs (DMARDs). DMARDs are used to treat many autoimmune conditions, such as rheumatoid arthritis, lupus, and more.

At high doses, methotrexate is FDA approved as chemotherapy to treat some cancers. At low doses, methotrexate can treat a variety of autoimmune conditions, such as rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriasis. At low doses, methotrexate is not considered chemotherapy.

How does methotrexate work for psoriatic arthritis?

Methotrexate isn’t approved for psoriatic arthritis specifically, but it’s often prescribed off-label for this condition. It works by reducing inflammation in the body.

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Methotrexate reduces inflammation in a couple of different ways. It increases the levels of a chemical called adenosine, which in turn reduces the activity of T- and B-cells (cells involved in immune system activity). Methotrexate also blocks the activity of interleukin-1B, an immune system protein.

Methotrexate improves psoriatic arthritis symptoms, including psoriasis rashes, joint swelling, and joint pain.

How effective is methotrexate for psoriatic arthritis?

In recent years, the effectiveness of methotrexate for psoriatic arthritis has come into question. For severe psoriasis symptoms, a biologic medication is likely to provide better results.

But methotrexate is still an effective first-choice option for those who:

• Have milder psoriatic arthritis symptoms

• Prefer oral pills (most biologics are injections)

• Are at high risk or have a history of serious infections

• Have a history of cancer

• Don’t have access to biologic medications (Methotrexate is a much more affordable option)

What is the typical methotrexate dosage for psoriatic arthritis?

Methotrexate comes as an injection or oral tablet. For psoriatic arthritis, methotrexate is typically prescribed as oral tablets you’ll take as a single dose once per week. But since it isn’t FDA approved for this condition, there also isn’t an approved dosage that’s recommended.

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According to Dr. Samantha Shapiro, a board-certified rheumatologist and internist, the usual dose is somewhere between 7.5 mg to 25 mg per week. 

“However, most rheumatologists will attest that 15 mg is typically the minimum effective dose,” Shapiro said. And most clinical studies on methotrexate for psoriatic arthritis also used 15 mg once weekly.

Methotrexate only comes in 2.5 mg tablets. So in most cases you’ll need to take several tablets at once to reach the appropriate dosage. Your prescriber may increase your dosage if you need more symptom relief. Or lower it if you experience bothersome side effects.

Methotrexate lowers folic acid levels while you’re taking it. So you’ll also take folic acid along with it to keep your levels up and reduce side effects. The recommended folic acid dosage with methotrexate is typically either 1 mg daily or 5 mg once a week. Your prescriber will give you instructions based on your specific needs.

What are the side effects of methotrexate?

Like any medication, methotrexate can cause side effects. Below are common and rare methotrexate side effects to be aware of.

Common side effects

Some common side effects of methotrexate for psoriatic arthritis include:

• Headache

• Nausea and vomiting

• Diarrhea

• Increased skin sensitivity to the sun (photosensitivity)

• Mild liver problems

• Mouth sores

Of note, stomach-related symptoms (nausea, vomiting, diarrhea) often go away as your body gets used to the medication.

Serious side effects

It’s important to see your prescriber regularly while taking methotrexate. This helps them keep an eye out for serious side effects, such as:

• Severely low blood cell counts

• Serious liver damage

• Kidney problems

• Lung inflammation 

• Serious skin conditions, including Stevens-Johnson syndrome

Some of these side effects are less likely with the low methotrexate doses used for psoriatic arthritis. It’s best to avoid drinking alcohol while taking methotrexate. Alcohol increases the chances of liver damage while taking this medication.

For more information on serious side effects, check out our in-depth article on methotrexate toxicity.

What are some alternatives to methotrexate for psoriatic arthritis?

Your psoriatic arthritis treatment plan will depend on both your symptoms and their severity. Your other health conditions and medical history also play a role.

Methotrexate alternatives for psoriatic arthritis treatment include:

• Leflunomide (Arava)

• Cyclosporine (Gengraf)

• Tumor necrosis factor (TNF) alpha inhibitors, such as Enbrel (etanercept) and Humira (adalimumab)

• Interleukin inhibitors, such as Cosentyx (secukinumab) and Stelara (ustekinumab)

• T-cell inhibitors, such as Orencia (abatacept)

• Janus kinase (JAK) inhibitors, such as Xeljanz (tofacitinib) and Rinvoq (upadacitinib)

• Phosphodiesterase-4 (PDE4) inhibitors, such as Otezla (apremilast)

Who shouldn’t use methotrexate for psoriatic arthritis?

You shouldn’t take methotrexate if you:

• Are pregnant or considering becoming pregnant

• Have an allergy to methotrexate

• Are living with a chronic liver disease, including damage caused by heavy alcohol use (alcoholic hepatitis) or scarring of the liver (cirrhosis)

• Are living with kidney disease

Your healthcare team will review your medical history before prescribing methotrexate to ensure it’s a safe option for you. Be sure they’re aware of any past or present conditions as well as other medications you’re taking.

How to save on the cost of methotrexate

Oral methotrexate tablets are available as both a brand-name medication as well as a lower-cost generic. And generic methotrexate tablets are generally much more affordable than other psoriatic arthritis medications.

GoodRx can help you save over 80% off the average retail price of generic methotrexate tablets. The price of methotrexate tablets at certain pharmacies is as low as $12.17 with a free GoodRx discount.

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Written by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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