Background The identification of early rheumatoid arthritis (RA) patients that will develop a progressive destructive disease course is important to enable adjusting the treatment strategy to individual patients’ prospects. Previous studies indicated that pyridinoline, a collagen crosslink in cartilage and bone, might be a good marker to predict joint destruction in RA patients. However, up to now no large scale prospective studies on serum pyridinoline levels and severity of joint destruction were performed.
Objectives To investigate the predictive value of pyridinoline serum levels for future joint destruction, both at disease onset and during the disease course.
Methods Early RA patients from the Leiden Early Arthritis Clinic were studied. Patients had hand and feet radiographs taken at baseline and yearly thereafter, that were scored according to the Sharp-van der Heijde Scoring (SHS) method. Baseline and follow-up pyridinoline serum levels were measured by enzyme linked immunoassay (ELISA). Associations between baseline pyridinoline serum levels and radiographic joint destruction over 7 year were analyzed in 437 early RA patients using a multivariate normal regression model, adjusted for age, gender and treatment.
To evaluate the predictive value of serum pyridinoline measurements in more advanced disease, serum of 184 RA patients with mean disease duration of 4 years were studied. Serum levels were associated with the delta SHS over the upcoming year using a multivariate linear regression model, adjusted for age, gender and follow-up duration. Subsequently, both analyses were also adjusted for anti-CCP antibody status and C-reactive protein (CRP).
Results Studying baseline pyridinoline serum levels in 437 patients revealed that the mean SHS over 7 years was 6% higher for every higher nmol/L pyridinoline level at baseline (p=0.001). After adjusting for anti-CCP status the association remained significant (p=0.016). However, after adjusting for baseline CRP level, baseline pyridinoline level was no longer significantly associated with joint destruction over 7 years.
Subsequently follow-up pyridinoline serum levels (n=184 patients) were studied in relation to progression of joint destruction during the next year. For every higher nmol/L pyridinoline level, the progression in SHS was 12% higher (p=0.004). After adjusting for anti-CCP status or CRP level, pyridinoline levels were still significantly associated to joint destruction (p=0.015 and p=0.007, respectively).
Baseline and follow-up pyridinoline levels were correlated (rs=0.251 and p=0.005). CRP levels and pyridinoline levels were also correlated, both at baseline and during follow-up (rs=0.269, p=2.3*10-8 and rs=0.211, p=0.005, respectively).
Conclusions In conclusion, pyridinoline serum levels at disease onset and during the disease course are predictive for the severity of future joint destruction. Although replication is needed, these data suggest that serum pyridinoline level is a relevant biomarker in RA.
Disclosure of Interest A. Krabben: None Declared, R. Knevel: None Declared, T. Huizinga: None Declared, G. Cavet Grant/Research support from: Crescendo Bioscience measured pyrodinoline levels, A. van der Helm-van Mil: None Declared