FRI0218 Safety of Non Anti-TNF Biologic Agents in Rheumatic Patients with Past Hepatitis B Virus Infection. A Single-Center Real-Life Study

Abstract

BackgroundThe safety of newer non anti-TNF biologic agents [abatacept (ABA), tocilizumab (TCZ) and rituximab (RTX)] in patients with autoimmune rheumatic diseases and past HBV infection [defined as HBsAg(−), anti-HBc(+), anti-HBs(±)] has not been firmly established.ObjectivesTo assess the safety [reactivation of hepatitis B virus (HBV)] of non anti-TNF biologic agents in patients with serologic evidence of past HBV infection in real-life clinical settings.MethodsRetrospective chart review of patients followed in the Department of Rheumatology of the University Hospital of Crete. Patients who received ABA, TCZ or RTX during the period 2005–2015 and were HBsAg(−), anti-HBc(+), anti-HBs(±) at baseline were identified and reviewed for cases of HBV reactivation (defined as increased ALT accompanied by an increase of serum HBV DNA levels by >1 log10 compared with baseline or a switch in HBV DNA detection from negative to positive). Changes in anti-HBs titers during biologic therapy in patients who were anti-HBs(+) at baseline were also documented.Results83 different cases of non anti-TNF biologic therapy (34 ABA, 26 RTX and 23 TCZ) from 58 patients (56 RA - 2 ANCA-associated vasculitis) were identified. 64 cases (77.1%) were anti-HBc(+) anti-HBs(+) and 19 (22.9%) were anti-HBc(+) anti-HBs(−). Mean (SD) age at disease diagnosis and at non anti-TNF initiation was 53.6 (13.1) and 63.4 (9.2) years, respectively. All cases with RA had received prior anti-TNF agents [mean (SD) number of anti-TNF agents 1.1 (0.8)]. During treatment with non anti-TNF, concomitant synthetic disease modifying drugs or glucocorticoids were received by 91.5% and 46.3% of cases, respectively. Only 7 cases (8.4%) received antiviral prophylaxis concomitant with non anti-TNF treatment (4 with lamivudine - 3 with entecavir). After a mean (SD) of 41.9 (24.6) months of follow-up and a mean (SD) of 18.0 (15.9) therapy cycles, one anti-HBc(+) anti-HBs(−) case experienced HBV reactivation 12 months after treatment with abatacept and was treated with tenofovir with good outcome. Of anti-HBs(+) patients at baseline, titers of anti-HBs antibodies did not show statistically significant delay from baseline to most recent follow-up (456.9 mIU/ml vs. 390.7 mIU/ml, respectively, p=0.08) (Figure 1).Figure 1ConclusionsOne case of HBV reactivation underlines the need for diligent monitoring in patients with serologic evidence of past HBV infection receiving non anti-TNF biologic agents. More data are needed to determine the need for universal prophylactic antiviral therapy in this subset of patients.Disclosure of InterestNone declared

Incidence of severe infection in patients with rheumatoid arthritis taking biologic agents: a systematic review

“…The major risk factors of severe infections are higher age, presence and number of comorbidities, 53 severity of RA, 27 increase in glucocorticoid dose, 28,60 history of biologic DMARD treatment, 50,53 and history of severe infection. 19,21 These risk factors could not be used for further analysis because the number of studies reporting the prevalence of risk factors was limited.…”

HBV reactivation in HBsAg−/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs

“…Abatacept has been reported to induce HBV reactivation, although its incidence has been inconsistent due to limited studies 6,18,24 . Six previous studies, that included 138 patients with resolved HBV infection who did not receive nucleoside analogue (NA) prophylaxis, found that only 10 patients experienced HBV reactivation during abatacept treatment, with varying incidence rates across the studies (ranging from 0% to 10.3%) 18,20,25–28 . Two large studies reported relatively high reactivation rates.…”

“…6,18,24 Six previous studies, that included 138 patients with resolved HBV infection who did not receive nucleoside analogue (NA) prophylaxis, found that only 10 patients experienced HBV reactivation during abatacept treatment, with varying incidence rates across the studies (ranging from 0% to 10.3%). 18,20,[25][26][27][28] Two large studies reported relatively high reactivation rates. In a prospective study from Japan, 3 of 29 HBsAg−/ HBcAb+ RA patients receiving abatacept experienced HBV reactivation (10.3%).…”

Risk of hepatitis B reactivation in HBsAg−/HBcAb+ patients after biologic or JAK inhibitor therapy for rheumatoid arthritis: A meta‐analysis

“…Twelve out of 26 articles also described the incidence of HBV reactivation in HBsAb− and HBsAb+ patients. Countries (number) of the studies were as follows: China (9), 1,3,6,[8][9][10][11][12][13] Italy (7), [14][15][16][17][18][19][20] Japan (6), 2,21-25 Korea (1), 26 Greece (1), 27 France (1), 28 and Multi-national (1). 29 Table 1 displays the basic characteristics of the 26 studies in our meta-analysis.…”