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SAT0163 Long Term Treatment with Abatacept or Tocilizumab Does Not Increase Epstein-Barr Virus Load in Patients with Rheumatoid Arthritis
  1. E. Massy1,
  2. O. Muis-Pistor1,
  3. M. Martin2,
  4. I. Auger2,
  5. M.-C. Guzian1,
  6. S. Guis1,3,
  7. J. Roudier1,2,
  8. T. Pham4,
  9. N. Balandraud1,2
  1. 1Rheumatology 1, AP-HM, Aix Marseille University
  2. 2UMRs1097, INSERM, Marseilles
  3. 3CRMBM/CEMEREM UMR 7339, Aix Marseille University, Marseille
  4. 4Rheumatology 2, AP-HM, Aix Marseille University, Marseilles, France


Background Epstein-Barr Virus (EBV) is a widely disseminated lymphotrophic herpes virus implicated in a lot of benign and malignant disorders. In transplant patients, EBV load is enhanced because of immunosuppressive drugs (cyclosporine) and in a few cases, it can lead to lymphoproliferative disorders (LPD). An EBV load higher than 500 copies per 500 ng of DNA is a predictive factor of post transplant lymphoma [1,2] Similarly, immunity against EBV is particular in RA patients: the level of antibodies against EBV is higher in RA than in healthy controls [3], RA patients have a defective EBV specific supressor T cell function [4].The risk to develop a lymphoma is higher in RA patients than in controls. We have previously shown that: 1/ EBV load is 10 fold higher in RA patients than in controls [5] and 2/ Methotrexate and TNF alpha antagonists (immunosuppressive drugs used in RA patients) do not increase EBV load in RA [6].

Objectives Here, we monitored EBV load over 3 years in patients with RA treated by 2 more recent biologics, Abatacept (CTLA4 Ig) a T cell activation inhibitor, or Tocilizumab, an anti IL6 receptor antibody.

Methods EBV load in the peripheral blood mononuclear cells (PBMCs) from 55 patients under Abatacept (+/− Methotrexate) and 35 patients under Tocilizumab (+/− Methotrexate) was monitored from 6 months up 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 Neither Abatacept nor Tocilizumab significantly enhanced EBV load over time. None of our patients developed EBV associated lymphoma.

Conclusions Long term usage of Methotrexate with Abatacept or Tocilizumab in patients with RA does not significantly influence EBV load in PBMCs.

  1. Baldanti F et al. High levels of Epstein Barr virus DNA in blood of solid organ transplant recipients and their value in predicting postransplant lymphoproliferative disorders. Journal of Clinical Microbiology 38: 613–619, 2000

  2. Morito M,et al. Quantitative analysis of Epstein Barr virus load by using a real time PCR assay. Journal of Clinical Microbiology 37: 132–136, 1999

  3. Alspaugh M et al. Elevated levels of antibodies to Epstein Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis. Journal of Clinical Investigation 67: 1134–1140, 1981

  4. Tosato G et al. Defective EBV specific suppressor T cell function in rheumatoid arthritis. New England Journal of Medicine 305: 1238–1243, 1981

  5. Balandraud N et al. Epstein-Barr Virus Load in the peripheral blood of patients with Rheumatoid arthritis. accurate quantification using re[2] Kimura H, al time Polymerase chain reaction. Arthritis and Rheumatism 2003;48:1223–1228.

  6. Balandraud N et al. Long-term treatment with methotrexate or tumor necrosis factor alpha inhibitors does not increase epstein-barr virus load in patients with rheumatoid arthritis. Arthritis and Rheumatism 57(5): 762–767, 2007

Acknowledgement This work was supported by AORC AP-HM, INSERM and Chugai.

Disclosure of Interest E. Massy: None declared, O. Muis-Pistor: None declared, M. Martin: None declared, I. Auger: None declared, M.-C. Guzian: None declared, S. Guis: None declared, J. Roudier: None declared, T. Pham: None declared, N. Balandraud Grant/research support from: This work has been partially supported by Chugai group

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