In an ongoing collaborative prospective study aimed at the identification of prognostic factors for the development of erosive disease and clinical severity of disease in early rheumatoid arthritis (RA) [1], 48 patients were followed for more than 4 years, and 87 patients were seen for 2 years. Significant associations with progressive joint destruction, measured by the Larsen index, were observed after 2 and 4 years for three parameters: 1) the presence of rheumatoid factor IgM; 2) bony erosions present at study entry, and 3) HLA DRB1 markers. Patients who expressed the shared epitope on a DR4 allele had significantly higher Larsen indices after 2 years (0.86 vs 0.12; P = 0.0015) and after 4 years (1.22 vs 0.53; P = 0.002) of disease duration. Similarly, the presence of the epitope sequence on either DR1 or DR4 also resulted in higher Larsen indices for epitope-positive patients (0.59 vs 0.06; P = 0.006 after 2 years, and 1.0 vs 0.69; P = 0.03 after 4 years). A more severe radiologic outcome after 2 years (Larsen index > 0.7) was detected with a sensitivity of 0.7, 0.61, and 0.58 and a specificity of 0.42, 0.84 and 0.75 using RF IgM, erosiveness at initial presentation, and presence of the shared epitope on a DR4 as prognostic parameters. Most useful, however, was the combination of DR4 positivity and erosiveness at study entry as prognostic indicators of a more severe course of joint destruction (sensitivity 0.68; specificity 0.77).

In summary, seropositivity, early erosiveness, and RA-associated HLA-DRB1 markers are useful prognostic indicators of the progression of joint destruction. Moreover, this influence is sustained during the first four years of the course of the disease.