Leflunomide, known by the brand name Arava, is a prescription medication belonging to the class of drugs called disease-modifying antirheumatic drugs (DMARDs). Its primary function is to suppress the overactive immune system that is characteristic of certain autoimmune diseases. By doing so, it helps reduce inflammation and swelling, slow the progression of joint damage, and improve physical function in affected patients.
Primary Medical Conditions Treated with Leflunomide
The most prominent medical conditions for which leflunomide is used include rheumatoid arthritis (RA) and psoriatic arthritis (PsA). While RA is the primary FDA-approved indication, its use for PsA is also common and effective.
Leflunomide for Rheumatoid Arthritis (RA)
Rheumatoid arthritis is a chronic autoimmune disorder in which the body's immune system mistakenly attacks the lining of the joints, causing painful swelling that can eventually lead to bone erosion and joint deformity. Leflunomide is indicated for adults with moderate to severe active RA. In RA treatment, leflunomide is used to:
- Reduce the signs and symptoms of RA, such as joint pain, stiffness, and swelling.
- Slow down the progression of structural damage to the joints, which is visible on X-rays.
- Improve overall physical function and quality of life.
Leflunomide for Psoriatic Arthritis (PsA)
Psoriatic arthritis is a type of inflammatory arthritis that affects some people who have psoriasis, a condition characterized by scaly skin patches. PsA causes joint inflammation, stiffness, and swelling, similar to RA. Though not its primary FDA-approved use, leflunomide is a conventional DMARD often prescribed for PsA and has been shown to be effective in treating both the joint and skin manifestations of the disease.
How Leflunomide Works: The Mechanism of Action
Unlike nonsteroidal anti-inflammatory drugs (NSAIDs), which only treat symptoms, leflunomide addresses the root cause of the inflammatory process. Once ingested, leflunomide is metabolized into its active form, teriflunomide. This active metabolite inhibits a key mitochondrial enzyme called dihydroorotate dehydrogenase (DHODH). By inhibiting DHODH, leflunomide blocks the de novo synthesis of pyrimidine, a building block necessary for DNA and RNA replication.
- Targets Proliferating Immune Cells: The inhibition of pyrimidine synthesis primarily affects rapidly dividing immune cells, such as T-cells, which are responsible for the inflammation seen in RA and PsA.
- Spares Non-Immune Cells: Non-lymphoid cells can use a different metabolic pathway (the salvage pathway) for pyrimidine synthesis, which makes them less sensitive to leflunomide's effects. This targeted action helps explain why the drug is effective at suppressing the immune system without causing widespread harm to other body tissues.
Important Considerations and Monitoring
Starting leflunomide requires careful consideration and regular monitoring by a healthcare provider due to potential side effects and health risks.
Before starting treatment, your doctor will check for:
- Pre-existing liver or kidney disease
- Active infections, including tuberculosis (TB)
- High blood pressure
- Pregnancy status (as it is contraindicated in pregnancy and carries a high risk of fetal harm)
Common side effects may include:
- Diarrhea or other gastrointestinal upset
- Nausea
- Rash
- Hair thinning or hair loss
- Headache
- High blood pressure
- Elevated liver enzymes (requires regular monitoring)
For ongoing management, patients are regularly monitored with blood tests to check liver enzyme levels and blood counts, especially in the first several months of treatment.
Comparison: Leflunomide vs. Methotrexate
Leflunomide is often compared to methotrexate (MTX), another first-line DMARD for RA. While both are effective, they have distinct differences.
| Feature | Leflunomide (Arava) | Methotrexate (MTX) |
|---|---|---|
| Mechanism | Inhibits pyrimidine synthesis. | Inhibits purine synthesis and other metabolic pathways. |
| Dosage | Oral tablets, typically taken once a day. | Oral tablets or injections, typically taken once a week. |
| Onset | May take 4-12 weeks for full effect. | Similar onset, but can vary. |
| Side Effects | Diarrhea, rash, hair loss, elevated liver enzymes. | Nausea, mouth sores, low white blood cells, elevated liver enzymes. |
| Pregnancy Risk | Very high risk (Category X); requires extensive washout period. | High risk; requires contraception. |
| Cost | Can be more expensive than generic MTX. | Considered more cost-effective as a generic. |
Conclusion
In summary, leflunomide is a powerful DMARD primarily used to treat active rheumatoid arthritis and psoriatic arthritis. By inhibiting the immune system's attack on the joints, it helps control disease symptoms and prevent long-term damage. While it offers significant benefits for patients with these chronic inflammatory conditions, its use requires careful medical supervision, particularly regarding liver function and pregnancy risk. For a detailed understanding of the drug's approved uses and safety information, consult the prescribing information from the U.S. Food and Drug Administration (FDA).
This article is for informational purposes only and does not constitute medical advice. Please consult with a healthcare professional for personalized guidance regarding treatment options.
