Medically reviewed by William Truswell, MD
Methotrexate is a mainstay treatment for many autoimmune diseases, including psoriasis. It is known as a disease-modifying antirheumatic drug (DMARD) that slows down the effects of the immune system and disease progression over time.
The Food and Drug Administration (FDA) approved methotrexate for treating severe psoriasis in the 1970s. It is typically prescribed to people with psoriasis whose symptoms are debilitating or haven't responded to other treatments.
It is often prescribed for short periods for treating psoriasis. This is because of the increased risk for severe side effects, including liver and kidney problems. The aim of treating psoriasis with methotrexate is to reduce disease and symptom severity. Once symptoms improve, your healthcare provider will put you back on milder treatments.
This article will cover methotrexate and psoriasis, side effects of methotrexate, dosing and treatment length for psoriasis, results, monitoring, and more.
Methotrexate, Psoriasis, and Autoimmune Disease
Psoriasis is an autoimmune skin disease in which the immune system malfunctions and causes skin cells to grow much quicker than average. The skin cell overgrowth causes thick, scaly patches of skin to pile up on the skin's surface.
Methotrexate works by binding and inhibiting the inflammatory cells and processes involved in the rapid growth of skin cells and works to halt their growth rate. Methotrexate can be prescribed if your psoriasis is severe or your disease has not responded to other treatments.
Psoriasis can sometimes be challenging to treat. Fortunately, you have plenty of treatment options for the condition.
Psoriasis is not the only inflammatory disease that methotrexate can treat. For example, it is used to treat rheumatoid arthritis (RA) for longer periods than those recommended for psoriasis.
RA is a chronic inflammatory disease that causes chronic inflammation of the synovial linings of joints. It can also affect other body systems, including the skin, heart, lungs, eyes, and blood vessels.
Methotrexate is one of the first DMARDs recommended for treating RA, and it is typically combined with biologic DMARDs for managing the disease.
Additional conditions treated with methotrexate include:
Psoriatic arthritis (PsA)
Multiple sclerosis (MS)
Polyarticular juvenile idiopathic arthritis (polyarticular JIA)
Some types of cancers
Certain types of lymphoma
When treating autoimmune diseases like RA, PsA, Crohn's, MS, and polyarticular JIA, methotrexate decreases the effects of a malfunctioning immune system, including chronic inflammation. For treating cancer, the drug might slow down the growth of cancer cells.
Methotrexate Side Effects to Know Before Starting Treatment
Your risk for methotrexate liver damage increases if you regularly consume alcohol or have kidney or liver problems, obesity, or diabetes. The risk for certain cancers and bone marrow toxicity increases with long-term use of methotrexate. The drug can also decrease white blood cells, increasing the risk of severe infections.
Common side effects of methotrexate that often improve over time include:
Temporary hair loss
Serious side effects that should be reported to your healthcare provider include:
Signs of anemia (paleness, fatigue, etc.)
Signs of liver trouble (yellow eyes or skin, dark urine, stomach or abdominal pain, etc.)
Easy bleeding or bruising
Signs of kidney problems (i.e., change in urine output)
Dry cough or a cough that produces mucus
Get emergency medical help for these severe side effects:
Weakness on one side of the body
Mental health changes
Who Shouldn't Take Methotrexate for Psoriasis?
Most adults and children can take methotrexate to treat psoriasis. Even so, this drug may not be suitable for everyone.
If you have psoriasis, the following may exclude you from taking methotrexate or delay starting the drug:
Having an allergic reaction to methotrexate or any of its ingredients
Being pregnant, trying to get pregnant, or breastfeeding
A liver or kidney problem
A mouth ulcer, stomach ulcer, or duodenal ulcer
An upcoming surgery, including dental surgery
Unnecessary or prolonged sunlight or ultraviolet (UV) light exposure, tanning beds, and sunlamps
Certain medicines, including antibiotics and other DMARDs
You should inform your healthcare provider about all prescription and nonprescription medicines, including vitamins, supplements, and herbs you take. Some of these could interact with methotrexate and cause adverse reactions.
Starting Dose of Methotrexate for Psoriasis
Methotrexate is typically given once a week as an oral tablet or an injection. A typical starting dose is 5 to 25 milligrams (mg) weekly, commonly 7.5 mg or 15 mg. Your healthcare provider will keep you on the starting dose until they notice it is working.
Once the drug starts working, your healthcare provider will reduce the dosing to the lowest possible. They might increase the dose if they believe it might help you further.
When prescribed as an injection, methotrexate can be significantly more effective than oral methotrexate.
One 2019 meta-analysis of oral vs. injectable methotrexate for treating RA found that injection type offered significantly higher odds of reducing disease activity than oral methotrexate. The report's authors concluded that widespread use of injectable methotrexate could lead to better disease control and decreased need for biologic drug therapy.
Length of Prescription
If your healthcare provider prescribes methotrexate, they will prescribe it for the shortest time possible. This time could be six months, one year, and, in rare cases, up to two years.
You and your healthcare provider can determine how long treatment is necessary to get psoriasis under control. Once symptoms improve, you can return to milder treatments.
Methotrexate has been given for longer periods to slow disease progression in RA. For example, there have been studies on the long-term use of methotrexate for treating RA, some lasting a decade or longer, according to a 2013 Transactions of the American Clinical and Climatological Association report.
That report also noted concerns about the hepatotoxicity with methotrexate based on the psoriasis experience. Regarding methotrexate for treating RA, the report's authors noted the drug was well-tolerated despite concerns about gastrointestinal toxicity. Bone marrow, lung, and liver toxicity appeared to be rarer adverse effects of methotrexate.
