Protein predicts damage in ankylosing spondylitis

[Mike Bartolatz]

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A PREDICTOR OF JOINT DAMAGE IN ANKYLOSING SPONDYLITIS IDENTIFIED
WASHINGTON , DC – The protein marker, metalloproteinase 3, now identified as the first significant predictor of joint damage in ankylosing spondylitis, could change patient treatment approaches, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

Ankylosing spondylitis is an i nflammatory arthritis which causes breakdown of bone and cartilage, primarily in the spine and large joints, and can lead to inflammation of the eyes, lungs and heart valves. Disease intensity varies among the some 500,000 Americans with ankylosing spondylitis, and most often starts in men between the ages of 20 and 40. Patients can experience severe joint and back stiffness, even loss of motion and deformity, as life progresses due to complete fusion of spinal bones. While evidence points to the disease’s having a genetic basis, diagnosis is often delayed for many years as patients are thought to have common back problems. This difficulty in diagnosing, and following the disease, makes predicting its course extremely important. However, until recently, only damage already visible on X-ray has proven to be a predictor of further joint damage from ankylosing spondylitis.

An analysis of data collected from an on-going study of ankylosing spondylitis patients across four centers in the Netherlands, Belgium and France since 1996 has changed this. Researchers analyzed patient blood samples for numerous protein biomarkers that indicate cartilage breakdown and are associated with deformities in another related disease, rheumatoid arthritis. Baseline clinical and X-ray data as well as two-year progress data were analyzed and correlated to measurements of proteins important in bone and cartilage metabolism detected in the blood of these 100 patients. Of all the proteins assessed, metalloproteinase 3 proved to be strongly associated with progressive joint and bone damage, particularly in those patients with pre-existing damage visible on X-ray.

“With this biomarker we can now target patients at highest risk for joint damage and in greatest need for effective therapy,” explains Walter P. Maksymowych, MD, Professor of Medicine, University of Alberta, Edmonton, Alberta, Canada, and an investigator in the study. “Being able to predict disease activity and damage in ankylosing spondylitis in patients can lead to more aggressive treatment when the disease is active and more aggressive.”

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see www.rheumatology.org/annual.

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Editor’s Notes: Dr. Maksymowych present this research during a scientific session at the ACR Annual Scientific Meeting from 11:45 am to noon EST on Monday, November 13, 2006 in Ballroom A-C of The Washington Convention Center. He will be available for media questions and briefing at 8:30 am EST on Tuesday, November 14, in the on-site Press Conference Room 209C.


Presentation Number: 1225

Serum Matrix Metalloproteinase 3 is an Independent Predictor of Structural Damage Progression in Patients with Ankylosing Spondylitis (AS)

Walter P. Maksymowych 1, Robert Landewé 2, Barbara Conner-Spady 1, Maxime Dougados 3, Herman Mielants 4, Robin A. Poole 5, Nandi Wang 1, Désirée Van der Heijde 2. 1University of Alberta, Edmonton, AB, Canada; 2University of Maastricht, Maastricht, The Netherlands; 3Hopital Cochin, Paris, France; 4University Hospital, Gent, Belgium; 5Shriners Hospital, Montreal, PQ, Canada

Background. In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in AS. Several serological biomarkers, primarily reflecting cartilage and bone turnover, have been identified as independent predictors in rheumatoid arthritis (RA). Since structural damage impairs function and spinal mobility, it is important to identify prognostic factors for radiographic progression in AS.

Objective. To analyse serological biomarkers as predictors of radiographic progression in AS.

Methods. We measured a panel of serological biomarkers reflecting cartilage turnover and osteoclasis that have been implicated in RA (cartilage oligomeric matrix protein, human cartilage glycoprotein-39 (YKL-40), C2C epitope, C1,2C epitope, 846 epitope, CPII epitope, osteoprotegerin, matrix metalloproteinase 3 (MMP3). All assays were conducted by ELISA. The analysis was performed in an ongoing longitudinal cohort of consecutive AS patients from 4 centres in the Netherlands, Belgium, and France that started in 1996 (OASIS). For this analysis we used baseline clinical and radiographic data, as well as 2-year radiographic progression data. Radiographic progression was scored by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)(range: 0-72) by one observer who was aware of the time order of the X-rays.

Results. Complete data of 100 patients were available for analysis. Of all biomarkers tested, only YKL40 and MMP3

showed weak to moderate correlation with 2-year progression. After adjustment for sex, age, disease duration, and for CRP and baseline mSASSS, MMP3 was the only biomarker that was significantly associated with 2-year progression (st. beta: 0.29, P=0.004). Logistic regression analysis revealed MMP3 (cut-off: 68, OR 9.4 (95%CI: 1.6 to 56) and baseline mSASSS (cut-off: 10 mSASSS units, OR 18.6 (2.5 to 138) as the only independent predictors of 2-year progression (cut-off: 3 mSASSS-units)(model-R2: 0.50). The probability plot shows that MMP3 is primarily contributory in patients with already substantial baseline damage (>10 mSASSS units, corresponding with at least 2 bridging plus 2 non-bridging syndesmophytes) present.

Conclusion. MMP3 is a significant independent predictor of radiographic progression in AS. MMP3 works best as biomarker in AS patients with pre-existing radiographic damage.



Disclosure Block: W.P. Maksymowych, None










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