PT  - JOURNAL ARTICLE
AU  - D L Scott
AU  - J S Smolen
AU  - J R Kalden
AU  - L B A van de Putte
AU  - A Larsen
AU  - T K Kvien
AU  - M Schattenkirchner
AU  - P Nash
AU  - C Oed
AU  - I Loew-Friedrich
TI  - Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine
AID  - 10.1136/ard.60.10.913
DP  - 2001 Oct 01
TA  - Annals of the Rheumatic Diseases
PG  - 913--923
VI  - 60
IP  - 10
4099  - http://ard.bmj.com/content/60/10/913.short
4100  - http://ard.bmj.com/content/60/10/913.full
SO  - Ann Rheum Dis2001 Oct 01; 60
AB  - OBJECTIVE Recent studies have demonstrated the short term efficacy of leflunomide. This study evaluates the efficacy and safety of leflunomide and sulfasalazine in rheumatoid arthritis over a two year follow up period.METHODS 358 patients with rheumatoid arthritis in a double blind trial were randomly allocated to receive either leflunomide 20 mg/day, placebo, or sulfasalazine 2 g/day. Those completing six months of treatment (n=230) were given the option to continue in 12 (n=168) and 24 (n=146) month double blinded extensions; the placebo group switched to sulfasalazine. This report compares efficacy and safety of leflunomide with sulfasalazine in the 6, 12, and 24 month patient cohorts.RESULTS The efficacy seen at six months was maintained at 12 and 24 months. Twenty four month cohorts on leflunomide showed significant improvement compared with sulfasalazine in doctor (−1.46 v−1.11, p=0.03) and patient (−1.61 v−1.04, p<0.001) global assessments, ACR20% response (82%v 60%, p<0.01), and functional ability (Δmean HAQ −0.65 v −0.36, p=0.0149; ΔHAQ disability index −0.89 v −0.60, p=0.059). Improvement in other variables was comparable for the two drugs, including slowing of disease progression. Improved HAQ scores in 6, 12, and 24 month leflunomide cohorts were seen in both non-responders (24%, 29%, 35%, respectivelyv sulfasalazine 8%, 10%, 27%) and ACR20% responders (leflunomide 63%, 62%, 66% vsulfasalazine 50%, 64%, 44%). Leflunomide is well tolerated at doses of 20 mg. No unexpected adverse events or late toxicity were noted during the two year period. Diarrhoea, nausea, and alopecia were less frequent with continued treatment.CONCLUSION These long term data confirm that leflunomide is an efficacious and safe disease modifying antirheumatic drug.