The Combination of Leflunomide (Arava®) and Methotrexate

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Leflunomide

Abstract #1216­948 The Combination of Leflunomide (Arava®) and Methotrexate

(MTX) in Patients with Active Rheumatoid Arthritis (RA) who are Failing on

MTX Treatment Alone: A Double­Blind Placebo Controlled Study J Kremer, J

Caldwell, G Cannon, M Genovese, J Cush, J Bathon, J . Baltimore and

Kansas City.

Patients with active RA while on MTX (mean dose = 16­17 mg/wk) were

randomized to receive leflunomide (LEF) or placebo (PL). Dosing of

leflunomide was 100 mg loading dose followed by 10 mg qd with option to

increase to 20 mg qd. The ACR20 response rates at 24 weeks (defined as the

primary endpoint) were 46.2% for the LEF + MTX group and 19.5% for the PLC +

MTX group. Using the last observation carried forward (LOCF) methodology,

the ACR 20, 50 and 70 responses for LEF + MTX were 51.5%, 26.2% and 10.0%,

respectively, vs 23.3%, 6.0%, and 2.3%, respectively, for PLC + MTX. Drug

related adverse events included diarrhea (22% for LEF + MTX vs 10% for PL +

MTX), nausea and dizziness. Increases in LFTs of > 3XULN at any time during

the 24 week treatment period for ALT and AST were uncommon (2.3% and 1.5%

for LEF + MTX vs 0.8% and 0.0% for PL + MTX).

Editorial Comments: The addition of leflunomide to MTX in a patient who has

responded inadequately to MTX, confers a significant advantage over MTX

alone and the combination is well tolerated. These results are encouraging

since there was concern at the outset that hepatic toxicity would be higher

given the fact that both MTX and LEF are potentially hepatotoxic.

http://www.hopkins-arthritis.som.jhmi.edu/edu/acr2000/ra-treatments.html