Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage

Objective
The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship.

Methods
We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method.

Results
In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE− patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE− patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4− patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4− patients. Significance was confirmed by multiple regression using log-transformed scores.

Conclusion
Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA.