Background/Purpose: Due to the use of immunosuppressants, patients with rheumatic diseases are at increased risk for Hepatitis B virus (HBV) reactivation. B-cell depleting agents and TNF-α inhibitors are known to be associated with increased risk of HBV reactivation. The risks of other biologic/targeted synthetic DMARDs are not well understood. Both Janus Kinase (JAK) inhibitors and Interleukin-6 (IL-6) inhibitors interfere with the IL-6 pathway, which is critical in the control of underlying HBV infection. We thus conducted a systematic review and meta-analysis on the incidence of HBV reactivation in patients with rheumatoid arthritis receiving JAK inhibitor or IL-6 inhibitor.

Methods: We systematically searched Pubmed/Medline and Embase from January 1, 2010-May 1, 2023, to identify eligible studies that examined Hepatitis B virus (HBV) reactivation among RA patients receiving L-6 inhibitor (Tocilizumab or Sarilumab) or JAK inhibitor (Baricitinib, Tofacitinib, Upadacitinib). Studies with information on RA patients with chronic (HBsAg+/anti-HbcAb+) or previously resolved (HBsAg-/anti-HbcAb+) status were included. Information on medication and interval of monitoring for HBV reactivation were also obtained. Hepatitis B reactivation was defined as > 10-fold increase HBV DNA level from baseline or positive HBV DNA which was previously negative. Meta-analysis was performed using R statistical software.

Results: The meta-analysis included 16 studies comprised of RA patients with previously resolved (n= 547) or chronic (n= 46) HBV infection. The proportion of users of JAK inhibitors among previously resolved HBV infection was 63% (n=362) and chronic HBV was 59% (n=27). Serial monitoring for HBV viral load and liver function tests ranged from every 4 weeks to 6 months. Among those with previously resolved HBV infection, the pooled incidence rate for HBV reactivation was 0.76% [95% CI 0.0017 – 0.0335]. In the subgroup analysis, users of JAK inhibitors showed lower reactivation rate compared to IL-6 inhibitors (0.2% vs 1.9%). Among those with chronic HBV infection, the pooled incidence rate for HBV reactivation was 26% (95% CI 0.14 – 0.44] with lower rate of HBV reactivation among those on JAK inhibitors compared to IL-6 inhibitors (19% vs 37%).

Conclusion: In this systematic review and meta-analysis, the risk of HBV reactivation among RA patients with previously resolved HBV infection was relatively low; however, the risk was higher among HbSAg carriers. In both groups, the use of JAK inhibitors was associated with lower risk of HBV reactivation compared to the use of IL-6 inhibitors. Additional studies with larger cohorts are still necessary to better inform rheumatologists managing these patients with underlying Hepatitis B infection.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-hepatitis-b-virus-reactivation-in-patients-with-rheumatoid-arthritis-receiving-jak-inhibitor-or-il-6-inhibitor-a-systematic-review-and-meta-analysis/