Journal List > J Rheum Dis > v.20(3) > 1064036

Joo, Park, Kwon, and Lim: Safety and Efficacy Evaluation for the Addition of Either Etanercept or Leflunomide in Korean Rheumatoid Arthritis Patients Inadequately Responding to Methotrexate

Abstract

Objective

To compare the safety and efficacy associated with the addition of etanercept (ETN) with that of leflunomide (LEF) in Korean rheumatoid arthritis (RA) patients, who inadequately respond to methotrexate (MTX) in a randomized, open-label study.

Methods

Twenty-nine subjects suffering moderate to severe RA, despite MTX treatment were randomly assigned to a combination therapy with either ETN or LEF. The primary end-point was the proportion of subjects achieving American College of Rheumatology (ACR20) criteria at week 16.

Results

Ninety percent (n=18) of the ETN+MTX group (n=20) and 22.2% (n=2) of the LEF+MTX group (n=9) ach-ieved an ACR20 response (p=0.001). All patients (n=20) in the ETN+MTX group showed moderate or good EULAR response as compared with 55.6% (n=5) in the LEF+MTX group (p=0.012). All of the ETN+MTX subjects completed the study without adverse events. Adverse events occurred in 77.8% (n=7) of cases in the LEF+MTX group; sig-nificantly elevated serum AST/ALT levels in 6 subjects and mild neutropenia (ANC < 1,500/μ L) in 1 subject.

Conclusion

The ETN+MTX combination therapy was effective and safe, whereas the LEF+MTX combination therapy resulted in moderate efficacy in only half of the cases, and was accompanied by a high rate of adverse events. Elevated AST/ALT was the most common adverse event causing dose adjustment or discontinuation of therapeutic agent in the LEF+MTX group.

References

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Figure 1.
Patient disposition. LEF: lefunomide, MTX: methotrexate, ETN: etanercept, LFT: liver function test, ACR: American College of Rheumatology, EULAR: European League Against Rheumatism. ∗p=0.001, p=0.012, p<0.001. Fisher's exact test.
jrd-20-166f1.tif
Figure 2.
ACR20 and EULAR response rate at 16 weeks (∗p=0.001, p=0.012. Fisher's exact test).
jrd-20-166f2.tif
Table 1.
Baseline demographics and characteristics of both patient groups.
  LEF+MTX (n=9) ETN+MTX (n=20)  
Age (years) 54.6±6.6 50.0±10.6 p=0.229
Female, n (%) 9 (100) 18 (90) p=1.000
Duration of disease (years) 20.8±13.7 8.4±4.8 p=0.018
BMI 23.3±3.7 21.8±2.6 p=0.555
Height (cm) 153.9±5.9 157.8±8.7 p=0.239
Weight (kg) 54.1±8.9 55.1±7.4 p=0.588
DM (%) 2 (22.2) 0 p=0.089
Liver disorder, n (%) 0 0  
Use of NSAIDS, n (%) 6 (66.7) 16 (80) p=0.642
Use of INH, n (%) 3 (33.3) 13 (65) p=0.226
Drinking alcohol, n (%) 4 (44.4) 5 (25.0) p=0.295
Daily prednisolone (mg) 3.9±1.8 3.8±2.4 p=0.782
Weekly methotrexate (mg) 16.4±4.5 14.3±3.6 p=0.219
DAS28-ESR 6.85±1.10 6.41±0.97 p=0.346

All values are mean± SD unless otherwise specified. LEF: lefunomide, MTX: methotrexate, ETN: etanercept, BMI: body mass index, DM: diabetes mellitus, NSAIDS: nonsteroidal antiinflammatory drugs, INH: isoniazid, DAS28: disease activity score based on a 28-joint count, ESR: erythrocyte sedimentation rate. The Mann-Whitney U test was used to compare the variables

Table 2.
Characteristics of patients in the LEF+MTX treatment group
Patient number Age (years) Disease duration (years) PD daily dose (mg) MTX weekly dose (mg) LEF daily dose (mg) Adverse event
1 56 12 5 12.5 20 AST/ALT 256/402
2 63 45 5 20 20 AST/ALT 61/70
3 47 8 5 20 10 AST/ALT 53/52
4 64 13 5 10 10 No adverse event
5 46 6 5 20 10 AST/ALT 28/48
6 50 13 0 20 10 Neutropenia (ANC 1,443/μ L)
7 53 26 2.5 10 10 AST/ALT 58/35
8 52 37 5 20 10 AST/ALT 75/81
9 60 27 2.5 15 10 No adverse event

PD: prednisolone, MTX: methotrexate, LEF: leflunomide, ANC: absolute neutrophil count, AST: aspartate aminotransferase, ALT: alanine aminotransferase, AST upper normal limit 38 IU/L, ALT upper normal limit 43 IU/L

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