Article

Methotrexate for ankylosing spondylitis

Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. .
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2013; 2(2):CD004524. DOI: 10.1002/14651858.CD004524.pub4
Source: PubMed

ABSTRACT 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.
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.

Download full-text

Full-text

Available from: Mirella Veras, Jul 01, 2015
1 Follower
 · 
123 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although TNF-α inhibitors' striking effect on clinical symptoms have revolutionised the treatment of ankylosing spondylitis (AS), no certain influence on the development of spinal ankylosis and joint destruction has been documented. We wished to investigate whether improved treatment has affected the use of hip arthroplasty surgery. Using the Norwegian Arthroplasty Register, we selected hip prosthesis procedures performed in patients with AS in 1988-2010 (n=534), and compared the trend in the number of procedures being performed annually in 1988-2002 versus 2003-2010. Patients with osteoarthritis (OA) (n=95094) were used as a control group. The frequency of hip prosthesis surgery increased significantly in both groups up until 2002. In 2003-2010, although not statistically significant (p=0.087), there was a trend towards a reduced frequency in the AS group when compared with the expected continued increase as was seen among patients with OA. Mean age at surgery increased significantly (p<0.001) from 49.9 years to 56.4 years when comparing patients with AS up until and after 2002. TNF-α inhibitors were introduced to patients with AS in Norway in 2000-2003, and our findings suggest that they may have altered the prognosis by inhibiting or slowing large joint arthritis and thus reducing the need for hip replacement surgery.
    Annals of the rheumatic diseases 11/2013; 73(6). DOI:10.1136/annrheumdis-2013-203963 · 9.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine a concentration-effect curve of adalimumab in rheumatoid arthritis (RA) patients taking into account the effect of methotrexate (MTX) on concentration and effect and to identify a therapeutic range for adalimumab concentrations. In a prospective observational cohort study, 221 consecutive patients with RA were treated with 40 mg adalimumab subcutaneously every other week. The relationship between adalimumab trough level and clinical efficacy after 28 weeks of follow-up was determined in a concentration-effect curve. A receiver-operator characteristics (ROC) curve established a therapeutic cut-off concentration. The effect of MTX on adalimumab trough levels was shown by dividing patients that are and are not concomitantly using MTX in the concentration-effect curve and a concentration table. Clinical efficacy improved with increasing adalimumab concentration and reached a maximum (mean disease activity score in 28 joints improvement of 2) with levels between 5-8 μg/mL. Levels exceeding 8 μg/mL were illustrated to have no additional beneficial effect on disease activity. The ROC curve showed an area under the curve of 0.695 (95% CI 0.626 to 0.764) for European League Against Rheumatism response and adalimumab levels: good responders versus non-responders and moderate responders. A cut-off of 5 μg/mL had a sensitivity of 91% and a specificity of 43%. Adalimumab levels are influenced by concomitant MTX use: patients on adalimumab monotherapy had a median adalimumab level of 4.1 μg/mL (IQR 1.3-7.7), whereas patients concomitantly taking MTX had a median level of 7.4 μg/mL (IQR 5.3-10.6, p<0.001). Adalimumab trough levels in a range of 5-8 μg/mL are sufficient to reach adequate clinical response. These levels are influenced substantially by concomitant MTX use.
    Annals of the rheumatic diseases 12/2013; 74(3). DOI:10.1136/annrheumdis-2013-204172 · 9.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The management of spondyloarthritis is challenging and has changed with the development of new concepts and treatments. To develop practice guidelines for the everyday management of patients with spondyloarthritis (including psoriatic arthritis), by updating previous national and international recommendations, based on a review of recently published data. A task force and a multidisciplinary literature review group were established. The task force identified the issues that remained unresolved. Based on existing recommendations and recent publications, the task force developed practice guidelines, which were revised by the literature review group and graded according to AGREE. Practice guidelines for the management of spondyloarthritis are reported. After a review of the general diagnostic principles, 30 practice guidelines are given: 5 on general principles, 4 on the management strategy, 5 on non-pharmacological treatments, 7 on conventional pharmacological treatments, 6 on biotherapies, and 3 on surgical treatments and follow-up. The updated practice guidelines reported here constitute a global framework that can guide physicians in the everyday management of spondyloarthritis.
    Joint, bone, spine: revue du rhumatisme 01/2014; 81(1). DOI:10.1016/j.jbspin.2013.12.002 · 3.22 Impact Factor