Can gold therapy be used more safely in rheumatoid arthritis? Adverse drug reactions are more likely in patients with nodular disease, independent of HLA-DR3 status

Objective. To investigate whether features associated with severe rheumatoid arthritis (RA) are predictive of adverse drug reactions (ADR) to gold salts, independent of HLA-DR3 status. Methods. A cohort of patients with RA (n = 41) who developed thrombocytopenia (platelets <100 × 10 6/l) or proteinuria (> 1.0 g/24 h) upon treatment with gold sodium thiomalate was identified from patient records and matched for age, sex, and disease duration with 41 RA controls treated with gold without development of ADR. A second group of 161 random RA patients that had received gold therapy for at least as long without development of an ADR was also compared. All patients were typed for HLA-DRB1, and the presence of rheumatoid factor (RF), antinuclear antibodies (ANA), and nodules before initiation of therapy was recorded. Association of clinical or genetic factors with ADR was investigated using the McNemar test and logistic regression analysis. Results. Patients with ADR were more likely to have nodular disease than their matched controls (51.3% vs 25.6%; odds ratio, OR = 3.0, p = 0.02) and more likely to be HLA-DR3 positive (41.2% vs 17.6%; OR = 3.0, p = 0.045). No difference between the groups was found for RF or ANA. Nodular disease was associated with development of ADR independently of HLA-DR3, although a combination of both factors significantly increased the likelihood of an ADR. Conclusion. Our data suggest that nodular disease may be a predictor of gold-induced ADR independent of HLA-DR3.