Researchers in the Cochrane Collaboration conducted a review about the effect of the drug methotrexate in people with ankylosing spondylitis (AS). They identified three studies, which included 116 participants, that met the inclusion criteria.
The review shows that for people with AS:
- methotrexate probably improves physical function but this may have happened by chance.
- it is uncertain whether methotrexate will help to ease pain, tenderness, and swelling in the ligaments of the joints, movement of the spine, stiffness, or overall well-being because there were not enough participants studied.
- it is uncertain whether methotrexate slows damage to the joints because the studies did not look at an x-ray of the spines of the people with AS.
We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects include stomach problems, mild headaches, mouth sores, changes in liver function, hair loss, or mild infections. Rare complications may include lung problems. It is important to keep medical appointments to catch any serious problems early.
What is AS and what is methotrexate?
AS is a type of arthritis that usually occurs 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.
Methotrexate (MTX) is a disease-modifying antirheumatic drug (DMARD). It is the most commonly used DMARD in people with inflammation in their joints. It works to control inflammation in affected joints to stop the pain and stiffness. MTX is taken once per week and may be administered in pill form or as an injection.
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.
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.
To evaluate the benefits and harms of MTX for treating AS.
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.
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.
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.
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.