Risk of Tuberculosis and Hepatitis B Reactivation in Patients With Crohn’s Disease on Ustekinumab: A Nationwide Real-World Study

Abstract

Background Ustekinumab (UST) was approved in China for moderate-to-severe Crohn’s disease (CD) in 2020. The prevalence rates of tuberculosis and hepatitis B virus (HBV) infection are high in China, and no guideline clearly states that tuberculosis chemoprophylaxis or prophylactic anti-HBV therapy should be prescribed before UST administration. This study aimed to assess the risk of tuberculosis and HBV reactivation in CD patients with latent tuberculosis infection (LTBI) and previous HBV infection receiving UST. Methods A multicenter retrospective cohort study was carried out at 68 hospitals in China to assess 721 adult CD cases administered UST between May 1, 2020, and December 31, 2021. CD and concurrent LTBI or HBV carrier were included. Hepatitis B serology, T-SPOT.TB, and tuberculin skin tests were performed at baseline. The primary outcome was tuberculosis or HBV reactivation. Results Patients with CD-concomitant LTBI or who were HBV carriers receiving UST therapy were retrospectively enrolled from 15 hospitals in China. A total of 53 CD with LTBI patients and 17 CD with HBV carrier patients receiving UST were included. Treatment and follow-up durations were 50 ± 20 weeks and 50 ± 15 weeks in the LTBI and HBV carrier groups, respectively. A total of 25 CD patients with LTBI underwent chemoprophylaxis and 28 did not. A total of 11 HBV carriers had antiviral prophylaxis and 6 did not. No patient experienced tuberculosis or HBV reactivation or liver dysfunction during follow-up. Conclusions UST was safe for treatment of CD because no patient developed tuberculosis, persistent hepatitis, or acute liver failure during therapy, whether with a prophylactic regimen or not, based on our sample size and limited follow-up time.

Clinical Data on Laboratory Testing for Patients Taking Systemic Immunomodulatory Agents

“…3,4 The IL-12/23 inhibitor ustekinumab has similarly been noted to have a lower risk profile. 5 Targeting the IL-13/IL-4R axis (eg, dupilumab) is hypothesized to not disrupt granuloma homeostasis; therefore, it should not elevate risk for reactivation of latent TB. 6 Apart from biologics, to our knowledge, no cases of latent TB reactivation have been reported in patients with long-term apremilast exposure, 7 whereas cases of patients developing TB while taking MTX have been reported.…”

“…Biologic agents targeting alternative pathways, specifically those involving IL-17 and IL-23, appear to be associated with lower rates of reactivation of latent TB compared with TNFi . The IL-12/23 inhibitor ustekinumab has similarly been noted to have a lower risk profile . Targeting the IL-13/IL-4R axis (eg, dupilumab) is hypothesized to not disrupt granuloma homeostasis; therefore, it should not elevate risk for reactivation of latent TB .…”