Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group.

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.

FINDINGS:

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 significantly 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.

INTERPRETATION:

Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.

• Authors: J S Smolen, J R Kalden, D L Scott, B Rozman, T K Kvien, A Larsen, I Loew-Friedrich, C Oed, R Rosenburg
• Journal: Lancet (London, England) (Lancet) Vol. 353 Issue 9149 Pg. 259-66 (Jan 23 1999) ISSN: 0140-6736 [Print] England
• PMID: 9929017 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Immunosuppressive Agents
• Isoxazoles
• Placebos
• Sulfasalazine
• Leflunomide

Topics

• Algorithms
• Analysis of Variance
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (diagnostic imaging, drug therapy)
• Disease Progression
• Double-Blind Method
• Female
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Isoxazoles (adverse effects, therapeutic use)
• Leflunomide
• Male
• Middle Aged
• Placebos
• Radiography
• Statistics, Nonparametric
• Sulfasalazine (therapeutic use)
• Treatment Outcome