Relationship between inflammation and joint destruction in early rheumatoid arthritis: a mathematical description

Background: The relationship between inflammation and joint destruction in rheumatoid arthritis ( RA) has not been unequivocally characterised. Joint destruction may result from the cumulative inflammatory burden over time, modified by an individual constant factor. Objective: To test the hypothesis that the relationship between radiological progression and inflammation can mathematically be expressed as: Delta(t-->t+1)(joint dmage) = R . (t) integral(t+1) (inflammation) where R is a factor that varies from person to person. Methods: Clinical data and radiographs of 76 patients with early RA receiving different disease modifying antirheumatic drugs were analysed. Radiographs were quantified using the modified Larsen score and the "X-Ray RheumaCoach'' software. The cumulative inflammatory burden was estimated by the time integrated 28 joint Disease Activity Score (DAS28), calculated as the area under the curve. Results: 76 patients with early RA who started treatment with methotrexate (n = 20), sulfasalazine ( n = 37), or oral gold ( n = 19) monotherapy were evaluated. The mean (SEM) DAS28 decreased from 4.6 (0.1) at baseline to 2.3 ( 0.1) after 2 years. The mean ( SEM) DeltaLarsen score from baseline to year 2 was 10.3 (1.5). Correlation between cumulative inflammation and radiographic change was poor. In contrast, when calculating a person's factor R in year 1 (R1) and year 2 (R2), a strong and significant correlation (r = 0.58, p <0.000001) was seen between R1 and R2. Conclusions: Joint destruction is the result of the cumulative burden of inflammation over time, modified by an individual factor R that remains relatively constant over the first 2 years of observation. The data support a mathematical model that expresses the interrelationship between inflammation and joint destruction