TREMFYA - Use in Adult Patients with Plaque Psoriasis or Psoriatic Arthritis and Comorbid Hepatitis

SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Please refer to the local labeling for relevant infection-related information for TREMFYA.
• Five phase 3 (VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, and ECLIPSE) multicenter, randomized, double-blind clinical studies for the treatment of adult patients with moderate-to-severe plaque psoriasis (PsO) excluded patients who tested positive for hepatitis B virus (HBV) infection or who were seropositive for antibodies to hepatitis C virus (HCV) at screening.^1-5
• Two randomized, double-blind, placebo-controlled, multicenter, phase 3 studies (DISCOVER-1 and DISCOVER-2) for the treatment of adult patients with active psoriatic arthritis (PsA) excluded patients who tested positive for HBV infection or who were seropositive for antibodies to HCV at screening, unless the patient had 2 negative HCV ribonucleic acid (RNA) tests results at least 6 months apart prior to screening and had a third negative HCV RNA test result at screening.^6,7
• A prospective study and 3 retrospective studies described the safety of TREMFYA in patients with comorbid PsO and HBV or HCV.^8-11

Clinical Data

Prospective Study

Huang et al (2024)⁸ conducted a prospective, multicenter study that evaluated the safety of TREMFYA in patients with PsO and HBV or HCV.

Study Design/Methods

• Patients received TREMFYA 100 mg at week 0 and 4 and then every 8 weeks between June 2018 and November 2021 at two dermatology centers.
• Prior to treatment, HBV and HCV serological markers were screened.
• HBV deoxyribonucleic acid (DNA), HCV RNA, and alanine aminotransferase levels (ALT) were assessed every 3 months during treatment and through the end of treatment or follow-up.

Results

• Of the 92 patients treated with TREMFYA, 84 patients and 8 patients had HBV and HCV, respectively. The following table highlights select baseline demographics and disease characteristics: Baseline Demographics and Disease Characteristics in Patients with HBV or HCV Infection.

• There were 13 patients who were positive for hepatitis B surface antigen (HBsAg⁺).
  • Among the 10 patients who did not receive antiviral prophylaxis, 1 patient experienced HBV reactivation.
    • Patient was a 44-year-old male with a 4-year history of PsO and was biologic-naïve prior to TREMFYA treatment. Baseline ALT, baseline viral load, and viral load at reactivation were 40 IU/L, 4071 IU/mL, and 44,200 IU/mL, respectively. Time to reactivation was 12 months. The patient was followed up for 21 months.¹²
  • Three patients received entecavir or telbivudine antiviral prophylaxis. One patient discontinued antiviral prophylaxis and later developed HBV reactivation.
    • Patient was a 42-year-old male with a 26-year history of PsO and was biologic-experienced (ustekinumab, adalimumab, secukinumab) prior to TREMFYA treatment. Baseline ALT, baseline viral load, and viral load at reactivation were 78 IU/L, 0 IU/mL, and 161 IU/mL, respectively. Time to reactivation was 21 months. The patient was followed up for 27 months.¹²
• Both patients (n=2/13, 15.3%) who experienced HBV reactivation were positive for hepatitis B e antigen (HBeAg⁺) and negative for antibody against hepatitis B e antigen (anti-HBe^-).
  • The 2 patients did not develop hepatitis, experienced decrease in HBV DNA levels without antiviral therapy, and maintained TREMFYA treatment without changes.
• Of the 71 patients who were negative for hepatitis B surface antigen (HBsAg^-), none received antiviral prophylaxis or experienced HBV reactivation.
• The HBV reactivation rate was higher in the patients with HBsAg⁺ when compared to the patients with HBsAg^- (15.3% vs 0%, P<0.001).
• Of the 8 patients with HCV, none experienced HCV reactivation.

Retrospective Studies

Aygar et al (2025)⁹ conducted a retrospective analysis to evaluate the risk of reactivation of HBV in patients with PsO receiving systemic immunosuppressive therapy who had either resolved HBV infection or isolated anti-hepatitis B (anti-HB) core immunoglobulin G positivity.

