HLA-DRB1 genes, rheumatoid factor, and elevated C-reactive protein: Independent risk factors of radiographic progression in early rheumatoid arthritis

Objective. To evaluate the prognostic value of HLA-DRB1 antigens, rheumatoi d factor (RF), and C-reactive protein (CRP) with the radiographic outcome o f rheumatoid arthritis (RA). Methods. In total, 139 patients with early RA (< 2 years) were followed up. At the end of 3 year treatment with disease modifying antirheumatic drugs (DMARD) HLA genotyping and external radiographic scoring were performed. Th e time up to the first development of erosive disease [Ratingen radiographi c score (RS) > 0, > 5, > 10] was compared by methods of survival analysis. Results. At 4 years' disease duration, DRB1*04 or DRB1*01 positive patients had RS > 0 or > 10 (73% and 27%, respectively) significantly more frequent ly than DRB1*04 or DRB1*01 negative patients (37% and 7%, respectively). Ne arly independently of the genetic predisposition, RF and elevated CRP at th e start of DMARD treatment were predictive for erosive RA at 4 years. Eleva ted CRP (greater than or equal to 15 mg/l) increased the probability of ero sive RA in DRB1*04 or DRB1*01 positive patients from 64.0% (in patients wit h CRP < 15 mg/l) to 83.9%, and in DRB1*04 and DRB1*01 negative patients fro m 18.8% to 70.1%. The corresponding figures for RF+ and RF- patients were 5 8.2% and 82.5% in HLA predisposed patients and 23.5% and 60.2% in those who were negative for DRB1*04 and DRB1*01. The probability of a RS > 10 was 40 .9% for HLA predisposed patients with elevated CRP. In contrast, no case wi th RS > 10 was found in 43 patients who had neither of these 2, risk factor s. Conclusion. Our findings support that HLA predisposition plays an important role with regard to radiographic progression. However, this effect is modi fied by RF serum concentration and disease activity.