Leflunomide is a prescription medication used to treat active rheumatoid arthritis in adults. It works by suppressing the overactive immune response that drives joint inflammation, slowing disease progression and reducing pain, swelling, and stiffness. Sold under the brand name Arava, it belongs to a class of drugs called disease-modifying antirheumatic drugs (DMARDs).
How Leflunomide Works
In rheumatoid arthritis, certain immune cells called T-cells multiply aggressively and attack the lining of your joints. Leflunomide blocks an enzyme these cells need to reproduce. Without that enzyme, the T-cells stall in their growth cycle and can’t keep fueling inflammation. This is different from painkillers, which only mask symptoms. Leflunomide targets the underlying immune dysfunction, which is why it can slow or prevent the joint damage that worsens over time if rheumatoid arthritis goes untreated.
What It Treats Beyond Rheumatoid Arthritis
The only FDA-approved use for leflunomide is active rheumatoid arthritis in adults. However, doctors sometimes prescribe it off-label for related autoimmune conditions. Joint symptoms in lupus are the most studied of these off-label uses. In a review of lupus patients treated with leflunomide, nearly half achieved joint remission, with significant improvement in disease activity scores and inflammatory markers. It has also been used in psoriatic arthritis and, less commonly, in organ transplant patients dealing with certain viral infections.
How It’s Taken
Treatment typically starts with a higher loading dose of 100 mg once daily for three days, designed to build up drug levels in the body quickly. After that, the standard maintenance dose drops to 20 mg once daily. If that causes too many side effects, the dose can be reduced to 10 mg daily. Doses above 20 mg per day are not recommended.
Leflunomide is not a fast-acting drug. Most people begin to notice improvement in their symptoms after four to six weeks. The full benefit can take four to six months to develop, so sticking with the medication through that early period is important even if results feel slow at first.
Common Side Effects
Diarrhea is the most frequently reported side effect, affecting roughly 17% to 27% of patients in clinical trials, compared to about 12% of those taking a placebo. It tends to be most common in the early weeks and often improves over time.
Hair thinning occurs in about 10% to 17% of patients. This is usually mild and reversible, not the complete hair loss associated with chemotherapy. Elevated blood pressure is another common effect, showing up in about 10% of patients, roughly double the rate seen with placebo. If you already have high blood pressure, your doctor will likely want to monitor it more closely after starting the medication.
Liver Monitoring and Blood Tests
Leflunomide can stress the liver, so regular blood work is a non-negotiable part of treatment. Before starting the drug, you’ll have baseline liver enzyme levels checked, along with a complete blood count and blood pressure reading. These liver tests continue at regular intervals throughout treatment. If your liver enzymes are already more than twice the normal upper limit, leflunomide is not an option. The same applies to anyone with severe liver disease.
Screening for tuberculosis, both active and latent, is also part of the workup before starting treatment. Because leflunomide suppresses part of the immune system, it’s not recommended for people with severe immunodeficiency, bone marrow problems, or serious uncontrolled infections.
Pregnancy and Fertility Concerns
Leflunomide can cause serious birth defects and is strictly contraindicated during pregnancy. Women of reproductive age need a negative pregnancy test before starting the drug. What makes leflunomide unusual compared to many other medications is how long its active ingredient lingers in the body. The drug’s breakdown product can stay in your system for months, even up to two years, after you stop taking it. If you’re planning a pregnancy or become pregnant unexpectedly, a medical washout procedure using a separate medication can speed up elimination of the drug from your body. Blood tests then confirm the drug has dropped to safe levels before conception.
This long clearance time also applies to men. If you or your partner are considering pregnancy, it’s essential to plan ahead and discuss timing with a healthcare provider well before stopping the medication.
How It Compares to Methotrexate
Methotrexate is the most commonly prescribed DMARD for rheumatoid arthritis, and leflunomide is often considered when methotrexate isn’t tolerated or doesn’t work well enough. In head-to-head clinical trials, the two drugs showed similar effectiveness for controlling RA symptoms. Some side effects differ between them: diarrhea and hair thinning are more common with leflunomide, while methotrexate is more often associated with nausea and mouth sores. Leflunomide is taken as a daily pill, whereas methotrexate is typically taken once a week, either as a pill or injection. In some cases, the two are prescribed together for more aggressive disease, though this combination requires especially close liver monitoring.