Efficacy and Safety of Leflunomide and Methotrexate in Treating Rheumatoid Arthritis: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

SU Ran ¹ ,  WEI Li ¹ , CHEN Yanchun ² , LIU Yu ³

1. Department of Rheumatism, the First Affiliated Hospital of Xinjiang Medical University, Urumuqi 830054, China;2. Department of Cadre, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China;3. Evidence-based Medicine Center, the First Affiliated Hospital of Xinjiang Medical University, Urumuqi 830054, China;

Corresponding author：

WEI Li, Email: weilifengshike@163.com

Keywords：

Leflunomide; Methotrexate; Rheumatoid arthritis; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.20110177

Video：

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Objective 　To evaluate the efficacy and safety of Leflunomide (LEF) in the treatment of Rheumatoid Arthritis (RA), so as to provide scientific proof for applying LEF in China.
Methods 　Randomized controlled trials (RCTs) about the effect of LEF on patients with RA from January 1989 to January 2011 were searched from the following databases, CNKI, WanFang Data, MEDLINE, EMbase and CBM. After two reviewers independently screened the studies according to the inclusion and exclusion criteria, extracted the data and assessed the quality, the data were analyzed by RevMan 5.0 software.
Results 　Among 3247 patients in 16 included RCTs, 1711 patients were in the LEF group, while the other 1536 patients were in the Methotrexate (MXT) group. The results of meta-analyses showed there was no significant difference in the efficacy between LEF and MXT (RR=1.03, 95%CI 0.94 to 1.11, P gt;0.05), but a significant difference was found in the side reaction (RR=0.67, 95%CI 0.49 to 0.94, P lt;0.05).
Conclusion 　Based on the current studies, Leflunomide is as effective as the commonly-used Methotrexate in the treatment of rheumatiod arthritis at present, much safer than Methotrexate, and thought as a safe and effective SAARD. For the quality restrictions of the included studies, more double blind RCTs with high quality are required to further assess the effects.

Citation： SU Ran,WEI Li,CHEN Yanchun,LIU Yu. Efficacy and Safety of Leflunomide and Methotrexate in Treating Rheumatoid Arthritis: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2011, 11(9): 1062-1069. doi: 10.7507/1672-2531.20110177 Copy

