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Meta-Analysis
. 2013 Feb 28;2013(2):CD004524.
doi: 10.1002/14651858.CD004524.pub4.

Methotrexate for ankylosing spondylitis

Junmin Chen  1 , Mirella M S Veras, Chao Liu, Junfang Lin
Affiliations
Meta-Analysis

Methotrexate for ankylosing spondylitis

Junmin Chen et al. Cochrane Database Syst Rev. .

Abstract

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. Methotrexate (MTX), a widely used disease-modifying antirheumatic drug (DMARD), is effective for rheumatoid arthritis (RA), and so might work for AS. This is an update of a Cochrane review first published in 2004, and previously updated in 2006.

Objectives: To evaluate the benefits and harms of MTX for treating AS.

Search methods: We searched CENTRAL (The Cochrane Library Issue 6, 2012), MEDLINE (2005 to June 25, 2012), EMBASE (2005 to June 25, 2012), Ovid MEDLINE Scopus, World Health Organization International Clinical Trials Registry Platform and the reference sections of retrieved articles. Trials published in any language were acceptable.

Selection criteria: Randomized controlled trials (RCTs) and quasi-randomized controlled trials (qRCTs) examining the benefits and harms of MTX versus placebo, other medication, or no medication for treatment of AS.

Data collection and analysis: Two review authors independently extracted data and assessed risk of bias. We resolved any disagreements through discussions with a third review author. In the absence of significant heterogeneity, we combined results for continuous data using mean difference or standardized mean difference values. We calculated the risk ratio for dichotomous data.

Main results: We identified three RCTs (no additional new studies), which included 116 participants. Of these three trials, one was a 12-month trial that compared naproxen plus MTX with naproxen alone. Also, there were two 24-week trials that compared different doses of MTX with placebo. We included the outcomes of response, physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs, and patient and physician global assessment. We judged only one trial to be at low risk of bias. Across these three trials, we did not identify any statistically significant differences favoring MTX treatment over no MTX treatment apart from one exception. The response rate in one trial showed a statistically significant absolute benefit of 36% and a number to treat for benefit (NNT) of three in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was based on a composite index that included assessments 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. We did not identify any outcome that showed a statistically significant difference between the MTX treated and no MTX treatment groups when endpoint results were compared. Furthermore, no serious side effects were reported in any of the included trials.

Authors' conclusions: There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality RCTs of larger sample sizes are needed to clarify the effect(s) of MTX on AS.

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Conflict of interest statement

There are no known potential conflicts of interest for this review.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 MTX versus No MTX, Outcome 1 Response in the composite index.
1.2
1.2. Analysis
Comparison 1 MTX versus No MTX, Outcome 2 BASDAI (VAS‐10 cm, 0=no disease activity, 10=severe disease activity) (end point value).
1.3
1.3. Analysis
Comparison 1 MTX versus No MTX, Outcome 3 BASFI (score 0‐10, 0=excellent, 10=poor function) (change from baseline).
1.4
1.4. Analysis
Comparison 1 MTX versus No MTX, Outcome 4 Function index (score 0‐40, 0=the best, 40=the worst) (end point value).
1.5
1.5. Analysis
Comparison 1 MTX versus No MTX, Outcome 5 Pain in the night (VAS‐10 cm, 0=no pain, 10=severe pain) (end point value).
1.6
1.6. Analysis
Comparison 1 MTX versus No MTX, Outcome 6 Pain in the day (VAS‐10 cm, 0=no pain, 10=severe pain) (end point value).
1.7
1.7. Analysis
Comparison 1 MTX versus No MTX, Outcome 7 Spinal pain (VAS 10 cm, 0=no pain, 10=severe) (end point value).
1.8
1.8. Analysis
Comparison 1 MTX versus No MTX, Outcome 8 BASMI (VAS‐10 cm, 0=severely limited spinal mobility, 10=overall normal) (end point value).
1.9
1.9. Analysis
Comparison 1 MTX versus No MTX, Outcome 9 Spondylitis index (score 0‐10, the more severe the disease, the higher the score) (end point value).
1.10
1.10. Analysis
Comparison 1 MTX versus No MTX, Outcome 10 Enthesis index (score 0‐90, the more severe the disease, the higher the score) (end point value).
1.11
1.11. Analysis
Comparison 1 MTX versus No MTX, Outcome 11 Disappearance of peripheral arthritis (event).
1.12
1.12. Analysis
Comparison 1 MTX versus No MTX, Outcome 12 Patient global assessment (different scales, the more severe the disease, the higher the score) (end point value).
1.13
1.13. Analysis
Comparison 1 MTX versus No MTX, Outcome 13 Physician global assessment (different scales, the more severe the disease, the higher the score) (end point value).
1.14
1.14. Analysis
Comparison 1 MTX versus No MTX, Outcome 14 Physical well‐being (VAS 10 cm, 0=feeling very well, 10=very bad).
1.15
1.15. Analysis
Comparison 1 MTX versus No MTX, Outcome 15 Morning stiffness duration (units not specified in trial report, we assumed minutes).
1.16
1.16. Analysis
Comparison 1 MTX versus No MTX, Outcome 16 Severity of morning stiffness (VAS 10 cm, 0=no stiffness, 10=severe).
1.17
1.17. Analysis
Comparison 1 MTX versus No MTX, Outcome 17 Health assessment questionnaire for spondyloarthropathies (HAQ‐S) (0‐3, 0=no difficulty, 3=unable to do).
1.18
1.18. Analysis
Comparison 1 MTX versus No MTX, Outcome 18 CRP (change from baseline) (percentage for Altan, ug/ml for others).
1.19
1.19. Analysis
Comparison 1 MTX versus No MTX, Outcome 19 ESR (percentage change from baseline).
1.20
1.20. Analysis
Comparison 1 MTX versus No MTX, Outcome 20 Side effect.
1.21
1.21. Analysis
Comparison 1 MTX versus No MTX, Outcome 21 Withdrawal for any reason.
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Update of

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