Ustekinumab Is Safe in Crohn Disease With Latent TB or Inactive Chronic HBV

While biologic treatment typically increases risk for reactivation of latent TB or previous HBV, ustekinumab was found to be safe and efficacious for CD without increasing risk.

Ustekinumab is safe and efficacious in patients with Crohn disease (CD) and latent tuberculosis infection (LTBI) or previous chronic hepatitis B virus (HBV) infection, according to a study in Inflammatory Bowel Diseases.

The retrospective cohort study compared the incidence rates of TB and HBV reactivation after ustekinumab therapy in patients who received TB chemoprophylaxis or prophylactic anti-HBV therapy with those who had no TB chemoprophylaxis or no prophylactic anti-HBV therapy.

The study was conducted at 68 academic hospitals and enrolled patients aged at least 18 years and diagnosed with CD and concurrent LTBI or past HBV infection who received ustekinumab. The main outcome was tuberculosis or HBV reactivation.

A total of 721 patients with CD received ustekinumab, of whom 53 patients had LTBI, with a mean [SD] age of 38[13] years and 35 (66%) men. The mean duration of ustekinumab treatment was 50 weeks. Of the 53 patients with LTBI, 25 patients had TB chemoprophylaxis and 28 did not. The mean follow-up duration for the 53 patients with or without TB chemoprophylaxis was 42 and 58 weeks, respectively. No active TB was observed in either group.

TB chemoprophylaxis therapy does not affect the treatment effectiveness of ustekinumab.

A total of 14 patients had inactive HBV infection and 3 had previous HBV infection. These 17 patients had a mean age of 37.7[11.1] years, and 13 (76.5%) were men. Their mean CD duration was 3.94 years.

Among the 17 patients, 6 had no antiviral prophylaxis, 8 had antiviral prophylaxis with entecavir, and 3 had antiviral prophylaxis with tenofovir. The mean follow-up in this group was 50 weeks, and liver function was evaluated at each ustekinumab administration. The patients had no overt increases in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, or total bilirubin levels, and no liver dysfunction occurred during the follow-up.

For the 6 patients who were diagnosed with inactive HBV infection before ustekinumab treatment initiation and did not receive antiviral prophylaxis, the mean follow-up was 53 weeks vs 48 weeks in the 11 patients who received antiviral prophylaxis. The 2 groups had no active HBV infection.

Analysis of effectiveness included 52 patients, with 16 patients with CD and HBV infection and 36 patients with CD and LTBI. Among these 52 patients, 12 had baseline Crohn Disease Activity Index (CDAI) scores lower than 150. For the other 40 patients, CDAI scores had a progressive decrease at each assessment. Corticosteroid-free clinical response and remission rates at week 8 were 55% and 37.5%, respectively, compared with 61.8% and 47.1% at week 20, 79.2% and 54.2% at week 32, 82.4% and 52.9% week 44, and 75% and 58.3% at week 56, respectively.

Limitations include the absence of control groups without LTBI or HBV infection, so TB and HBV infection risk in all CD patients on ustekinumab could not be assessed. In addition, further research with more patients and extended follow-up are needed to confirm the findings.

“In some cases, TB chemoprophylaxis or prophylactic anti-HBV therapy is not required for CD patients with LTBI or past chronic HBV infection,” the researchers wrote. “TB chemoprophylaxis therapy does not affect the treatment effectiveness of ustekinumab.”

This article originally appeared on Gastroenterology Advisor


Liu R, Li Z, Ye L, et al. Risk of tuberculosis and hepatitis B reactivation in patients with Crohn’s disease on ustekinumab: a nationwide real-world study. Inflamm Bowel Dis. Published online March 6, 2023. doi:10.1093/ibd/izad032