Immunogenetic markers and seropositivity predict radiological progression in early rheumatoid arthritis independent of disease activity

Objective. A prospective clinical study of patients with recent onset rheum atoid arthritis (RA) to examine the relationship between inflammatory disea se activity and joint destruction in a 4 year followup, and to evaluate pro gnostic markers for severe joint erosions early in the disease. Methods, Eighty-seven patients with RA according to the American College of Rheumatology criteria and a disease duration < 2 years were followed for a n observation time of 2 to 1 years (mean 3.1 yrs). Variables of clinical an d laboratory disease activity were monitored, and HLA-DRB1 alleles were det ermined. Hand and foot radiographs were taken every 6 months. Results. Multivariate analysis of independent contributions of covariates t o progression of joint destruction resulted in a mixed effect regression mo del with significant influences for the presence of a shared epitope (SE) p ositive DR4 allele (SE+ DR4+; p = 0.007), rheumatoid factor (RF) IgA (p = 0 .01), and sex (p = 0.059), but not for clinical variables or acute phase re actants. The odds ratio to reach a Larsen score above 32 during the observa tion period of 4 years was increased in patients positive for RF IgM (OR 2. 7, p = 0.019), for the shared epitope on a DR4 allele (OR 8.6, p < 0.005), and in patients with erosions already at study entry (OR 11.9, p = 0.001). The highest sensitivity and specificity for the prediction of severe bone d estruction (84% and 79%) were found when the presence of either a SE+ DR4 a llele or of early erosions was used as a prognostic marker (OR 20.4. p<0.00 01). Conclusion, Our results show the pace of joint destruction in RA to be infl uenced by the presence of SE+ DR4 alleles, RF production, and sex and by th e presence of erosive disease at presentation. Those prognostic markers exe rt their influence independently from the inflammatory disease activity.