What is leflunomide?
Leflunomide (brand name Arava) is an oral medication classified as a disease-modifying antirheumatic drug (DMARD). DMARDs work differently from typical painkillers or nonsteroidal anti-inflammatory drugs (NSAIDs) because they address the root cause of certain conditions by suppressing the immune system, rather than just alleviating symptoms. This action is particularly useful for autoimmune diseases where the body’s immune system mistakenly attacks its own tissues, causing chronic inflammation and damage. By calming the immune system, leflunomide helps to reduce joint pain, swelling, and stiffness, and can also help slow the progression of joint damage over time. It is a potent drug that requires a prescription and regular medical supervision.
How leflunomide works
As an immunosuppressive agent, leflunomide inhibits the function of specific immune cells, especially activated lymphocytes. After oral administration, leflunomide is converted in the body into its active metabolite, known as A77 1726 or teriflunomide. This active form works primarily by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which is crucial for de novo pyrimidine synthesis. Pyrimidines are building blocks of DNA and RNA, and activated lymphocytes, unlike most other cells, heavily rely on this de novo pathway for their rapid proliferation. By inhibiting DHODH, leflunomide prevents these immune cells from multiplying effectively, thereby suppressing the overactive immune response that drives autoimmune diseases.
Conditions treated with leflunomide
Leflunomide is primarily used to treat inflammatory autoimmune conditions, helping to reduce inflammation and prevent further joint damage.
Rheumatoid Arthritis (RA)
Leflunomide is widely used for adults with moderate to severe active rheumatoid arthritis. RA is a chronic inflammatory disorder that causes the immune system to attack the linings of the joints on both sides of the body. Symptoms include pain, swelling, and stiffness, which can lead to progressive joint damage and loss of function if not controlled. Leflunomide helps to slow down the progression of RA and improve physical function. It can be used alone or in combination with other DMARDs, such as methotrexate, to achieve better disease control.
Psoriatic Arthritis (PsA)
While not specifically FDA-approved for psoriatic arthritis, leflunomide is a commonly recommended treatment for PsA due to its similar mechanism of action and proven effectiveness. PsA is a form of inflammatory arthritis that affects some people with the skin condition psoriasis. It causes joint pain, stiffness, and swelling, often affecting the distal joints of the fingers and toes, as well as the spine. Studies have shown that leflunomide can significantly improve both joint and skin symptoms in patients with PsA.
Important considerations and monitoring
Due to its potential for serious side effects, taking leflunomide requires careful consideration and regular monitoring by a healthcare provider.
Regular blood tests
- Liver function tests (LFTs): Leflunomide can cause liver damage, and in rare cases, liver failure. Regular monitoring of liver enzyme levels is essential. Typically, these tests are performed monthly for the first six months and then quarterly thereafter.
- Blood cell counts: The drug can cause bone marrow suppression, leading to low white blood cell counts (increasing infection risk) and low platelet counts (increasing bleeding risk). Complete blood counts (CBCs) should also be monitored regularly.
Contraindications and precautions
- Pregnancy: Leflunomide is contraindicated in pregnancy due to the risk of fetal harm. Women of childbearing potential must use reliable contraception. Due to its long half-life, the drug can stay in the body for up to two years after stopping treatment. A drug elimination procedure may be necessary before attempting to conceive.
- Liver disease: Patients with pre-existing liver disease or elevated liver enzymes should not take leflunomide. Alcohol consumption should also be avoided due to the increased risk of liver damage.
- Severe infections: The immunosuppressive nature of leflunomide can increase susceptibility to infections. It is not recommended for patients with active, severe infections.
Comparison of leflunomide and methotrexate
Both leflunomide and methotrexate are commonly used DMARDs for rheumatoid arthritis, but they have key differences. The choice between them depends on the patient's specific health profile, tolerance, and other medications. For more detailed information, consult the American College of Rheumatology.
| Feature | Leflunomide (Arava) | Methotrexate (Otrexup, Rasuvo) |
|---|---|---|
| Mechanism | Inhibits dihydroorotate dehydrogenase (DHODH), blocking pyrimidine synthesis. | Inhibits dihydrofolate reductase, affecting folic acid metabolism and suppressing immune cell proliferation. |
| Administration | Oral tablet, typically taken once per day. | Oral tablet or injection, typically taken once per week. |
| Primary Uses | Rheumatoid arthritis and psoriatic arthritis. | Rheumatoid arthritis, certain cancers, psoriasis, and more. |
| Half-Life | Very long, can remain in the body for up to 2 years. | Shorter half-life, does not require a special elimination procedure for typical use. |
| Liver Risk | Risk of liver damage, requiring regular monitoring. Increased risk with pre-existing liver disease or alcohol use. | Risk of liver toxicity, typically mitigated with folic acid supplementation and monitoring. |
| GI Side Effects | Diarrhea is a common side effect. | Nausea and stomach upset are common, can be reduced with folic acid. |
Conclusion
Leflunomide is a valuable DMARD for managing chronic inflammatory conditions like rheumatoid and psoriatic arthritis by suppressing the overactive immune cells responsible for inflammation. While it offers significant benefits in controlling disease activity and preventing joint damage, its use requires careful medical supervision, particularly regarding potential liver damage and serious infections. Patients must adhere to regular monitoring schedules and discuss any concerns with their healthcare provider to ensure safe and effective treatment. For individuals who cannot tolerate other DMARDs like methotrexate, leflunomide can be an effective alternative.
