Ann Rheum Dis 2001;60:913-923 ( October )

Extended report

Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine D L Scott^a, J S Smolen^b, J R Kalden^c, L B A van de Putte^d, A Larsen^e, T K Kvien^f, M Schattenkirchner^g, P Nash^h, C Oedⁱ, I Loew-Friedrich^{i *}, for the European Leflunomide Study Group

^a King's College Hospital, London, UK, ^b University of Vienna, Vienna, Austria, ^c University Erlangen-Nuremberg, Erlangen, Germany, ^d University Hospital Nijmegen, Nijmegen, The Netherlands, ^e Kongsvinger Sjukehus, Kongsvinger, Norway, ^f Diakonhjemmet Hospital, Oslo, Norway, ^g University of Munich, Munich, Germany, ^h Sixth Avenue Specialist Centre, Queensland, Australia, ⁱ Aventis Pharma

Correspondence to: Professor D L Scott, King's College Hospital, East Dulwich Grove, Dulwich, London SE22 8PT, UK leigh.joyce{at}kcl.ac.uk

Accepted for publication 6 March 2001

OBJECTIVERecent 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.
METHODS358 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.
RESULTSThe 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 (mean HAQ 0.65 v 0.36, p=0.0149; HAQ 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%, respectively v sulfasalazine 8%, 10%, 27%) and ACR20% responders (leflunomide 63%, 62%, 66% v sulfasalazine 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.
CONCLUSIONThese long term data confirm that leflunomide is an efficacious and safe disease modifying antirheumatic drug.

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^* Members of the European Leflunomide Study Group are given in the appendix.

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© 2001 by Annals of the Rheumatic Diseases
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