Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Abatacept/*therapeutic use ; Antibodies, Monoclonal, Humanized/*therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Herpesvirus 4, Human/*physiology ; Immunosuppressive Agents/*therapeutic use; Abatacept/pharmacology ; Adult ; Aged ; Antibodies, Monoclonal, Humanized/pharmacology ; Arthritis, Rheumatoid/pathology ; Arthritis, Rheumatoid/virology ; DNA, Viral/analysis ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/isolation & purification ; Humans ; Immunosuppressive Agents/pharmacology ; Male ; Methotrexate/therapeutic use ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Viral Load/drug effects

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.
Conclusion: Long term treatment with Abatacept or Tocilizumab does not increase EBV load in the PBMNCs of patients with RA.

J Immunother. 2002 Nov-Dec;25(6):455-68. (PMID: 12439343)
Arthritis Rheum. 2006 Mar;54(3):692-701. (PMID: 16508929)
Exp Clin Transplant. 2014 Jun;12(3):212-9. (PMID: 24907721)
J Clin Virol. 2010 Jun;48(2):82-90. (PMID: 20395167)
Ann Rheum Dis. 2006 Dec;65(12 ):1667-9. (PMID: 17105857)
Drugs Today (Barc). 2006 Sep;42(9):559-76. (PMID: 17028666)
Arthritis Rheum. 2006 Dec;54(12 ):3774-81. (PMID: 17133544)
Lancet. 2008 Mar 22;371(9617):987-97. (PMID: 18358926)
Arthritis Rheum. 2007 Jun 15;57(5):762-7. (PMID: 17530675)
Expert Opin Investig Drugs. 2003 Apr;12(4):673-81. (PMID: 12665422)
J Rheumatol. 2013 Jun;40(6):787-97. (PMID: 23588946)
Mod Rheumatol. 2016 Sep;26(5):642-50. (PMID: 26873430)
J Clin Microbiol. 2000 Feb;38(2):613-9. (PMID: 10655355)
Am J Transplant. 2005 Mar;5(3):443-53. (PMID: 15707398)
Curr Opin Rheumatol. 2006 May;18(3):277-81. (PMID: 16582692)
Ann Rheum Dis. 2000 Jul;59(7):533-8. (PMID: 10873963)
Cochrane Database Syst Rev. 2011 Feb 16;(2):CD008794. (PMID: 21328309)
Arthritis Res Ther. 2008;10(2):R45. (PMID: 18433475)
Stat Med. 2004 Mar 30;23(6):859-74; discussion 875-7,879-80. (PMID: 15027075)
Rheumatology (Oxford). 2011 Jan;50(1):222-9. (PMID: 21148156)
Joint Bone Spine. 2016 Jul;83(4):412-5. (PMID: 26725744)
Eur J Cancer. 1996 Sep;32A(10):1753-7. (PMID: 8983286)
Curr Opin Rheumatol. 2004 May;16(3):254-61. (PMID: 15103253)
J Clin Invest. 1984 Jun;73(6):1789-95. (PMID: 6327772)
Clin Microbiol Infect. 2015 Jun;21(6):604.e1-9. (PMID: 25686696)
Arthritis Rheum. 1988 Mar;31(3):315-24. (PMID: 3358796)
N Engl J Med. 2003 Nov 13;349(20):1907-15. (PMID: 14614165)
J Clin Invest. 1981 Apr;67(4):1134-40. (PMID: 6259211)
Blood. 2002 Jun 1;99(11):3909-15. (PMID: 12010788)
Mod Rheumatol. 2017 Jan;27(1):66-71. (PMID: 27166661)
Clin Microbiol Infect. 2014 Sep;20 Suppl 7:109-18. (PMID: 24475976)
Arthritis Rheum. 2006 Sep;54(9):2817-29. (PMID: 16947782)
Arthritis Rheum. 1995 Jan;38(1):38-43. (PMID: 7818569)
N Engl J Med. 1981 Nov 19;305(21):1238-43. (PMID: 6270556)
Arthritis Res Ther. 2006;8 Suppl 2:S5. (PMID: 16899109)
Arthritis Rheum. 2003 May;48(5):1223-8. (PMID: 12746895)
Transpl Int. 2000;13 Suppl 1:S399-401. (PMID: 11112041)
N Engl J Med. 2005 Sep 15;353(11):1114-23. (PMID: 16162882)
J Clin Virol. 2012 Mar;53(3):186-94. (PMID: 22182950)
JAMA. 2012 Sep 5;308(9):898-908. (PMID: 22948700)
Viral Immunol. 2015 Sep;28(7):385-90. (PMID: 26083265)
Rev Med Virol. 2005 May-Jun;15(3):149-56. (PMID: 15546128)
Rheumatology (Oxford). 2016 May;55(5):874-82. (PMID: 26822072)

0 (Antibodies, Monoclonal, Humanized)
0 (DNA, Viral)
0 (Immunosuppressive Agents)
7D0YB67S97 (Abatacept)
I031V2H011 (tocilizumab)
YL5FZ2Y5U1 (Methotrexate)

Date Created: 20170216 Date Completed: 20170828 Latest Revision: 20190208

20231215

PMC5310777

10.1371/journal.pone.0171623

28199343