title: Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study.
abstract: BACKGROUND
  Epstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas. Immunosuppressive drugs used to treat RA (conventional disease modifying drugs cDMARDs or biologics bDMARDs) could enhance the risk of developing LPD in RA patients. We have previously shown that long term treatment with Methotrexate and/or TNF alpha antagonists does not increase EBV load in RA. Our objective was to monitor the Epstein-Barr Virus load in RA patients treated with Abatacept (CTLA4 Ig), a T cell coactivation inhibitor, and Tocilizumab, an anti IL6 receptor antibody.
  
  
  METHODS
  EBV load in the peripheral blood mononuclear cells (PBMCs) of 55 patients under Abatacept (in 34% associated with Methotrexate) and 35 patients under Tocilizumab (in 37% associated with Methotrexate) was monitored for durations ranging from 6 months to 3 years by real time PCR. The influences of treatment duration and disease activity score 28 (DAS28) index on EBV load were analyzed.
  
  
  RESULTS
  Abatacept did not significantly modify EBV load over time. Tocilizumab significantly diminished EBV load over time. No patient (of 90) developed EBV associated lymphoma.
  
  
  CONCLUSIONS
  Long term treatment with Abatacept or Tocilizumab does not increase EBV load in the PBMNCs of patients with RA.
authors.affiliation: Rheumatology 1 or 2, IML, AP-HM, 270 Boulevard de Sainte Marguerite, Marseilles, France.|INSERM UMRs 1097, Aix-Marseille University, 163 Avenue de Luminy, Marseilles, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Balandraud
authors.affiliation: CESPA, Centre d'épidémiologie et de santé publique des armées, Marseilles, France.|Aix-Marseille University, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseilles, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Texier
authors.affiliation: Rheumatology 1 or 2, IML, AP-HM, 270 Boulevard de Sainte Marguerite, Marseilles, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Massy
authors.affiliation: Rheumatology 1 or 2, IML, AP-HM, 270 Boulevard de Sainte Marguerite, Marseilles, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Muis-Pistor
authors.affiliation: INSERM UMRs 1097, Aix-Marseille University, 163 Avenue de Luminy, Marseilles, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Martin
authors.affiliation: INSERM UMRs 1097, Aix-Marseille University, 163 Avenue de Luminy, Marseilles, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Auger
authors.affiliation: Rheumatology 1 or 2, IML, AP-HM, 270 Boulevard de Sainte Marguerite, Marseilles, France.
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Guzian
authors.affiliation: Rheumatology 1 or 2, IML, AP-HM, 270 Boulevard de Sainte Marguerite, Marseilles, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Guis
authors.affiliation: Rheumatology 1 or 2, IML, AP-HM, 270 Boulevard de Sainte Marguerite, Marseilles, France.
authors.forename: Thao
authors.initials: T
authors.lastname: Pham
authors.affiliation: Rheumatology 1 or 2, IML, AP-HM, 270 Boulevard de Sainte Marguerite, Marseilles, France.|INSERM UMRs 1097, Aix-Marseille University, 163 Avenue de Luminy, Marseilles, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Roudier
mesh_terms: D000069594:Abatacept / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D019562:Viral Load / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D000069594:Abatacept; C502936:tocilizumab; D008727:Methotrexate