1.	1 Barlett RR, Anagnostopulos H, Zielinski T, et al . Effects of leflunomide on immune responses and models of inflammation. Springer Semin Immunopathal , 1993, 14(4): 381-394.
2.	Mldenovic V, Domljan Z, Rozman B, et al . Safety and effectiveness of leflunomide in the treatment of patients with rheumatoidarthritis. Arthritis Rheumat , 1995, 38(11): 1596-1603.
3.	Smolen JS, Kalden JR, Scott DL, et al . Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoidarthritis: a double-blind, randomised, multicentre trial. Lancet , 1999, 353(9149): 259-266.
4.	Felson DT, Anderson JJ, Boers M, et al . American college of rheumatology preliminary definition of improvement in rheumatoid arthrit is. Arthritis Rheumat , 1995, 38(6): 727-735.
5.	孙凌云, 金欧, 王红. 来氟米特治疗类风湿关节炎的疗效评价. 南京大学学报(自然科学), 2002, 38(5): 632-635.
6.	Jadad AR, Moore RA, Corral D, Assessing the quality of the reports of randomized clinical trials: is blinding necessary? control clin trials , 1996, 17(1): 1-12.
7.	吕随峰, 肖飞, 何培根, 等. 爱若华治疗类风湿性关节炎的疗效及其安全性. 临床内科杂志, 2000, 11(6): 375-376.
8.	李向培, 厉小梅, 汪国生, 等. 来氟米特治疗类风湿性关节炎的临床研究. 中国临床药理学与治疗学, 200l, 6 (2): 142-144.
9.	张玲玲, 丁长海, 梁朝朝, 等. 来氟米特治疗类风湿关节炎随机双盲平行对照临床试验. 中国临床药理学杂志, 2005, 9, (97): 341-343.
10.	Hu Y, Tu S, Liu P. A randomized, controlled, single-blind trial of leflunomide in the treatment of rheumatoid arthritis. J Tongji Med Univ , 2001, 21(1): 72-74.
11.	钟清, 甘华, 陈恩静, 等. 来氟米特治疗类风湿性关节炎的临床疗效评价. 重庆医科大学学报, 2003, 28 (4): 503-505, 524.
12.	帅宗文, 刘爽, 孙桂华, 等. 来氟米特治疗类风湿性关节炎的Ⅱ期临床试验. 安徽医科大学学报, 2002, 37 (1): 41-43.
13.	姜林锑, 於强, 梅振武. 来氟米特治疗类风湿性关节炎的疗效评价. 中国临床医学, 2000, 7 (4): 413-415.
14.	马骥良. 来氟米特和甲氨喋呤治疗活动性类风湿关节炎的对比观察. 北京医学, 2000, 22 (6): 342-345.
15.	Strand V, Cohen S, Schiff M, et al . Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch Intern Med , 1999, 159 (21): 2542-2550.
16.	Fiehn C, Jacki S, Heilig B, et al . Eight versus 16-week re-evaluation period in rheumatoid arthritis patients treated with leflunomide or methotrexate accompanied by moderate dose prednisone. Rheumatol Int , 2007, 8(27): 975–979.
17.	Bao C, Chen S, Gu Y, et al . Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial. Chin Med J (Engl) , 2003, 116(8): 1228-1234.
18.	Emery P, Breedveld FC, Lemmel EM, et al . A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology , 2000, 39: 655-665.
19.	Cohen S, Cannon GW, Schiff M, et al . Two-year, blinded, randomized, controlled trail of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Arthritis Rheum , 2001, 44(9): 1984-1992.
20.	Ishaq M, Muhammad JS, Hameed K, et al . Leflunomide or methotrexate? Comparison of clinical efficacy and safety in low socio-economic rheumatoid arthritis patients. Mod Rheumatol , 2011, 1(7): 566-589.
21.	Peter T, George W, Andreas M, et al . Clinical improvement as peflected in measures of function and health-related quality of life following treatment with leflunomide compare wirh methotrexate in patients with rheumatoid arthritis. Arthritis & Rheumatism , 2000, 3(43): 506–514.
22.	Katayama K, Matsuno T. Long-term efficacy of leflunomide on disease activity and inhibition of joint damage: retrospective comparison with methotrexate for Japanese rheumatoid arthritis patients. Mod Rheumatol , 2009, 6(19): 513–521.
23.	李金鹏, 王摇瑞, 白人骁. 来氟米特和甲氨蝶呤治疗类风湿关节炎疗效及安全性的荟萃分析. 现代中西医结合杂志, 2011, 2(6): 673-675.
24.	朱湘竹, 周兴军, 陆艾芹, 等. 来氟米特治疗类风湿性关节炎疗效的Meta分析. 现代预防医学2007, 34(11): 2011-2014.

