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

Abstract

Background The risk of hepatitis B virus (HBV) reactivation after biologic and targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs) therapy in patients with rheumatoid arthritis (RA) combined with HBsAg–/HBcAb+ is still inconsistent. Methods We conducted a systematic review of existing databases from 1977 to August 22, 2021. Studies of RA patients combined with HBsAg−/HBcAb +, treated with b/tsDMARDs and the reported number of HBV reactivation were included. Results We included 26 studies of 2252 HBsAg−/HBcAb+ RA patients treated with b/tsDMARDs. The pooled HBV reactivation rate was 2.0% (95% confidence interval [CI]: 0.01−0.04; I 2 = 66%, p < .01). In the subgroup analysis, the HBV reactivation rate of rituximab (RTX), abatacept, and inhibitors of Janus kinase (JAK), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) were 9.0% (95% CI: 0.04−0.15; I 2 = 61%, p = .03), 6.0% (95% CI: 0.01−0.13; I 2 = 40%, p = .19), 1.0% (95% CI: 0.00−0.03; I 2 = 41%, p = .19), 0.0% (95% CI: 0.00−0.02; I 2 = 0%, p = .43), 0.0% (95% CI: 0.00−0.01; I 2 = 0%, p = .87), respectively. While HBsAb‐ patients have a significant risk of reactivation (odds ratio [OR] = 4.56, 95% CI = 2.45−8.48; I 2 = 7%, p = .37), low HBsAb+ group also display a significant risk of reactivation (OR = 5.45, 95% CI: 1.35−21.94; I 2 = 0%, p = .46). Conclusions This meta‐analysis demonstrates the highest potential risk of HBV reactivation in HBsAg−/HBcAb+ RA patients receiving RTX treatment, especially HBsAb− patients. Our study furthers the understanding of the prophylactic use of anti‐HBV drugs in such patients. However, it is relative safety to use the inhibitors of IL‐6, TNF‐α, and JAK in these patients.

Long-term safety of biologic and targeted synthetic disease modifying drugs in rheumatology

“…An observational study of hepatitis B (HBV) reactivation in HBsAg À /HBcAb þ patients treated with various biologics found a pooled reactivation rate of 2.0%, with a 6.0% risk (95% CI 0.01-0.13) with abatacept, second only to rituximab (9% risk, 95% CI 0.04-0.15). Significantly lower rates of HBV reactivation were seen with JAKi, IL-6i, and TNFi [30].…”

Upadacitinib-Induced Hepatitis B Reactivation Leading to Liver Transplant

“…9,10 A meta-analysis involving patients with RA receiving diseasemodifying antirheumatic drugs who were HBsAg-negative and HBcAb-positive was found to have a 1.0% pooled reactivation rate with JAK inhibitors. 11 A retrospective cohort study of patients receiving tofacitinib was able to show that 2 of the 6 HBsAg-positive patients developed HBVr. 12 HBVr with ruxolitinib use has also been documented.…”

The Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Receiving Tocilizumab: A Systematic Review and Meta-Analysis

“…The HBV reactivation rate was lower in HBsAg − /anti-HBc + individuals without antiviral prophylaxis. In a recent meta-analysis of HBsAg − /anti-HBc + patients with rheumatoid arthritis receiving IL-6 inhibitor therapy, the pooled reactivation rate was found to be 0.0% (4 studies; 1 reactivation in 162 patients; I 2 , 0%; P, 0.43) [ 11 ]. However, our own meta-analysis, which included a greater number of studies and a larger sample size (11 studies; 4 reactivations in 322 patients), demonstrated that this population still has a notable risk of HBV reactivation.…”

“…Several studies have addressed the risk of HBV reactivation in patients with severe COVID-19 receiving TCZ therapy [ 9 , 10 ]. The risk seems low in patients who are HBV-surface-antigen–negative/HBV-core-antibody–positive (HBsAg − /anti-HBc + ), and a short course of antiviral prophylaxis may be a safe option [ 11 ]. A study investigating the outcomes of 44 HBsAg − /anti-HBc + COVID-19 patients treated with tocilizumab [ 9 ] found that 61% of these patients received prophylactic entecavir.…”

“…This variability complicates clinical decision-making regarding antiviral prevention or close monitoring. Although a recent meta-analysis reported a pooled reactivation rate of 0.0% ( I 2 , 0%; P, 0.43) [ 11 ], it is important to note that this analysis was based on only 4 studies and a search just through 2021. Therefore, an updated search is needed to include a broader range of studies to strengthen the existing evidence.…”