Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Specific studies have not been conducted in patients with hepatic insufficiency.¹
• Summaries of a prospective study and retrospective studies published in the literature are described below.^2-8  

company core data sheet

Specific studies have not been conducted in patients with hepatic insufficiency.¹

CLINICAL DATA

Prospective Study

Ting et al (2018)² conducted a prospective cohort study to evaluate the risk of hepatitis B virus (HBV) reactivation in patients with moderate to severe psoriasis (PsO) with varying HBV status who received STELARA treatment.

• At baseline, all patients were tested for hepatitis B serology and serum viral deoxyribonucleic acid (DNA).
• HBV status of each patient was classified into one of the following 6 categories:
  • Naïve to HBV
  • Vaccinated
  • Inactive HBV carrier
  • Chronic active hepatitis B
  • Resolved HBV infection
  • Isolated anti-hepatitis B core (HBc) positivity
• Patients received STELARA 45 mg subcutaneously (SC) at weeks 0 and 4, and then every 12 weeks.
• Serum alanine aminotransferase (ALT) levels were measured before each STELARA administration.
• HBV reactivation was defined as:
  • A marked increase in HBV replication (>2 log increase from baseline levels)
  • A new appearance of HBV DNA at a level of >100 IU/mL in a person with previously stable or undetectable levels
  • Detection of HBV DNA at a level >20,000 IU/mL in a person with no baseline HBV DNA
• Hepatitis was defined as an ALT level exceeding 2 times the upper limit of normal (40 IU/L).
• A total of 93 patients were included and the average duration of follow-up was 24±12 months.
  • Of these, a total of 39 were naïve to HBV (n=20) or vaccinated (n=19), and none of these patients had HBV reactivation during STELARA treatment.
  • The other 54 patients were classified as resolved HBV infection (n=38), inactive HBV carriers (n=10), or isolated anti-HBc positivity (n=6).
    • Among these, a total of 3 patients, none of whom received antiviral prophylaxis, experienced HBV reactivation (2 in the inactive HBV carrier group, both without hepatitis, and 1 in the resolved HBV infection group with mild hepatitis). None of these patients had liver failure.
    • Two patients in the inactive HBV carrier group who did not receive prophylaxis experienced viral reactivation without hepatitis.
      • The first patient experienced 2 episodes of virologic reactivation, 6 and 28 months after STELARA, respectively. The patient received lamivudine for 30 days during the second reactivation, achieving a rapid drop in viral load.
      • The second patient had viral reactivation 3 months after STELARA with low levels of serum HBV DNA fluctuating between 72 and 600 IU/mL and did not receive any antiviral treatment.
    • One patient in the resolved HBV infection group experienced virologic reactivation with mild hepatitis (peak ALT of 87 IU/L) 12 months after STELARA treatment. The patient received concurrent methotrexate (MTX) during reactivation. The patient’s serum HBV DNA became undetectable without antiviral therapy 6 months after MTX discontinuation.
  • A total of 2 of the 93 patients received antiviral prophylaxis (in the inactive HBV carrier group) and of these none had HBV reactivation.

Retrospective Studies

Liu et al (2024)³ conducted a retrospective, multicenter study to evaluate the incidence of HBV reactivation in patients with Crohn’s disease (CD) treated with STELARA, with or without prophylactic anti-HBV therapy. The safety and efficacy of STELARA in patients with CD with past HBV infection were also assessed. Results specific to HBV are summarized below.

• A total of 52 patients were included in the effectiveness analysis, of whom 17 patients with CD reported HBV infection.
• The patients were screened for HBV infection before initiating treatment with STELARA.
• Liver function was assessed for all the patients at every STELARA administration, while HBV DNA was monitored for the patients with past HBV infection every 3 to 6 months.
• HBV status was classified according to the European Association for the Study of Liver Disease into the following 4 categories:
  • Active chronic HBV infection (HBsAg positive and HBV DNA positive)
  • Inactive chronic HBV infection (HBsAg positive and HBV DNA negative)
  • Past HBV infection (HBsAg negative, hepatitis B surface antibody [HBsAb] positive, and [HBcAb] positive)
  • Isolated core antibody positivity (HBsAg negative, HBsAb negative, and HBcAb positive)
• HBV reactivation was defined as an increase in HBV DNA levels in patients with viremia or the reappearance of HBV DNA in patients who previously had no detectable viral DNA.
• Among the 17 patients with CD, 4 (23.5%) were female and 13 (76.5%) were male, with a mean age of 37.7 ± 11.1 years.
• Fourteen patients reported an inactive HBV infection, while 3 had a history of HBV infection.
• All patients had serum HBV DNA levels below 2000 IU/mL.
• Of these 17 patients:
  • Six did not receive antiviral prophylaxis (mean duration of follow-up, 53 weeks).
  • Eleven received antiviral prophylaxis (8 with entecavir, 3 with tenofovir; mean duration of follow-up, 48 weeks).
  • No overt increases in ALT, aspartate aminotransferase (AST), gamma-glutamyl transferase, alkaline phosphatase, or total bilirubin levels were observed. No liver dysfunction was observed during follow-up.
  • No case of active HBV infection was reported in either group.

