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• Visualization of structural damage as a surrogate marker of radiographic progression in patients with rheumatoid arthritis
  Alexander Pfeil
  Published on: 22 October 2013

• Published on: 22 October 2013

  Visualization of structural damage as a surrogate marker of radiographic progression in patients with rheumatoid arthritis

  • Alexander Pfeil
  • Other Contributors:
    • Peter Oelzner, Diane M. Renz, Gabriele Lehmann, Gunter Wolf, Joachim B?ttcher

  Dear Editor,

  The article published by Landewe et al. (1) offers novel insights to assess the benefits of new therapeutic strategies in rheumatoid arthritis (RA) which focus more on [the visualization of] structural integrity rather than the inhibition of radiographic progression (1). The authors clearly outline the three major problems of the common superiority study designs:
  I. Differences in progression are...

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  Dear Editor,

  The article published by Landewe et al. (1) offers novel insights to assess the benefits of new therapeutic strategies in rheumatoid arthritis (RA) which focus more on [the visualization of] structural integrity rather than the inhibition of radiographic progression (1). The authors clearly outline the three major problems of the common superiority study designs:
  I. Differences in progression are too small,
  II. Effective Disease Modifying Antirheumatic Drugs used in the control group results in levels of radiographic progression which are too low,
  III. The length of placebo treatment is limited to 3 months preventing an exploration of radiological progression of up to 12 months, which often overestimates the true progression.
  Furthermore, no alternative for radiographs as a gold standard imaging technique exists to quantify radiological progression in Randomized Controlled Trials (RCT). Radiological progression is precisely assessed by established scoring methods using the quantification of erosions and joint space narrowing. Magnetic Resonance Imaging (MRI) as an innovative and sensitive imaging technology has the potential to evaluate RA related joint damage and structural integrity but only for early stages of RA: As pointed out by Landewe et al., we also fully agree that MRI is limited by the differing technical configurations as well as in the quantification of joint space narrowing, especially for long-term observations in RCT.
  As discussed by Landewe et al. one possible solution could be the initiation of non-inferiority trials or the use of enriched study populations to overcome the above mentioned limitations and to achieve the value of significance. Other solutions to detect smaller changes in radiological progression and quantification of structural integrity might include the introduction of computer-assisted techniques for quantification of erosions (2), metacarpal bone mineral density (3) and for measurement of joint space width (4). Computer-based quantifications of metacarpal bone mineral density and joint space narrowing have demonstrated the ability to detect very small change (5, 6). In a head-to- head comparison between the Sharp score and computer-assisted joint space analysis the computer- based technique was able to verify smaller changes in joint space width independent of the severity of RA (7). Additionally, the computer based quantification of metacarpal bone mineral density by digital x-ray radiogrammetry has been able to quantify therapeutic effects based on the PREMIER study and the BesT study (8, 9). In this context, computer-assisted joint space analysis was also able to verify therapy associated changes of joint space width in RA-patients (7). Quantitative data derived from computer-based techniques seems to support and validate established scoring methods. Thus optimal individual therapeutic strategies in daily clinical practice can be designed with less uncertainty, and the quantification of structural integrity in RCT poses an additional benefit. The more widespread use of computer-based methods will help close the gap between visualization of structural damage and inhibition of radiographic progression. Despite remaining issues of complexity, quantitative data derived from computer-based techniques support and validate established scoring methods.

  References

  1. Landewe R, Strand V, van der Heijde D. From inhibition of radiographic progression to maintaining structural integrity: a methodological framework for radiographic progression in rheumatoid arthritis and psoriatic arthritis clinical trials. Ann Rheum Dis 2013;72(7):1113-7.

  2. Langs G, Peloschek P, Bischof H, et al. Model-based erosion spotting and visualization in rheumatoid arthritis. Acad Radiol 2007;14(10):1179-88.

  3. Boettcher J, Pfeil A, Rosholm A, et al. Digital X -ray radiogrammetry combined with semiautomated analysis of joint space widths as a new diagnostic approach in rheumatoid arthritis: a cross- sectional and longitudinal study. Arthritis Rheum 2005;52(12):3850-9.

  4. Pfeil A, Haugeberg G, Hansch A, et al. Value of digital X-ray radiogrammetry in the assessment of inflammatory bone loss in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2011;63(5):666-74.

  5. Hoff M, Haugeberg G, Odegard S, et al. Cortical hand bone loss after 1 year in early rheumatoid arthritis predicts radiographic hand joint damage at 5-year and 10-year follow-up. Ann Rheum Dis 2009;68(3):324-9.

  6. Sharp JT, Angwin J, Boers M, et al. Multiple computer-based methods of measuring joint space width can discriminate between treatment arms in the COBRA trial -- Update of an ongoing OMERACT project. J Rheumatol 2009;36(8):1825-8.

  7. Pfeil A, Oelzner P, Bornholdt K, et al. Joint damage in rheumatoid arthritis: assessment of a new scoring method. Arthritis Res Ther 2013;15(1):R27.

  8. Hoff M, Kvien TK, Kalvesten J, et al. Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study. Ann Rheum Dis 2009;68(7):1171-6.

  9. Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, et al. Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 2009;68(3):330-6.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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