Monitoring Epstein-Barr Virus (EBV) Load in Rheumatoid Arthritis Patients Treated With New Immunosuppressive Drugs

Overview

PBMNC DNA is considered a limit above which patients will develop EBV associated post transplant lymphoproliferative disorder. we showed that methotrexate tended to decrease EBV load over time, but this did not reach significance and that TNFa inhibitors did not significantly modify EBV load over time. Our objective is to monitor Epstein Barr Virus load over time in patients with Rheumatoid arthritis under Orencia\* (abatacept) or RoActemra\* (tocilizumab), to detect possible immunosuppression associated EBV dysregulation, as seen in post transplant lymphoproliferative disease.

Current treatment of RA routinely includes potentially immunosuppressive medications like methotrexate and TNFa inhibitors. New immunosuppressive drugs are at disposal, Orencia\* (abatacept) which is a T cell co-stimulation modulator (CTLA4Ig) and RoActemra\* (tocilizumab), an antibody against IL6 receptor. In solid organ transplant recipients under immunosuppressants, emergence of lymphoma can be predicted by monitoring EBV load in peripheral blood mononuclear cells (PBMNCs). EBV load above 1000 copies per 500 ng PBMNC DNA is considered a limit above which patients will develop EBV associated post transplant lymphoproliferative disorder, a condition characterized by polyclonal EBV positive B lymphocyte proliferation which can evolve into EBV positive B cell lymphoma . In a first study, we showed that Rheumatoid arthritis patients have 10 fold systemic EBV overload, very similar to that observed in healthy organ transplant recipients. More recently, we showed that methotrexate tended to decrease EBV load over time, but this did not reach significance and that TNFa inhibitors did not significantly modify EBV load over time. Our objective is to monitor Epstein Barr Virus load over time in patients with Rheumatoid arthritis under Orencia\* (abatacept) or RoActemra\* (tocilizumab), to detect possible immunosuppression associated EBV dysregulation, as seen in post transplant lymphoproliferative disease.