Lu et al (2024)⁴ assessed a retrospective, multicenter, observational real-world study evaluating the reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive HBV infection in patients with plaque PsO treated with STELARA for 28 weeks.

• Inclusion criteria: adult patients with moderate to severe plaque PsO who met 1 of these following criteria: body surface area (BSA) ≥3% or psoriasis area and severity index (PASI) ≥3.
• All patients were screened for HBV infection at baseline and monitored every 3 months using serological examination.
• Exclusion criteria: active tuberculosis infection and active HBV infection.
• Patients with LTBI and inactive HBV infection were included in the study and underwent preventive treatment with entecavir.
• Patients weighing ≤100 kg received STELARA 45 mg SC at week 0 and week 4, followed by 45 mg SC every 12 weeks and patients weighing >100 kg received 90 mg SC at week 0 and week 4, followed by 90 mg SC every 12 weeks.
• Inactive HBV infection was defined as hepatitis B surface antigen (HBsAg) positive with HBV DNA negative and normal liver function or isolated hepatitis B core antibody (HBcAb) positive with HBV DNA negative and normal liver function.
• Reactivation of HBV was defined as meeting ≥1 of these criteria:
  • HBV DNA load increased >100-fold vs baseline
  • Detection of HBV DNA in patients with no baseline of HBV DNA
  • HBsAg positive in patients with a history of HBsAg negative
  • Liver dysfunction (≥3-fold increase in ALT vs baseline or absolute ALT >100 U/L)
• A total of 82 patients were included in the study. Of the total population, 21 patients with inactive HBV infection.
  • Among 21 patients with inactive HBV infection, 6 patients were exposed to both LTBI and inactive HBV infection, simultaneously.
• No cases of reactivation or new HBV infection were reported during the treatment period.

Klujszo et al (2022)⁵ presented observations on the safety of STELARA treatment in patients with moderate to severe PsO and serologically proven past HBV infection.

• A total of 106 patients were included in the retrospective analyses. Of these patients,
  5 reported having a past HBV infection.
• The 5 patients having reported past HBV infection were tested for the presence of HBsAg, HBcAb, HBsAb, and HBV DNA at baseline and at the end of follow-up period.
• HBV reactivation was defined as a changing of “undetectable” to “detectable” viremia.
• The cut-off for HBsAb positive status was >10 IU/mL HBV DNA.
• Patients who were negative for HBsAg, positive for HBcAb, and negative for HBV DNA were classified as past HBV infection regardless of HBsAb status.
• Baseline liver function tests (LFTs) were within normal range for each of the patients.
• No patients experienced an increase in LFTs and no signs of hepatitis or HBV reactivation were observed.
• Serological HBV evaluation for each patient is described in Table: HBV Infection Serological Markers

• The average treatment time was 82.4 (28, 96) weeks and the average follow-up time was 75.2 (31, 176) weeks.

Siegel et al (2019)⁶ retrospectively reviewed a cohort of patients treated with STELARA who were infected with HBV and/or hepatitis C virus (HCV).

• A total of 18 adult patients (13 men, 5 women; age 23-60 years) who had received at least 2 doses of STELARA for PsO (17 with plaque-type PsO and 1 with palmar/plantar type PsO; 9 with concurrent psoriatic arthritis [PsA]) were included in this review (see Table: Features of Patients With HBV, HCV, or HBV/HCV Coinfection During STELARA Treatment).
• Of these 18 patients, 7 had HBV infection alone (3 received concurrent antiviral therapy), 3 were coinfected with HBV and HCV (2 received concurrent antiviral therapy for HBV), and 8 were infected with HCV alone.
  • Four of the HCV⁺ patients had biopsy-proven cirrhosis at the start of therapy.
  • Of the 11 patients with HCV or HBV/HCV infection, 3 were treated for HCV before and during STELARA use.
• There was no evidence of viral reactivation or significant elevations in liver enzymes (defined by 10-fold increase in viral load and/or threefold increase in serum ALT, between baseline and the maximum recorded value) based on serial monitoring of serum transaminases and viral DNA/ribonucleic acid (RNA) levels.
  • The exception was patient 10, who was diagnosed with a relapse of HCV infection 6 months post-antiviral therapy; it is unknown if this reactivation was related to STELARA.
• At the time of the report, 11 patients remained on STELARA treatment while 7 patients discontinued therapy due to unsatisfactory skin clearance results.

