Background/Purpose Autoantibodies and other biomarkers of rheumatoid arthritis (RA) that may be detected years before disease onset in a subset of investigated individuals could be affected by exposures such as smoking. Changes in biomarker levels from the pre-clinical phase to early RA may reflect mechanisms that determine the disease phenotype. Cartilage oligomeric matrix protein (COMP) is a marker of cartilage turnover that has been shown to predict progression of joint damage in RA. Our purpose was to investigate the relation between COMP and smoking, as well as changes in COMP from the pre-clinical phase to early RA, and how these relate to early disease activity.

Methods Between 1991 and 1996, 30 447 subjects from a defined catchment area were included in a health survey. From this population, individuals who developed RA after inclusion were identified by linking the health survey database to a community based RA register and local and national patient administrative databases. In a structured review of the medical records, patients were classified according to the 1987 ACR criteria for RA. One control for each validated case, matched for sex, year of birth and year of screening, who was alive and free of  RA when the index person was diagnosed with RA, was selected from the health survey database. Furthermore, the identified sample of incident cases of RA was linked to an inception cohort of early RA patients (symptom duration <12 months) from the same area. Serum COMP in pre-RA cases and controls, as well as in patients with early RA, was measured with a sandwich ELISA (AnaMar).

Results Serum was available from 167 individuals (131 women, mean age at screening 63 years) who were diagnosed with RA after inclusion in the health survey (a median of 5 years later (range 1–13)). COMP levels were significantly lower among current smokers compared to non-smokers in pre-RA cases (mean 10.1 vs. 11.5 U/L; p=0.009) as well as in controls (mean 10.7 vs 11.9 U/L; p=0.046). Fifty-seven cases (44 women) were also included in the early RA cohort after a median of 4.9 years (interquartile range 3.6-6.7). At inclusion, their mean age was 65 years, 56 % were anti-CCP positive and the mean DAS28 was 4.6 (SD 1.1). COMP levels increased significantly from the pre-RA sample to inclusion in the early RA cohort (mean change 1.6 U/L (SD 4.2); p=0.006).  An increase in COMP tended to be associated with higher DAS28 at inclusion in the early RA cohort (β 0.09; 95 % confidence interval (CI) -0.01 to 0.18; adjusted for age, sex and baseline COMP). This association was observed in particular among smokers at baseline (n=22) (adjusted β 0.22; 95 % CI 0.04 to 0.39) and to a lesser extent in non-smokers (n=35) (adjusted β 0.06; 95 % CI -0.07 to 0.19).

Conclusion COMP levels were lower in smokers among pre-RA cases as well as in controls who did not develop RA. Increasing COMP in the pre-clinical phase of RA appeared to be associated with a severe RA phenotype, in particular among smokers. The relation between early changes in cartilage turnover and long term outcomes in RA should be further studied.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increasing-cartilage-turnover-in-smokers-developing-rheumatoid-arthritis-is-associated-with-high-disease-activity-in-early-disease/