title: Long-term treatment with methotrexate or tumor necrosis factor alpha inhibitors does not increase epstein-barr virus load in patients with rheumatoid arthritis.
abstract: 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 alpha (TNFalpha) inhibitors did not significantly modify EBV load over time. Finally, high disease activity was significantly associated with high EBV load.
  
  
  CONCLUSIONS
  Long-term usage of methotrexate or TNFalpha inhibitors in patients with RA does not significantly influence EBV load in PBMCs.
authors.affiliation: INSERM Unité 639, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Balandraud
authors.forename: Sandrine
authors.initials: S
authors.lastname: Guis
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Meynard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Auger
authors.forename: Jean
authors.initials: J
authors.lastname: Roudier
authors.forename: Chantal
authors.initials: C
authors.lastname: Roudier
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D000068800:Etanercept; D005260:Female; D006304:Health Status; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects*; D007074:Immunoglobulin G / Q000009:adverse effects; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept; D008727:Methotrexate