Author/Editor		Smolen, Josef S; Kalden, Joachim R; Scott, David L; Rozman, Blaž; Kvien, Tore K; Larsen, Arvi; Loew-Friedrich, Iris; Oed, Christine; Rosenburg, Ronald
Title		Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial
Type		članek
Source		Lancet
Vol. and No.		Letnik 353, št. 9149
Publication year		1999
Volume		str. 259-66
Language		eng
Abstract		Background Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. Methods 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. Fndings The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were signifićantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. Interpretatlon Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar effcacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a diseasemodifying antirheumatic drug.
Descriptors		ARTHRITIS, RHEUMATOID SULFASALAZINE ISOXAZOLES DOUBLE-BLIND METHOD MULTICENTER STUDIES IMMUNOSUPPRESSIVE AGENTS TREATMENT OUTCOME JOINTS PHYSICAL EXAMINATION RHEUMATOID FACTOR