EBV Load Quantification in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis Treated By Abatacept and Tocilizumab

Emmanuel Massy¹, Gaétan Texier², Olivier Muis Pistor³, marielle Martin⁴, Isabelle Auger⁵, jean-Pierre Mattei⁶, Sandrine Guis⁷, Thao Pham^8,9,10, Jean Roudier^11,12,13 and Nathalie Balandraud¹⁴, ¹Rheumatology, Hôpital Sainte Marguerite, marseille, France, ²Centre d'épidémiologie et de santé publique des armées (CESPA) Marseille, marseille, France, ³rheumatology, Hôpital Sainte marguerite, marseille, France, ⁴INSERM UMRS 1097, marseille, France, ⁵Université Aix Marseille II, INSERM UMR1097, Marseille, France, ⁶Rheumatology, Hôpital Sainte Marguerite AP-HM, marseille, France, ⁷Rheumatology 1, CRMBM-CEMEREM 7339, Aix-Marseille Université, AP-HM, CNRS, Marseilles, France, ⁸Rheumatology, Service de rhumatoiogie, Marseille, France, ⁹Rheumatology Department, Sainte Marguerite Hospital, Marseille, France, ¹⁰Rheumatology, APHM, Aix Marseille University, Marseille, France, ¹¹Laboratoire d'Immunogénétique de la polyarthrite rhumatoide, INSERM UMR639, Marseille Cedex 09, France, ¹²Rheumatology 1, Aix Marseille Univ, AP-HM, INSERM, Marseille, France, ¹³Hopital Sainte Marguerite, Marseille, France, ¹⁴Rheumatology 1, AP-HM, INSERM, Marseilles, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: biologic drugs and rheumatoid arthritis (RA), Safety issues

Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: For twenty years, the Epstein-Barr Virus (EBV) has been suspected to contribute to Rheumatoid Arthritis (RA). Immunity against EBV is impaired in RA. RA patients have high titer anti-EBV antibodies [1]. They also have defective EBV specific suppression by T cells. This contributes to a higher risk of developing lymphoma [2]. We hypothesized that, in RA patients, immunosuppressive drugs may enhance the risk to develop LPD (lymphoproliferative disorders), as it is seen in post transplant patients [3]. We have previously shown that Methotrexate and TNF alpha antagonists do not increase EBV load in RA [4,5]. Our purpose is to monitor EBV load in peripheral blood mononuclear cells (PBMC) of RA patients treated with 2 recent bDMARDs: Abatacept (CTLA4 Ig) a T cell activation inhibitor, and Tocilizumab, an anti IL6 receptor antibody to test whether they may enhance EBV load and lymphoma risk.

Methods: Patients :We included 90 patients with RA, 55 treated by abatacept (+/- methotrexate) and 35 treated with tocilizumab (+/-methroexate) followed at the Sainte-Marguerite Hospital Rheumatologic Department Marseille. All patients fullfilled the 1987 American College of Rheumatology criteria. All patients gave informed consent. (Patients Characteristics, Table1) Quantification of viral load – PBMC were separated on Ficoll gradient

– DNA was extracted and quantified by real time PCR [5].

– Quantification of EBV copy number

The Raji EBV positive Burkitt lymphoma cell line, containing 50 copies of EBV per cell, was used as external standard. Real time quantitative PCR (LightCycler, Roche Diagnostics) was performed on 500 ng of DNA. A 214 bp sequence of the Internal Repeat was amplified. Two internal probes were used to improve specificity. Statistics : Generalized estimating equation were used to test whether EBV load is influenced by treatment

Results: Abatacept does not enhance EBV mean load after 3 years of treatment. No lymphoma occured. Tocilizumab was associated with a significant decreased EBV load during time (p = 0.021). None of the patients had a detectable load at 36 months. No lymphoma occured.

Conclusion: Reliable tool to monitor EBV load No obvious change of EBV mean load under treatment with tocilizumab and abatacept Referances 1] Alspaugh M, et al. Journal of Clinical Investigation. 1981 // [2] Tosato G, et al. New England Journal of Medicine 1981 // [3] Baldanti F et al. Journal of Clinical Microbiology, 2000 // [4] Balandraud N, et al. Arthritis and Rheumatism. 2003. [5] Balandraud N et al. Arthritis and Rheumatism. 2007

Disclosure: E. Massy, None; G. Texier, None; O. Muis Pistor, None; M. Martin, None; I. Auger, None; J. P. Mattei, None; S. Guis, None; T. Pham, None; J. Roudier, None; N. Balandraud, Roche Chugai, BMS, 2.

To cite this abstract in AMA style:

Massy E, Texier G, Muis Pistor O, Martin M, Auger I, Mattei JP, Guis S, Pham T, Roudier J, Balandraud N. EBV Load Quantification in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis Treated By Abatacept and Tocilizumab [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/ebv-load-quantification-in-peripheral-blood-mononuclear-cells-of-patients-with-rheumatoid-arthritis-treated-by-abatacept-and-tocilizumab/. Accessed .

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