HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: a systematic review and meta-analysis

Abstract

Objective: The objective of this study was to assess the possibility of HBV reactivation (HBVr) in patients with RA under anti-IL-6 treatment.

Methods: Using PubMed, Scopus and EMBASE, we performed a systematic literature search for articles related to HBVr in RA patients under anti-IL-6 treatment. The search was performed with no date limits and was last updated 28 January 2023. The results from all the databases were combined and duplicates were excluded, as were non-English articles, case reports, position articles, comments, and paediatric studies.

Results: Our initial search led to 427 articles; 28 were duplicates, 46 non-English, 169 reviews, 31 books/letters, 25 case reports, and 88 irrelevant to the meta-analysis aim; 21 were excluded due to inadequate information, leaving 19 articles, with a sum of 372 RA patients with chronic HBV (CHB) or resolved HBV infection, for further analysis. The overall risk for HBVr in RA patients with CHB was 6.7%, increasing to 37% when only RA patients with CHB and no antiviral prophylaxis were included. On the contrary, HBVr was close to 0% in RA patients with resolved HBV infection, irrespective of antiviral prophylaxis. All RA patients experiencing HBVr in these studies were successfully managed with antiviral treatment and/or drug withdrawal.

Conclusion: Overall, anti-IL-6 treatment comes with a significant risk of HBVr in RA patients with CHB; risk is diminished when antiviral prophylaxis is used. In contrast, in RA patients with resolved HBV infection, the risk of HBVr seems to be extremely low. Large, well-designed studies (either controlled trials or multicentre/international observational studies) are warranted to further validate these results.

Keywords: HBV; HBV reactivation; RA; anti-IL-6; tocilizumab.