Leflunomide for Psoriasis and Psoriatic Arthritis

There are a variety of treatment options for people with moderate to severe psoriasis or psoriatic arthritis. One less commonly used agent is the drug leflunomide. It may make sense for you if your disease isn’t responding well, or if you are unable to take other treatments.

What Is Leflunomide?

Leflunomide (trade name Arava) is an oral drug that can be used to treat psoriatic arthritis and moderate to severe psoriasis.

The drug’s chemical name is N-(4´-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide.

The FDA originally approved leflunomide for the treatment of rheumatoid arthritis. Technically speaking, leflunomide has never been approved by the FDA to treat psoriasis and psoriatic arthritis—the necessary clinical trials have not been performed. However, both psoriasis and rheumatoid arthritis are autoimmune inflammatory conditions that can affect the joints, and they share some similar physiological processes. Some clinical studies suggest that leflunomide is effective in treating skin symptoms in psoriasis and both skin and joint symptoms in people with psoriatic arthritis. So physicians sometime prescribe the drug “off label.”

Leflunomide is one of the older traditional drugs that can be used to treat moderate to severe psoriasis and psoriatic arthritis. That puts it in a group with methotrexate, cyclosporine, and other drugs.

However, leflunomide is not used as commonly as these other drugs. You might hear these drugs called DMARDs or disease-modifying antirheumatic drugs. Like these drugs, leflunomide is not one of the newer “biologic” drugs that are made from human or animal proteins.

How Leflunomide Works

Leflunomide’s mechanism of action is not fully known.

However, it appears to work at least in part by inhibiting an enzyme needed to make new DNA (your inherited genetic material). When inflammation occurs, your body makes new inflammatory immune cells. By slowing down DNA synthesis, leflunomide may be able to block some of the inflammation that causes symptoms of psoriasis and psoriatic arthritis. However, because it suppresses the immune system, it can have other side effects.

Dosage and Administration

Take leflunomide by mouth with food, as prescribed by your doctor. The drug is available in 10mg, 20mg, and 100mg forms. When you initially start the drug, your doctor may give you a larger dose than normal, called a “loading dose” (typically 100mg for three days). After the drug level rises in your body, you will take a lower maintenance dose (typically 20mg daily).

Who It's For

There are a variety of other traditional oral drugs to treat psoriasis, like methotrexate. Other newer “biologic” drugs like Enbrel (etanercept) are also available. Doctors typically only prescribe leflunomide after other treatment options haven’t been successful. However, newer biologic drugs must be taken through a vein, and they are more expensive than non-biologic treatments.

If another oral drug hasn’t worked for you, you might want to try leflunomide before moving to a biologic drug. In some cases, your doctor might prescribe leflunomide in addition to another oral drug, like methotrexate.

People with mild psoriasis should use topical treatments and not oral drugs like leflunomide.

Possible Side Effects

Some of the most common side effects of leflunomide result from irritation of the gastrointestinal system. For example, these might include:

• Diarrhea (most common)
• Nausea
• Upset stomach

Other possible side effects include:

• Rash (rarely severe)
• Hair loss
• Elevated liver enzymes (indicating liver damage)

• Increased risk of infection
• Decreased blood cells or platelets (from decreased production in the bone marrow)

Other rare side effects are:

• Pulmonary fibrosis
• Pain with urination
• Neurological symptoms like disorientation or dizziness

Monitoring

Before starting leflunomide, your doctor will take your medical history and perform a physical exam. This helps your doctor make sure there isn’t a reason that leflunomide would be a bad choice for you. Make sure to tell your doctor about all the medications that you take, including over-the-counter medications. These might affect the effectiveness of leflunomide and its potential risks.

Because of the risk of certain drug side effects, people taking leflunomide need certain regular laboratory tests. You will need these before initially starting treatment and then at regular intervals. For example, you may need the following tests:

• Complete blood count (to monitor your red blood cells, white blood cells, and platelets)
• Liver tests, such as ALT

People taking leflunomide also need an initial screening test to make sure they don’t have a dormant case of tuberculosis. (Drugs like leflunomide might make the disease more active.)

Vaccines and Leflunomide

People taking leflunomide shouldn’t have certain types of vaccines that contain part of an alive virus. That doesn’t mean you shouldn’t take all vaccines—just ask your doctor first. You may want to get certain vaccines (such as a tetanus booster) before you start taking leflunomide.

Contraindications

You shouldn’t take leflunomide if you have a known allergy to the drug or one of its components. You also shouldn’t take leflunomide if your immune system is compromised by any of the following:

• A severe immunodeficiency disease
• Existing problems with your bone marrow
• An existing severe, uncontrolled infection

Pregnant women also should not take leflunomide.

Child-Bearing Potential

Leflunomide is a category X medication during pregnancy, which means that the known risks of the drug outweigh any potential benefits. It is thought to increase the risk of fetal death and birth defects. All women of childbearing potential need to have a pregnancy test before starting the drug. You should continue to use reliable contraception the entire time you take leflunomide.

If you are taking leflunomide and become pregnant, call your doctor’s office immediately and tell them your situation. Your doctor can advise you about potential risk to your pregnancy. Your doctor may be able to prescribe a drug washout treatment (called cholestyramine) that can rapidly lower the concentrations of leflunomide. This lowers the risk of harm to the fetus.

If you are taking and leflunomide and wish to become pregnant, talk to your doctor before starting to try to conceive. It is recommended that all women of childbearing age go through drug washout to rapidly lower concentrations of leflunomide. This is especially important for women actively trying to conceive. Without going through this step, it may take up to two years for leflunomide to fall to safe levels for a fetus in your body. Women should also not take leflunomide while breastfeeding.

Scientists believe that leflunomide probably doesn’t increase the risk of fetal birth defects for men fathering children. However, these animal studies have not been performed. To avoid any possible risk, men should stopping taking the drug before trying to conceive with their partner. Ideally they should go through the drug washout step as well.

A Word From Verywell

Fortunately, there are now a number of options for people with moderate to severe psoriasis or psoriatic arthritis. Leflunomide might be one option to consider if what you have tried hasn’t effectively controlled your disease.