Methotrexate is not your only option for managing psoriasis. Additional options for getting your psoriasis under control include:
Other DMARDs, such as Neoral (cyclosporine), Plaquenil (hydroxychloroquine), and Arava (leflunomide)
Biologic drug therapies, including Cimzia (certolizumab)
Light therapy (also called phototherapy)
Natural remedies to treat sore, inflamed skin, such as oatmeal and Epsom salt baths and moisturizers
Work with a dermatologist to develop a treatment plan based on your psoriasis type and specific symptoms. A dermatologist is a doctor who specializes in diagnosing and treating nail, skin, scalp, and hair conditions like psoriasis.
Results After Methotrexate Psoriasis Treatment
Unlike topical therapies, which work directly on skin lesions, methotrexate suppresses immune system processes that cause psoriasis skin lesions. It can start working as early as three weeks and may improve skin symptoms for as long as you use it.
It may take several months for some people to see any symptom improvement. Continue to take your medication exactly as prescribed, even if you do not see improvement immediately. This is the only way to reduce skin inflammation and symptoms associated with psoriasis.
Your healthcare provider can stop methotrexate once psoriasis is under control. Symptoms can return when you are no longer on the drug, but this does not mean symptoms have worsened because you stopped taking it.
Psoriasis is characterized by flare-ups (times when symptoms are worse), which are often the result of triggers, and remission (when the disease is under control). If your skin flares up again, your healthcare provider may put you back on methotrexate. You can come off it again once your skin is cleared.
Monitoring and Provider Check-ins on Methotrexate
Methotrexate is broken down in the liver and removed from the body with the assistance of the kidneys. As a result, it might cause harmful effects on these organs when used for long periods.
If you take the drug regularly, your healthcare provider will order routine blood work (three to four times a year) to confirm methotrexate is not affecting your liver or kidneys. Liver and kidney hypertoxicity are considered less common side effects of the drug.
The American College of Rheumatology (ACR) recommends monitoring liver enzymes (alanine transaminase and aspartate transaminase) and serum albumin (a protein made by the liver) at frequent intervals. Blood work will be done more often when you start treatment and can taper off to every three to four months after you have been on the drug for at least six months.
Elevations in liver enzymes and serum albumin markers might occur in the first few weeks of starting methotrexate, but this is not a reason to stop taking the medicine. Levels will improve as the body gets used to the drug. Your healthcare provider will continue to pay attention to liver enzyme abnormalities for as long as you are treated with methotrexate. If levels are high, your dosing will be adjusted.
Your healthcare provider may request imaging to look for liver damage if levels stay high despite a lower dose or discontinuing the drug. Rest assured, cases of severe liver damage are rare; most people can take methotrexate for years without problems.
Self-Care During Methotrexate Psoriasis Treatment
Methotrexate makes it more likely for you to get a sunburn. If you burn easily or have psoriasis-inflamed skin, a sunburn might be much worse for you, and cause you to experience further skin inflammation, redness, and peeling.
You will want to be careful while in the sun while on methotrexate. You may even want to limit your time in the sun to five minutes at a time. Protect your skin by wearing sunscreen that ha a sun protection factor (SPF) of at least 30. Avoid the sun when it is the warmest outside—usually between 10 a.m. and 2 p.m. You will also want to avoid tanning beds.
People with psoriasis have an increased risk for non-melanoma skin cancer even when not treated with methotrexate. Get ahead of any problems by seeing a dermatologist to manage psoriasis and for yearly skin checks.
How to Lower Medication Risks
Some people may need to stop taking methotrexate due to side effects. Common side effects that may lead to medication discontinuance are severe nausea, vomiting, diarrhea, thinning hair, mouth sores, and severe fatigue. Some side effects can be lessened by taking daily folic acid.
Your healthcare provider can best advise you on whether folic acid can help you and how much you can take. Folic acid amounts in most multivitamins are insufficient to counter methotrexate side effects. Additionally, folic acid may reduce the effectiveness of methotrexate. Your healthcare provider will only add it if the side effects of methotrexate are severe.
If folic acid does not help you, your healthcare provider can prescribe folinic acid, which is a different form of the vitamin available with a prescription.
Methotrexate is a commonly prescribed disease-modifying antirheumatic drug used to treat many autoimmune diseases, including psoriasis. It works by slowing down the effects of the immune system to inhibit the processes involved in the rapid growth of skin cells.
This drug is typically prescribed to people with severe psoriasis who have not responded to other treatments. It is given for short periods to treat psoriasis but can be used for extended periods for other inflammatory conditions like rheumatoid arthritis. Methotrexate for psoriasis is usually stopped once the disease is under control and skin symptoms have cleared.
A significant concern about treating psoriasis with methotrexate is the risk of liver damage. Even so, researchers have found such effects appeared to be rarer adverse effects of methotrexate. Common side effects of the drug are nausea, vomiting, stomach pain, dizziness, temporary hair loss, and fatigue. Many of these side effects improve over time or can be reduced by adding daily folic acid.
If a healthcare provider prescribes methotrexate for treating psoriasis, they will prescribe the smallest dose over the shortest time, which could be six months or up to two years. Methotrexate has been prescribed for more extended periods to treat RA, and researchers have found the drug is well-tolerated despite some safety concerns.
If you take methotrexate regularly, your healthcare provider will request blood work to monitor liver enzymes and proteins. If levels are high, your provider may discontinue treatment or reduce your dosing.
Your healthcare provider will determine methotrexate's effect in managing your psoriasis, can offer additional treatments, and advise you on side effects.
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