Chiu et al (2013)⁷ retrospectively evaluated STELARA in the treatment of patients with PsO with concurrent HBV or HCV infection.

• A total of 18 patients (HBV, n=14; HCV, n=4) who received ≥2 STELARA injections were included in the study.
• Patients received STELARA 45 mg SC at weeks 0 and 4, and then once every 2-3 months for maintenance treatment.
• At baseline and at least each time before each STELARA injection, HBV DNA/HCV RNA levels were assessed.
• ALT/AST was evaluated in patients with viral reactivation.
• Out of the 11 patients positive for HBsAg, there were 7 patients who did not receive prophylactic antiviral treatment and 4 patients who did receive antiviral prophylaxis.
  • Two of the 7 patients without antiviral prophylaxis had HBV reactivation while receiving STELARA.
  • As AST/ALT elevation did not occur in these 2 cases, they were classified as a very mild reactivation.
  • One of the 2 patients with reactivation subsequently received entecavir 0.5 mg daily and the viral load decreased rapidly within 3 months of therapy (after preemptive therapy was deferred until the detection of virological reactivation).
  • The other patient with HBV reactivation received follow-up with a hepatologist without antiviral therapy.
  • None of the 4 patients with antiviral prophylaxis (entecavir 0.5 mg daily) had HBV reactivation during STELARA treatment and their serum viral loads decreased.
• No HBV reactivation was reported in the 3 occult HBV infected patients (HBsAg-negative/HBcAb-positive). None of these patients received antiviral prophylaxis.
• Of the 4 patients with concurrent HCV infection, 1 case of HCV reactivation during STELARA treatment was reported.
  • In this case, the patient developed HCV reactivation after 1 month and recurrence of hepatocellular carcinoma (HCC) after 4 months of STELARA treatment.
  • The patient had liver cirrhosis 5 years prior to STELARA treatment.
  • There was no elevation in the patient’s liver function tests.
  • STELARA was discontinued after the patient’s HCC recurrence and the patient underwent transarterial chemoembolization.
• PASI 75 (a 75% improvement from the baseline PASI) was achieved in 5 of the 14 patients with PsO and HBV infection and 0 of the 4 patients with PsO and HCV infection during STELARA treatment.

Navarro et al (2013)⁸ conducted a retrospective, multicenter study evaluating the safety and efficacy of STELARA and anti-tumor necrosis factor (TNF) therapy in patients with PsO and chronic HBV or HCV infection.

• A total of 25 adult patients with PsO and concurrent HBC or HBV infection were included (HCV, n=20; HBV, n=5). Of these total population, 3 patients with HCV infection and 1 patient with HBV infection received treatment with STELARA.
• The 3 patients with HCV infection treated with STELARA all had plaque-type PsO (baseline PASI scores ranged from 18.6-34) with disease duration of 3-10 years and a history of HCV of 7-14 years.
  • None had received treatment for HCV.
  • Two of the patients were also receiving isoniazid and antiretrovirals concomitantly.
  • The duration of STELARA treatment ranged from 12-17 months.
  • One patient experienced a slight increase in viral load, and AST and ALT were increased in another patient. There were no serious adverse events (AEs) reported.
  • A 75% or greater reduction in PASI score (PASI 75) was achieved at the end of therapy in 2 of the 3 patients; no data were available for the third patient.
• Only 1 patient with plaque PsO and HBV infection received STELARA. That patient had a 10-year history of PsO (baseline PASI was 17.6) and a 2-year history of HBV infection.
  • The patient had hepatic steatosis and was an alcoholic and obese.
  • He received antiviral treatment with entecavir and received STELARA for 7 months.
  • Viral load decreased from 2000 at baseline to 0 at the end of evaluation.
  • AST and ALT remained stable and there were no serious AEs reported.
  • PASI 75 was achieved at the end of therapy.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 29 April 2025.