A Predictor of Joint Damage in Ankylosing Spondylitis Identified

[Guest guest]

A Predictor of Joint Damage in Ankylosing Spondylitis Identified

http://www.newswise.com/articles/view/524910/?sc=dwtn

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 inflammatory 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 http://www.rheumatology.org/annual.

Presentation Number: 1225

Serum Matrix Metalloproteinase 3 is an Independent Predictor of Structural

Damage Progression in Patients with Ankylosing Spondylitis (AS)

Walter P. Maksymowych1, Landewé2, Barbara Conner-Spady1, Maxime

Dougados3, Herman Mielants4, Robin A. Poole5, Nandi Wang1, Désirée Van der

Heijde2. 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