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

Abstract

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:

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) ΔLarsen 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.