From the Guidelines
Leflunomide is an immunosuppressive disease-modifying antirheumatic drug (DMARD) primarily used to treat rheumatoid arthritis, psoriatic arthritis, and occasionally other autoimmune conditions, with a recommended dosing regimen and monitoring strategy as outlined in recent guidelines 1.
Key Points
- The standard dosing regimen typically begins with a loading dose of 100 mg daily for 3 days, followed by a maintenance dose of 10-20 mg once daily, as supported by recent evidence 1.
- Leflunomide works by inhibiting dihydroorotate dehydrogenase, an enzyme involved in pyrimidine synthesis, which reduces proliferation of activated lymphocytes that drive autoimmune inflammation.
- Common side effects include diarrhea, hair loss, elevated liver enzymes, and increased risk of infections, highlighting the need for regular blood monitoring, including liver function tests every 1-3 months 1.
- Leflunomide has a very long half-life (approximately 2 weeks), so a cholestyramine washout procedure may be necessary if rapid drug elimination is needed.
- The medication is contraindicated in pregnancy (category X) and requires effective contraception during treatment and for up to 2 years after discontinuation unless a drug elimination procedure is performed.
Clinical Use
- Leflunomide is considered a first-line treatment option for patients with rheumatoid arthritis who have a contraindication to methotrexate or experience early intolerance to methotrexate, as recommended by the European League Against Rheumatism (EULAR) 1.
- The American College of Rheumatology also provides guidelines for the use of leflunomide in the treatment of juvenile idiopathic arthritis, including recommendations for medication monitoring and dosing adjustments 1.
Monitoring and Safety
- Regular monitoring of liver function tests, complete blood counts, and renal function is essential to minimize the risk of adverse effects, as emphasized in recent guidelines 1.
- The use of folic or folinic acid is recommended in conjunction with leflunomide to reduce the risk of gastrointestinal and hepatic adverse effects.
From the FDA Drug Label
Leflunomide is indicated in adults for the treatment of active rheumatoid arthritis (RA): to reduce signs and symptoms to inhibit structural damage as evidenced by X-ray erosions and joint space narrowing to improve physical function The use of Leflunomide is for the treatment of active rheumatoid arthritis (RA) in adults, to:
- Reduce signs and symptoms
- Inhibit structural damage
- Improve physical function 2
From the Research
Use of Leflunomide
- Leflunomide is a disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis (RA) 3, 4, 5, 6, 7.
- It is considered a second-line treatment option for RA, used when patients fail to respond to other treatments or have contraindications to other DMARDs 3, 6.
- Leflunomide works by inhibiting the growth of activated lymphocytes, which are involved in the inflammation and joint damage associated with RA 4, 5.
- The drug is initiated with a loading dose of 100mg for 3 days, followed by a daily dose of 20mg 4, 5, 6, 7.
- Leflunomide has been shown to be effective in reducing the signs and symptoms of RA, inhibiting structural damage, and improving physical function 4, 5, 7.
- The drug has a rapid onset of action, with benefits evident within 4 weeks, and sustained efficacy for up to 24 months 5, 7.
- Leflunomide can be used as monotherapy or in combination with other DMARDs, such as methotrexate 6, 7.
- Common adverse events associated with leflunomide include diarrhea, respiratory infections, nausea, headache, rash, and elevated liver enzymes 4, 5, 6.