1. 1 Barlett RR, Anagnostopulos H, Zielinski T, et al . Effects of leflunomide on immune responses and models of inflammation. Springer Semin Immunopathal , 1993, 14(4): 381-394.
2. Mldenovic V, Domljan Z, Rozman B, et al . Safety and effectiveness of leflunomide in the treatment of patients with rheumatoidarthritis. Arthritis Rheumat , 1995, 38(11): 1596-1603.
3. Smolen JS, Kalden JR, Scott DL, et al . Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoidarthritis: a double-blind, randomised, multicentre trial. Lancet , 1999, 353(9149): 259-266.
4. Felson DT, Anderson JJ, Boers M, et al . American college of rheumatology preliminary definition of improvement in rheumatoid arthrit is. Arthritis Rheumat , 1995, 38(6): 727-735.
5. 孙凌云, 金欧, 王红. 来氟米特治疗类风湿关节炎的疗效评价. 南京大学学报(自然科学), 2002, 38(5): 632-635.
6. Jadad AR, Moore RA, Corral D, Assessing the quality of the reports of randomized clinical trials: is blinding necessary? control clin trials , 1996, 17(1): 1-12.
7. 吕随峰, 肖飞, 何培根, 等. 爱若华治疗类风湿性关节炎的疗效及其安全性. 临床内科杂志, 2000, 11(6): 375-376.
8. 李向培, 厉小梅, 汪国生, 等. 来氟米特治疗类风湿性关节炎的临床研究. 中国临床药理学与治疗学, 200l, 6 (2): 142-144.
9. 张玲玲, 丁长海, 梁朝朝, 等. 来氟米特治疗类风湿关节炎随机双盲平行对照临床试验. 中国临床药理学杂志, 2005, 9, (97): 341-343.
10. Hu Y, Tu S, Liu P. A randomized, controlled, single-blind trial of leflunomide in the treatment of rheumatoid arthritis. J Tongji Med Univ , 2001, 21(1): 72-74.
11. 钟清, 甘华, 陈恩静, 等. 来氟米特治疗类风湿性关节炎的临床疗效评价. 重庆医科大学学报, 2003, 28 (4): 503-505, 524.
12. 帅宗文, 刘爽, 孙桂华, 等. 来氟米特治疗类风湿性关节炎的Ⅱ期临床试验. 安徽医科大学学报, 2002, 37 (1): 41-43.
13. 姜林锑, 於强, 梅振武. 来氟米特治疗类风湿性关节炎的疗效评价. 中国临床医学, 2000, 7 (4): 413-415.
14. 马骥良. 来氟米特和甲氨喋呤治疗活动性类风湿关节炎的对比观察. 北京医学, 2000, 22 (6): 342-345.
15. Strand V, Cohen S, Schiff M, et al . Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch Intern Med , 1999, 159 (21): 2542-2550.
16. Fiehn C, Jacki S, Heilig B, et al . Eight versus 16-week re-evaluation period in rheumatoid arthritis patients treated with leflunomide or methotrexate accompanied by moderate dose prednisone. Rheumatol Int , 2007, 8(27): 975–979.
17. Bao C, Chen S, Gu Y, et al . Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial. Chin Med J (Engl) , 2003, 116(8): 1228-1234.
18. Emery P, Breedveld FC, Lemmel EM, et al . A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology , 2000, 39: 655-665.
19. Cohen S, Cannon GW, Schiff M, et al . Two-year, blinded, randomized, controlled trail of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Arthritis Rheum , 2001, 44(9): 1984-1992.
20. Ishaq M, Muhammad JS, Hameed K, et al . Leflunomide or methotrexate? Comparison of clinical efficacy and safety in low socio-economic rheumatoid arthritis patients. Mod Rheumatol , 2011, 1(7): 566-589.
21. Peter T, George W, Andreas M, et al . Clinical improvement as peflected in measures of function and health-related quality of life following treatment with leflunomide compare wirh methotrexate in patients with rheumatoid arthritis. Arthritis & Rheumatism , 2000, 3(43): 506–514.
22. Katayama K, Matsuno T. Long-term efficacy of leflunomide on disease activity and inhibition of joint damage: retrospective comparison with methotrexate for Japanese rheumatoid arthritis patients. Mod Rheumatol , 2009, 6(19): 513–521.
23. 李金鹏, 王摇瑞, 白人骁. 来氟米特和甲氨蝶呤治疗类风湿关节炎疗效及安全性的荟萃分析. 现代中西医结合杂志, 2011, 2(6): 673-675.
24. 朱湘竹, 周兴军, 陆艾芹, 等. 来氟米特治疗类风湿性关节炎疗效的Meta分析. 现代预防医学2007, 34(11): 2011-2014.

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Efficacy and Safety of Leflunomide and Methotrexate in Treating Rheumatoid Arthritis: A Meta-analysis

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