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: [equation: see text] where Re 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 Re in year 1 ( Re 1) and year 2 ( Re 2), a strong and significant correlation (r = 0.58, p<0.000001) was seen between Re 1 and Re 2.


CONCLUSIONS
Joint destruction is the result of the cumulative burden of inflammation over time, modified by an individual factor Re 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.
Wick
M C
MC
Rheumatology Unit, Department of Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden. marius.wick@ks.se
Lindblad
S
S
Klareskog
L
L
Van Vollenhoven
R F
RF
D000368:Aged; D000704:Analysis of Variance; D018501:Antirheumatic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007596:Joints / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012217:Rheumatoid Factor / Q000097:blood
D018501:Antirheumatic Agents; D012217:Rheumatoid Factor