Long-term treatment with methotrexate or tumor necrosis factor α inhibitors does not increase Epstein-Barr virus load in patients with rheumatoid arthritis

Objective. We previously demonstrated that patients with rheumatoid arthritis (RA) have a 10-fold systemic Epstein-Barr virus (EBV) overload, very similar to that observed in healthy organ transplant recipients. Our objective was to monitor EBV. load over time in patients with RA receiving methotrexate, infliximab, or etanercept to detect possible immunosuppression-associated EBV dysregulation, as described in posttransplant lymphoproliferative disease. Methods. The EBV load in the peripheral blood mononuclear cells (PBMCs) from 19 patients receiving methotrexate, 68 patients receiving infliximab, and 48 patients receiving etanercept was monitored for durations ranging from 6 months to 5 years using a real-time polymerase chain reaction assay previously developed for that purpose. The effect of treatment duration on EBV load and the link between the Disease Activity Score in 28 joints and EBV load were analyzed by generalized estimating equations. Results. Methotrexate tended to decrease EBV load over time, but this did not reach significance. Tumor necrosis factor a (TNF alpha) inhibitors did not significantly modify EBV load over time. Finally, high disease activity was significantly associated with high EBV load. Conclusion. Long-term usage of methotrexate or TNFa inhibitors in patients with RA does not significantly influence EBV load in PBMCs.