WASHINGTON — Elevated expression of matrix metalloproteinase-3 in patients with ankylosing spondylitis may independently predict radiographic disease progression, Dr. Walter P. Maksymowych reported at the annual meeting of the American College of Rheumatology.
Joint and bone damage progression in ankylosing spondylitis becomes evident radiographically over a very long period and further damage can only be predicted from damage already visible on radiographs, making it difficult to diagnose and predict the disease course, said Dr. Maksymowych of the University of Alberta, Edmonton (Arthritis Rheum. 2004;50:2622–32).
This is “perhaps one of the greatest challenges in the field of spondylitis research,” he said. The dependence on radiographic evidence of progression poses major difficulties in “the design of clinical trials of agents that evaluate disease modification.”
Matrix metalloproteinase-3 (MMP3) was the only independent and significant biomarker to predict progression in a panel of nine serologic proteins involved in disease activity and structural damage progression in inflammatory forms of arthritis, as well as osteoclast regulation.
Dr. Maksymowych and his colleagues analyzed the proteins in 100 patients with ankylosing spondylitis in the OASIS (Outcome in Ankylosing Spondylitis International Study) longitudinal cohort that began in 1996 at four centers in the Netherlands, Belgium, and France. The patients had a mean age of 43 years and a mean disease duration of 10.6 years.
The level of MMP3 was the only biomarker that was significantly associated with the progression of structural damage at 2 years, after adjustment for age, sex, disease duration, C-reactive protein levels, and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline. A cutoff level of 68 ng/mL MMP3 in serum and a cutoff score of 10 units on the mSASSS predicted progression at 2 years.
Radiographic progression was 78 times more likely to occur with an MMP3 level of at least 68 ng/mL and an mSASSS of at least 10 units or more than with a lower MMP3 level and a lower damage score. Overall, 15% of the patients fell into that high-risk category. Of those who developed radiographic progression by 2 years, 67% had a high MMP3 level and a high damage score.
“Neither MMP3 nor baseline mSASSS alone are of prognostic value in individual patients. However, the combination of a high MMP3 and a high baseline mSASSS score, as defined by those cutoffs, is of prognostic value in individual patients,” Dr. Maksymowych said. The next step is to test these cutoffs in another cohort of ankylosing spondylitis patients.