Leflunomide is a disease-modifying antirheumatic medication that inhibits de novo pyrimidine synthesis. Approved for the treatment of rheumatoid arthritis, it has more recently been studied for the treatment of psoriatic arthritis and psoriasis.

In a large randomized double-blind placebo-controlled trial of 182 patients with both psoriasis and psoriatic arthritis, patients were randomized to placebo or leflunomide at 20 mg daily for 24 weeks. Subjects had a baseline body surface area of psoriasis involvement that was greater than 3% and were allowed concurrent use of low-dose systemic corticosteroids for the treatment of their psoriatic arthritis (15% of the leflunomide-treated group). After 24 weeks of treatment, 17% of the leflunomide-treated subjects achieved a PASI 75 versus 8% of those receiving placebo (P = .048) and 59% of the patients treated with leflunomide and 30% of the patients treated with placebo (P<.001) were responders by the Psoriatic Arthritis Response Criteria.¹⁶³

Potential toxicities caused by leflunomide are predominantly gastrointestinal irritation (diarrhea, nausea, dyspepsia), but also include elevated liver enzymes, leukopenia, drug eruption, headaches, increased risk of infections,¹⁶⁴ and teratogenicity. In the randomized double-blind placebo-controlled trial of leflunomide for psoriasis and psoriatic arthritis, side effects that occurred at a higher frequency in the leflunomide group than the placebo group included diarrhea, elevated AST levels, lethargy, and leukopenia.¹⁶³ 

References

163. Kaltwasser JP, Nash P,Gladman D, Rosen CF, Behrens F, Jones P, et al. Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 2004;50:1939-50.
164. Prakash A, Jarvis B.Leflunomide: a review of its use in active rheumatoid arthritis. Drugs 1999;58:1137-64.

Loading dose of 100mg/d for 3 days followed by 20 mg/d long term.

• In the only randomized controlled trial of 190 patients, 24 wk of leflunomide, dosed as above, led to a PASI 75 of 17% vs placebo response of 8% (P = .048)

• Not reported

• Most common side effects include nausea, diarrhea, loss of appetite, weight loss, headache, dizziness.
• Less frequent adverse reactions may include severe liver injury, including fatal outcome. Most cases of severe liver injury occur within 6 mo of therapy and in patients with multiple risk factors for hepatotoxicity.
• There are rare reports of pancytopenia, agranulocytosis, and thrombocytopenia in patients receiving leflunomide. This occurs in patients who have been treated with methotrexate or other immunosuppressive agents, or who had recently discontinued these.

• Co-administration of leflunomide with methotrexate demonstrates no pharmacokinetic interaction between the two drugs but can lead to an increased risk of hepatotoxicity.
• When leflunomide is given with rifampin, leflunomide levels are increased.

• History and physical examination
• CBC count/diff and LFTs
• Pregnancy test if indicated

• Monthly CBC count with differential and LFTs for the first 6 mo and then every 6-8 wk
• Pregnancy testing if indicated

• Category X

• Leflunomide should not be used by nursing mothers.

• No data

• In the only randomized controlled study of 190 patients with psoriasis and psoriatic arthritis, 59% of patients treated with leflunomide vs 30% of patients treated with placebo were responders by the PsARC