Tracking levels of key biomarkers reflects disease activity and progression of rheumatoid arthritis

Copenhagen, Denmark, Saturday 13 June 2009: New research has identified biomarkers associated with inflammation and progression in joint erosion in individuals with early rheumatoid arthritis (RA), according to the results of a new study presented today at EULAR 2009, the Annual Congress of the European League Against Rheumatism in Copenhagen, Denmark. The researchers suggest a potential role for these biomarkers in the monitoring of ongoing disease activity through assessing inflammation and joint destruction, two important targets for the treatment of early RA.

Over the 12-month study period, levels of the serological biomarkers sYKL-40 and sMMP3 were consistently associated with three measures of disease activity: MRI (RAMRIS (RA MRI score) synovitis score and RAMRIS bone marrow oedema score) and clinical scores (DAS28*) of inflammation (p<0.05), when the analyses were corrected for age, gender, c-reactive protein (CRP, a marker for inflammation) levels and treatment type. The bone marker sCTX1 and the cartilage marker uCTXII were also shown to be predictors of erosive progression (RAMRIS erosion score; beta 2.42 (95%CI 0.48-4.36)).

Dr Silje Syversen of Diakonhjemmet Hospital, Norway, who led the study, said: “Disease monitoring in RA can be problematic and patients ‘at-risk’ of future irreversible joint destruction can go undetected. Current predictors of joint destruction such as radiographic abnormalities are signs of later-stage disease development. Biomarkers could offer a novel, more sensitive, rapid and reliable approach to disease monitoring and prediction, and importantly could be useful predictors of bone and cartilage damage before such abnormalities have occurred.”

In the study, 84 patients with early RA (disease duration <1 year, mean age 58.4 years, 73.9% females, 55% anti-cyclic citrullinated peptide antibodies (ACPA) positive) were assessed at baseline, 3, 6 and 12 months including clinical examination, conventional radiographs (CR) of the hands and MRI scans of the dominant wrist. RAMRIS score (erosions range 0-150, synovitis range 0-9 and bone marrow oedema range 0-45) was used to evaluate MRI images and the van der Heijde modified Sharp score (vdHSS) was used for for the CRs.

Longitudinal associations between a panel of biomarkers (CRP, sOPG, sRANKL, sCTX1, uCTXII, sYKL40, sCOMP and sMMP3), in serum and urine, were explored by multiple linear mixed model analyses for repeated measures, and multiple linear and logistic regression analyses were used to identify predictors of progression of damage assessed by MRI and CR, respectively.

* DAS28 (Disease Activity Score) is an index used by physicians to measure how active an individual’s RA is. It assesses number of tender and swollen joints (out of a total of 28), the erythrocyte sedimentation rate (ESR, a blood marker of inflammation), and the patient’s ‘global assessment of global health’. A higher score indicates more active disease.

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