Reappraisal of the clinical use of leflunomide in rheumatoid arthritis and psoriatic arthritis

Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been in routine clinical use for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis for a decade. In RA, clinical trials of up to two years’ duration showed that leflunomide monotherapy was equivalent to methotrexate in clinical and radiographic disease outcomes (tender and swollen joint counts, physician and patient global assessments, American College of Rheumatology and Disease Activity Score responses, slowing or halting of radiographic progression). In a number of studies, quality of life measurements indicated that leflunomide is superior to methotrexate. Leflunomide has been studied in combination with methotrexate and shows efficacy in patients only partly responsive to this agent. Recent trials have shown that leflunomide can be used safely with biologic DMARDs, including antitumor necrosis factor agents and rituximab as part of the treatment algorithm in place of methotrexate as a cotherapy. Leflunomide has demonstrated efficacy as a monotherapy in psoriatic arthritis, and it also has a beneficial effect in psoriasis. Postmarketing studies have shown that retention on treatment with leflunomide is equal to methotrexate and superior to other DMARDs. In general, its side effect profile is acceptable compared with other DMARDS, with nausea, diarrhea, and hair fall occurring commonly, but only rarely leading to discontinuation. Liver toxicity is the most significant problem in clinical use although it is uncommon. Peripheral neuropathy, hypertension, pneumonitis, and cytopenia occur more rarely. Leflunomide is contraindicated in pregnancy and should be used with caution in women during child-bearing years. In this review, the place of leflunomide in therapy is discussed and practical advice informed by evidence is given regarding dosing regimens, safety monitoring, and managing side effects. Leflunomide remains one of the most useful of the nonbiologic DMARDs.