Best Tools to Measure Joint Damage in RA

Mar 28, 2016

Both bone erosion and joint space narrowing are important indicators of physical disability in rheumatoid arthritis (RA), but measuring soft tissue damage not as relevant.

Both bone erosion and joint space narrowing are important indicators of physical disability in patients with rheumatoid arthritis (RA), but measuring soft tissue damage with subluxation (SLUX), which is a consequence of long-term RA, doesn’t seem to be relevant.

Writing in the March 11 issue of the journal RMD Open: Rheumatic & Musculoskeletal Diseases, Ana Maria Gherghe, M.D., of Leiden University Medical Center in the Netherlands, and colleagues found that cartilage loss, measured by joint space narrowing, is important in assessing physical function. But in examining joints separately, erosive damage of the wrist and joint space narrowing of the metacarpophalangeal joints (MCPs) - together - are the best indicators for measuring disability. 

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“These data indicate that the comprehensive assessment of joint damage is needed to reliably reflect disease-related damage,” the authors wrote. “In clinical practice, an aggregated score, such as Sharp van der Heijde, is needed to reliably reflect disease-related damage.”

Using three-year follow-up data from two randomized controlled trials, Rheumatoid Arthritis Prevention of structural Damage (RAPID 1) and RAPID 2, researchers evaluated the effects of bone erosion, cartilage loss associated with joint space narrowing, and soft tissue damage in patients with rheumatoid arthritis. Patients in the RAPID trials were randomized into one of two groups:  certolizumab pegol (200 or 400 mg) with methotrexate or placebo with methotrexate. Researchers included 847 patients from the 52-week RAPID 1 trial and 567 from the 24-week RAPID 2 trial.

Radiographs of patients’ hands and feet were acquired at baseline, weeks 24 and 52. For open label extensions of the trial beginning at week 16, radiographs were obtained at weeks 76, 100 and 148 among patients completing 52 weeks of treatment. Physical function was assessed using Health Assessment Questionnaire (HAQ) and radiographic damage assessments were conducted using the van der Heijde modified Sharp scoring, which allows separate scoring for bone erosions, joint space narrowing, and subluxation.

Researchers found that erosion and joint space narrowing were each more strongly associated with physical functioning as compared to subluxation. In combined models, joint space narrowing was the only type of lesion associated with HAQ when all joints were included. When separate joint groups were analyzed, erosion in the wrist and cartilage loss in the metacarpophalangeal joints (MCPs) were most strongly associated with function.

When all types of radiographic measures were included in a single combined multivariate analysis, only joint space narrowing was associated with physical function. The authors could not identify an independent contribution of SLUX to explain the variation in HAQ score.

“In accordance with other studies, we found ‘real JSN’ to be most contributory to explaining the HAQ score. That does not mean that SLUX (or erosion) is not important; in fact, there was a numerical association between subluxation score and HAQ score that was not statistically significant. It only indicates that the contribution of erosions and SLUX is appropriately captured by JSN. In other words: erosions and SLUX in this cohort rarely occur as the only phenomena, but, usually - if not always - in conjunction with JSN. An alternative explanation could be that erosions and SLUX are rare phenomena in comparison with ‘real’ JSN. That is definitely not true for erosions, which occur as often as ‘real’ JSN, but likely true for SLUX that were indeed rare in these trials. Since SLUX is a known late consequence of long-term RA, and the effects of SLUX are captured by JSN, the inclusion of SLUX in the scoring method for radiographic damage does not seem to be very relevant. However, there is also no indication that SLUX jeopardizes the performance of the modified Sharp score, and it does not make sense to remove SLUX from the current score,” the authors wrote.

Limitations of the study included the high number of statistical tests performed and the sensitivity of methods such as GEE that make use of all data available.



Gherghe AM, Ramiro S, Landewé R, et al. "Association of the different types of radiographic damage with physical function in patients with rheumatoid arthritis: analysis of the RAPID trials." RMD Open. 2016;2:e000219. doi: 10.1136/rmdopen-2015-000219.