A Systematic Review of Methotrexate for Ankylosing Spondylitis_Chinese Journal of Evidence-Based Medicine

Authors：

LIN Junfang ¹ ,  CHEN Junmin ¹ , LIU Chao ²

1. The First Affiliated Hospital of Fujian Medical University, Fujian 350005, China; 2.The First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050031, China;

Corresponding author：

CHEN Junmin, Email: drchen_cn@yahoo.com.cn

Keywords：

Methotrexate; Ankylosing spondylitis; Systematic review

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Objective 　To evaluate the efficacy and toxicity of methotrexate (MTX) in the treatment of ankylosing spondylitis (AS).
Methods 　Randomized controlled trials (RCTs) were identified from CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 2005); EMBASE (1980 to November 2005); CINAHL (1982 to November 2005). The quality of included trials was evaluated. Data were extracted by two reviewers independently using a specially designed extraction form. The Cochrane Collaboration’s RevMan 4.2 software was used for data analysis.
Results 　Three trials involving 116 patients were included. One 12-month trial compared naproxen plus MTX with naproxen alone. Two 24-week trials compared different doses of MTX with placebo. No statistically significant differences were found for the primary outcome measures of physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs and patient and physician global assessment. The response rate in one trial showed statistically significant benefits of 36% in the MTX group compared with the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was a composite index including assessment of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. However, no single outcome showed a statistically significant difference between the MTX and placebo groups when endpoint results were compared. Therefore, this benefit of MTX was questionable. No serious side effects were reported in these studies.
Conclusions 　There is no enough evidence to show any benefit of MTX in the treatment of AS. High quality randomized controlled trials of longer duration and with larger sample size are needed to clarify the effect of MTX on AS.

Citation： LIN Junfang,CHEN Junmin,LIU Chao. A Systematic Review of Methotrexate for Ankylosing Spondylitis. Chinese Journal of Evidence-Based Medicine, 2007, 07(4): 260-266. doi: Copy

1.	American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis & Rheumatism, 2002, 46(76): 328-346.
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3.	Suarez-Almazor ME, Belseck E, Shea B, et al. Methotrexate for treating rheumatoid arthritis. In: The Cochrane Library, 2, 2003. Oxford: Update Software. 10.1002/14651858.CD000957.
4.	Olivieri I, van Tubergen A, Salvarani C, et al. Seronegative spondyloarthritides. Best Practice & Research Clinical Rheumatology, 2002, 16(92): 723-739.
5.	van der Heijde D, van der Linden S, Ballamy N, et al. Which domains should be included in a core set for endpoints in ankylosing spondylitis? Introduction to the ankylosing spondylitis module of OMERACT IV. The Journal of Rheumatology, 1999, 26(76): 495-497.
6.	van der Heijde D, Braun J, McGonagle D, et al. Treatment trials in ankylosing spondylitis: current and future considerations. Annals of the Rheumatic Diseases, 2002, 61(Suppl III):iii24-iii32.
7.	Altan L, Bingol U, Karakoc Y, et al. Clinical investigation of methotrexate in the treatment of ankylosing spondylitis. Scandinavian Journal of Rheumatology, 2001, 30(5): 255-259.
8.	Roychowdhury B, Bintley-Bagot S, Bulgen DY, et al. Is methotrexate effective in ankylosing spondylitis?. Rheumatology (Oxford), 2002, 41( ): 1330-1332.
9.	Gonzalez-Lopez, Garcia-Gonzalez A, Vazquez-Del-Mercado M, et al. Efficacy of methotrexate in ankylosing spondylitis: A randomized, double blind, placebo controlled trial. The Journal of Rheumatology, 2004, 31(8): 1568-1574.
10.	Xie RL, Li XH, Kang XT. Methotrexate in conjunction with meloxicam for treating ankylosing spondylitis: a clinical observation of the efficacy and safety. Academic Journal of the First Medical College of PLA, 2003, 23(5): 460-462.
11.	Anderson JJ, Baron G, van der Heijde D, et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis & Rheumatism, 2001, 44(8): 1876-1886.
12.	Brandt J, Listing J, Sieper J, et al. Development and preselection of criteria for short term improvement after anti-TNFa treatment in ankylosing spondylitis. Annal of Rheumatic Disseases, 2004, 63(129): 1438-1444.
13.	Biasi D, Carletto A, Caramaschi P, et al. Efficacy of methotrexate in the treatment of ankylosing spondylitis: a three-year open study. Clinical Rheumatology, 2000, 19(64): 114-117.
14.	Clavaguera MT, Juanola X, Narvaez FJ. Methotrexate in the treatment of ankylosing spondylitis. British Journal of Rheumatology, 1998, 37(Supplement 1): 45.
15.	Creemers MC, Franssen MJ, van de Putte LB, et al. Methotrexate in severe ankylosing spondylitis: an open study. Journal of Rheumatology, 1995, 22(6): 1104-1107.
16.	Handler RP. Favourable results using methotrexate in the treatment of patients with ankylosing spondylitis. Arthritis & Rheumatism 1989, 32: 234.
17.	Kirnap M, Demir H, Sigan YT, et al. Efficacy and side effects of low dose methotrexate treatment in the patients with ankylosing spondylitis. Journal of Rheumatology, 2000, 27(Suppl 59): 57.
18.	Ostendorf B, Specker C, Schneider M. Methotrexate lacks efficacy in the treatment of severe ankylosing spondylitis compared with rheumatoid and psoriatic arthritis. Journal of Clinical Rheumatology 1998, 4(25): 129-136.
19.	Sampaio-Barros PD, Costallat LT, Bertolo MB, et al. Methotrexate in the treatment of ankylosing spondylitis. Scandinavian Journal of Rheumatology, 2000, 29(36): 160-162.

1. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis & Rheumatism, 2002, 46(76): 328-346.
2. Dougados M, Revel M, Khan MA. Spondyloarthropathy treatment: progress in medical therapy. Bailliere’s clinical rheumatology, 1998, 12( ): 717-736.
3. Suarez-Almazor ME, Belseck E, Shea B, et al. Methotrexate for treating rheumatoid arthritis. In: The Cochrane Library, 2, 2003. Oxford: Update Software. 10.1002/14651858.CD000957.
4. Olivieri I, van Tubergen A, Salvarani C, et al. Seronegative spondyloarthritides. Best Practice & Research Clinical Rheumatology, 2002, 16(92): 723-739.
5. van der Heijde D, van der Linden S, Ballamy N, et al. Which domains should be included in a core set for endpoints in ankylosing spondylitis? Introduction to the ankylosing spondylitis module of OMERACT IV. The Journal of Rheumatology, 1999, 26(76): 495-497.
6. van der Heijde D, Braun J, McGonagle D, et al. Treatment trials in ankylosing spondylitis: current and future considerations. Annals of the Rheumatic Diseases, 2002, 61(Suppl III):iii24-iii32.
7. Altan L, Bingol U, Karakoc Y, et al. Clinical investigation of methotrexate in the treatment of ankylosing spondylitis. Scandinavian Journal of Rheumatology, 2001, 30(5): 255-259.
8. Roychowdhury B, Bintley-Bagot S, Bulgen DY, et al. Is methotrexate effective in ankylosing spondylitis?. Rheumatology (Oxford), 2002, 41( ): 1330-1332.
9. Gonzalez-Lopez, Garcia-Gonzalez A, Vazquez-Del-Mercado M, et al. Efficacy of methotrexate in ankylosing spondylitis: A randomized, double blind, placebo controlled trial. The Journal of Rheumatology, 2004, 31(8): 1568-1574.
10. Xie RL, Li XH, Kang XT. Methotrexate in conjunction with meloxicam for treating ankylosing spondylitis: a clinical observation of the efficacy and safety. Academic Journal of the First Medical College of PLA, 2003, 23(5): 460-462.
11. Anderson JJ, Baron G, van der Heijde D, et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis & Rheumatism, 2001, 44(8): 1876-1886.
12. Brandt J, Listing J, Sieper J, et al. Development and preselection of criteria for short term improvement after anti-TNFa treatment in ankylosing spondylitis. Annal of Rheumatic Disseases, 2004, 63(129): 1438-1444.
13. Biasi D, Carletto A, Caramaschi P, et al. Efficacy of methotrexate in the treatment of ankylosing spondylitis: a three-year open study. Clinical Rheumatology, 2000, 19(64): 114-117.
14. Clavaguera MT, Juanola X, Narvaez FJ. Methotrexate in the treatment of ankylosing spondylitis. British Journal of Rheumatology, 1998, 37(Supplement 1): 45.
15. Creemers MC, Franssen MJ, van de Putte LB, et al. Methotrexate in severe ankylosing spondylitis: an open study. Journal of Rheumatology, 1995, 22(6): 1104-1107.
16. Handler RP. Favourable results using methotrexate in the treatment of patients with ankylosing spondylitis. Arthritis & Rheumatism 1989, 32: 234.
17. Kirnap M, Demir H, Sigan YT, et al. Efficacy and side effects of low dose methotrexate treatment in the patients with ankylosing spondylitis. Journal of Rheumatology, 2000, 27(Suppl 59): 57.
18. Ostendorf B, Specker C, Schneider M. Methotrexate lacks efficacy in the treatment of severe ankylosing spondylitis compared with rheumatoid and psoriatic arthritis. Journal of Clinical Rheumatology 1998, 4(25): 129-136.
19. Sampaio-Barros PD, Costallat LT, Bertolo MB, et al. Methotrexate in the treatment of ankylosing spondylitis. Scandinavian Journal of Rheumatology, 2000, 29(36): 160-162.

Chinese Journal of Evidence-Based Medicine

A Systematic Review of Methotrexate for Ankylosing Spondylitis

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