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

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.