The incidence of hepatitis B reactivation in patients receiving ustekinumab: a systematic review and proportional meta-analysis.

Background: This meta-analysis will evaluate the risk of hepatitis B reactivation in patients treated with ustekinumab for inflammatory bowel disease and psoriasis. We aim to determine the true incidence of this adverse event, reconcile discrepancies in reported reactivation rates, and elucidate the associated risk.

Methods: We conducted a rigorous systematic review adhering to established guidelines. Major databases like MEDLINE, Google Scholar, CENTRAL, and ClinicalTrials.gov were searched. Studies involving patients with documented hepatitis B infection undergoing ustekinumab therapy were included. Patients receiving concurrent antiviral medications were excluded. To account for potential underreporting, studies without reactivation events or with sample sizes ≥3 were also considered by using generalized linear mixed models and Clopper-Pearson confidence intervals. This review was prospectively registered in PROSPERO (CRD42023418130).

Results: We analyzed data from nine studies involving 104 hepatitis B virus (HBV)-infected patients. The pooled HBV reactivation (HBVr) incidence among hepatitis B surface antigen-positive patients was 10% [95% confidence interval (CI): 0-31%], with low heterogeneity (I2 = 7.13%, τ2 = 0.4) and a nonsignificant Q-statistic (Q = 5.38, P = 0.37). For the occult HBV-infected patients, the pooled HBVr incidence was 3% (95% CI: 0-11%), with no heterogeneity (I2 = 0%, τ2 = 0.0) and a nonsignificant Q-statistic (Q = 2.7, P = 0.61). The reactivation rates showed high consistency across studies, with no significant difference between the two groups.

Conclusions: While our data suggest lower HBVr risk with ustekinumab, confirmation is needed due to limited sample size and retrospective design.