A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis

被引:341
|
作者
Emery, P
Breedveld, FC
Lemmel, EM
Kaltwasser, JP
Dawes, PT
Gömör, B
Van den Bosch, F
Nordström, D
Bjorneboe, O
Dahl, R
Horslev-Petersen, K
de la Serna, AR
Molloy, M
Tikly, M
Oed, C
Rosenburg, R
Loew-Friedrich, I
机构
[1] Univ Leeds, Sch Med, Dept Rheumatol & Rehabil, Leeds LS2 9NZ, W Yorkshire, England
[2] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands
[3] Staatl Rheumakrankenhaus, Baden, Switzerland
[4] Univ Frankfurt, D-6000 Frankfurt, Germany
[5] Staffordshire Rheumatol Ctr, Stoke On Trent, Staffs, England
[6] Natl Inst Rheumatol & Physiotherapy, Budapest, Hungary
[7] Natl Inst Rheumatol & Physiotherapy, Budapest, Hungary
[8] State Univ Ghent Hosp, Dept Rheumatol, Ghent, Belgium
[9] Univ Helsinki, Cent Hosp, Dept Rheumatol, Helsinki, Finland
[10] Martina Hansens Hosp, Dept Rheumatol, Sandvika, Norway
[11] Univ Uppsala Hosp, Dept Internal Med, S-75185 Uppsala, Sweden
[12] Hvidovre Univ Hosp, Dept Med, Res Lab, Copenhagen, Denmark
[13] Hosp Sant Pau, Barcelona, Spain
[14] Univ Coll Hosp, Cork, Ireland
[15] Chris Hani Baragwanath Hosp, Johannesburg, South Africa
[16] Hoechst Marion Roussel, Frankfurt, Germany
关键词
leflunomide; methotrexate; clinical trial; folate supplementation; rheumatoid arthritis; radiographic assessment of disease progression;
D O I
10.1093/rheumatology/39.6.655
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). Methods. In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. Results. After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr. 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes rs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate ps no drug-related deaths among the subjects receiving leflunomide. Conclusions. Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.
引用
收藏
页码:655 / 665
页数:11
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