Risk of Hepatitis B Virus Reactivation Following Treatment with Abatacept: A Retrospective Study of International Pharmacovigilance Databases

Overview

Journal EClinicalMedicine

Specialty General Medicine

Date 2022 Jun 16

PMID 35706497

Authors

Jingjing Wang

Xin Zhang

Xiaozhen Geng

Juanjuan Shi

Xiaoli Jia

Shuangsuo Dang

Wenjun Wang

Affiliations

Soon will be listed here.

Abstract

Background: Abatacept is a selective T-cell costimulation modulator approved for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, and psoriatic arthritis. Reports were recently published on hepatitis B virus reactivation (HBVr) in patients who were treated with abatacept. However, the literature is limited to case reports and series, and no study has investigated the relationship between HBVr and abatacept using extensive population-based databases.

Methods: Using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database, we collected all cases of HBVr between Jan 1, 2006 and June 30, 2021, for abatacept and other drugs. Disproportionality was analysed using the reporting odds ratio (ROR), which was considered significant when the lower limit of the 95% CI was >1. We also conducted a confirmatory analysis in the European pharmacovigilance database, EudraVigilance.

Findings: During the study period, 77,669 adverse cases were reported for abatacept use. There were 2889 reports of HBVr with any drug during this period, of which 55 were reported with abatacept. The ROR for HBVr with abatacept was significantly elevated at 4·80 (95% CI 3·68-6·27). All 55 cases of HBVr with abatacept were reported as serious adverse events. Of them, six individuals were hospitalised and four died. Among 832 reports of HBVr with any drug in EudraVigilance, 43 were reported with abatacept; the ROR was 8·99 (95% CI 6·61-12·23).

Interpretation: We identified a positive signal between abatacept exposure and HBVr. Future prospective studies should further confirm the relationship and provide evidence to develop strategies involving pre-treatment screening, monitoring, and utilisation of antiviral prophylaxis when using abatacept in patients with rheumatic diseases.

Funding: This work was supported by the Fundamental Research Funds for Central Universities (xjh012019063).

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References

Guidotti L, Isogawa M, Chisari F . Host-virus interactions in hepatitis B virus infection. Curr Opin Immunol. 2015; 36:61-6. PMC: 4593767. DOI: 10.1016/j.coi.2015.06.016. View

Liu M, Yu Y, Hu S . A review on applications of abatacept in systemic rheumatic diseases. Int Immunopharmacol. 2021; 96:107612. DOI: 10.1016/j.intimp.2021.107612. View

Goldman S . Limitations and strengths of spontaneous reports data. Clin Ther. 1999; 20 Suppl C:C40-4. DOI: 10.1016/s0149-2918(98)80007-6. View

Guidotti L, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L . Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell. 2015; 161(3):486-500. PMC: 11630812. DOI: 10.1016/j.cell.2015.03.005. View

Talotta R, Atzeni F, Sarzi Puttini P . Reactivation of occult hepatitis B virus infection under treatment with abatacept: a case report. BMC Pharmacol Toxicol. 2016; 17:17. PMC: 4839135. DOI: 10.1186/s40360-016-0060-2. View

Lau G, Yu M, Wong G, Thompson A, Ghazinian H, Hou J . APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int. 2021; 15(5):1031-1048. PMC: 8382940. DOI: 10.1007/s12072-021-10239-x. View

Germanidis G, Hytiroglou P, Zakalka M, Settas L . Reactivation of occult hepatitis B virus infection, following treatment of refractory rheumatoid arthritis with abatacept. J Hepatol. 2011; 56(6):1420-1. DOI: 10.1016/j.jhep.2011.10.011. View

Maxwell L, Singh J . Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009; (4):CD007277. PMC: 6464777. DOI: 10.1002/14651858.CD007277.pub2. View

Hoofnagle J . Reactivation of hepatitis B. Hepatology. 2009; 49(5 Suppl):S156-65. DOI: 10.1002/hep.22945. View

10.

Bluestone J, St Clair E, Turka L . CTLA4Ig: bridging the basic immunology with clinical application. Immunity. 2006; 24(3):233-8. DOI: 10.1016/j.immuni.2006.03.001. View

11.

Walunas T, Bakker C, Bluestone J . CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med. 1996; 183(6):2541-50. PMC: 2192609. DOI: 10.1084/jem.183.6.2541. View

12.

Loomba R, Liang T . Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions. Gastroenterology. 2017; 152(6):1297-1309. PMC: 5501983. DOI: 10.1053/j.gastro.2017.02.009. View

13.

Terrault N, Lok A, McMahon B, Chang K, Hwang J, Jonas M . Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018; 67(4):1560-1599. PMC: 5975958. DOI: 10.1002/hep.29800. View

14.

McMahon B . The natural history of chronic hepatitis B virus infection. Hepatology. 2009; 49(5 Suppl):S45-55. DOI: 10.1002/hep.22898. View

15.

. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017; 67(2):370-398. DOI: 10.1016/j.jhep.2017.03.021. View

16.

Lazarus J, Picchio C, Dillon J, Rockstroh J, Weis N, Buti M . Too many people with viral hepatitis are diagnosed late - with dire consequences. Nat Rev Gastroenterol Hepatol. 2019; 16(8):451-452. DOI: 10.1038/s41575-019-0177-z. View

17.

Ye B, Liu X, Li X, Kong H, Tian L, Chen Y . T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance. Cell Death Dis. 2015; 6:e1694. PMC: 4385920. DOI: 10.1038/cddis.2015.42. View

18.

Stricker B, Tijssen J . Serum sickness-like reactions to cefaclor. J Clin Epidemiol. 1992; 45(10):1177-84. DOI: 10.1016/0895-4356(92)90158-j. View

19.

Cao H, Zhang R, Zhang W . CTLA‑4 interferes with the HBV‑specific T cell immune response (Review). Int J Mol Med. 2018; 42(2):703-712. PMC: 6034931. DOI: 10.3892/ijmm.2018.3688. View

20.

Yang P, Althage A, Chung J, Maier H, Wieland S, Isogawa M . Immune effectors required for hepatitis B virus clearance. Proc Natl Acad Sci U S A. 2010; 107(2):798-802. PMC: 2818933. DOI: 10.1073/pnas.0913498107. View