Methotrexate for ankylosing spondylitis

  • Review
  • Intervention

Authors

  • Junmin Chen,

    Corresponding author
    1. The First Affiliated Hospital of Fujian Medical University, Department of Hematology and Rheumatology, Fuzhou, Fujian Province, China
    • Junmin Chen, Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, 350005, China. drjunminchen@hotmail.com.

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  • Chao Liu,

    1. The First Hosptal of Hebei Medical University, Shijiazhuang, Hebei Province, China
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  • Junfang Lin

    1. The First Affiliated Hospital of Fujian Medical University, Department of Hematology and Rheumatology, Fuzhou, Fujian Province, China
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Abstract

Background

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterised by sacroiliitis and spondylitis. Generally, treatment is limited to the alleviation of symptoms using non-steroidal anti-inflammatory drugs (NSAIDs). Recently, disease-modifying antirheumatic drugs (DMARDs) have been used for patients for whom NSAIDs do not work. Methotrexate (MTX), a widely used DMARD, is effective for rheumatoid arthritis (RA), and so might work for AS too.

Objectives

To evaluate the efficacy and toxicity of MTX for treating AS.

Search methods

We conducted searches in any language in: CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 20, 2005); EMBASE (1980 to November 20, 2005); CINAHL (1982 to November 20, 2005), and the reference sections of retrieved articles.

Selection criteria

Randomised and quasi-randomised trials examining the efficacy of MTX versus placebo, other medication, or no medication, for AS.

Data collection and analysis

Two reviewers independently assessed unblinded trial reports for inclusion, assessed methodological quality and entered trial data into RevMan 4.2 using the double-entry facility. Disagreements were resolved by a third reviewer. In the absence of significant heterogeneity, results for continuous data were combined using weighted mean difference or standardised mean difference. Relative risk was used for dichotomous data.

Main 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. Only the response rate in one trial showed a statistically significant benefit of 36% in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was 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. 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 is questionable. No serious side effects were reported in these trials.

Authors' conclusions

There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality randomised controlled trials of longer durations and with larger sample sizes are needed to clarify the effect(s) of MTX on AS.

Plain language summary

Methotrexate for ankylosing spondylitis

This summary of a Cochrane review presents what we know from research about the effect of methotrexate for ankylosing spondylitis. The review shows that:

There is silver level evidence (www.cochranemsk.org) that for people with ankylosing spondylitis, methotrexate may not improve overall disease activity, physical function, overall pain, pain, tenderness and swelling in the ligaments of the joints, movement of the spine, stiffness or overall well being. It may not cause serious side effects. But there is not enough evidence to be certain of the benefits and harms of methotrexate for ankylosing spondylitis and more research is needed.

What is ankylosing spondylitis and what drugs are used to treat it?
Ankylosing spondylitis (AS) is a type of arthritis, usually in the joints and ligaments of the spine. It may also affect the shoulders, hips, or other joints. Pain and stiffness occurs and limits movement in the back and in other joints that are affected.

Non steroidal anti-inflammatory drugs (NSAIDs) are usually used to stop the pain and stiffness. When people do not do well with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate, are sometimes prescribed. It is not known whether methotrexate controls pain and stiffness in AS, slows the progress of AS, or can stop joint damage.

What are the results of this review?
Benefits of methotrexate
In people with ankylosing spondylitis, at 6 to 12 months, methotrexate

may not improve overall disease activity, physical function, overall pain, pain, tenderness or swelling in the ligaments of the joints, movement of the spine, stiffness and overall well being. But there is not enough evidence to be certain.

Damage to the spine as seen on x-ray was not measured and therefore it is not known whether methotrexate slows damage.

Harms of methotrexate
In people with ankylosing spondylitis, at 6 to 12 months, methotrexate may not cause serious side effects. But there is not enough evidence to be certain. Side effects may include nausea, stomach pain, vomiting, mild diarrhea, mild headaches, mouth sores, changes in liver function, hair loss or mild infections.

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