Study Design/Methods

• Adult patients (≥18 years) with PsO vulgaris receiving systemic immunosuppressive therapy, such as methotrexate, apremilast, cyclosporine, or biologics (such as tumor necrosis factor [TNF]-α inhibitors, interleukin [IL]-17 receptor blockers, IL-17A inhibitors, anti-IL-12/23, and anti-IL-23 agents), for ≥3 months were included.
• For eligibility criteria, see Table: Inclusion and Exclusion Criteria.
• Patients were grouped into HBV reactivation risk categories based on serologic status and the immunosuppressive agent used: group 1, low risk (<1%); group 2, moderate (1-10%); group 3, high (≥10%).
• Liver function tests (ALT and aspartate aminotransferase) were performed approximately every 3 months to monitor for signs of active hepatitis. In cases of elevated liver enzymes, HBsAg and HBV DNA levels were assessed.
• HBV reactivation was defined as HBsAg seroconversion or detectable HBV DNA in serum. Anti-HBs titers were categorized as <10 IU/L, 10-99 IU/L, and ≥100 IU/L, and their association with HBV reactivation was evaluated.

Results

• Of the 138 patients treated with immunosuppressive agents, 13 (9.4%) received TREMFYA for a mean±SD (range) duration of 22.5±19.88 (3-82) months.
• Within the moderate-risk group, 11 of 87 patients received TREMFYA.
• Among high-risk patients receiving concurrent antiviral prophylaxis with immunosuppressive therapy, 2 of 6 patients received TREMFYA.
• In the high-risk group, HBV reactivation was reported in one patient receiving TREMFYA (39-year-old male; time to reactivation, 12 months; prophylactic agent, tenofovir).

Lu et al (2025)¹⁰ conducted a retrospective, observational study to evaluate the safety of biologics targeting IL-12/23 or IL-23 in Chinese patients with PsO combined with latent tuberculosis infection (LTBI) or inactive HBV infection.

• The study included 220 patients with PsO from 3 hospitals in China and were divided into 2 groups:
  • TREMFYA group included 86 patients (including 16 patients with inactive HBV infection and 14 patients with LTBI)
  • Ustekinumab group included 134 patients (including 37 patients with inactive HBV infection and 27 patients with LTBI)
• During treatment, 14 patients with inactive HBV infection or LTBI did not receive antituberculosis or antiviral hepatitis B prophylaxis.
• During the 1-year follow-up period, no cases of active HBV infection or LTBI reactivation were observed in either group. See Fig: Patient Disposition and Follow-up in Patients Treated with TREMFYA.

Mortato et al (2025)¹¹ conducted a retrospective, multicenter, real-world longitudinal study to evaluate the clinical outcomes and safety of TREMFYA in patients with concomitant chronic infection, cancer, or heart disease.

Study Design/Methods

• All patients received 2 doses of TREMFYA for ≥12 weeks: an induction dose of 100 mg subcutaneously at weeks 0 and 4, followed by maintenance dosing every 8 weeks.
• For eligibility criteria, see Table: Inclusion and Exclusion Criteria in EARLY Study.
• Patients with prior or active HBV or HCV infections were regularly monitored for viral reactivation or risk of hepatic fibrosis.
• Liver enzyme tests were performed every 6 months. In seropositive patients, the markers (HBV DNA, antibody to HBsAg, antibody to HB core antigen, HBsAg, anti-HCV, HCV RNA) were re-evaluated every 6 to 12 months, followed by an annual hepatology consultation.

Results

• Among the 1024 patients, 77 (7.5%) had a history of HBV infection and were categorized according to the following serological profiles:
  • Group 1 (51 patients): resolved HBV (HBsAg^–, hepatitis B surface antibody [HBsAb]⁺, hepatitis B core antibody [HBcAb]⁺, HBV DNA^–); 47 patients did not require antiviral therapy during TREMFYA treatment, whereas 4 received lamivudine
  • Group 2 (18 patients): isolated HBcAb positivity (HBsAg^–, HBsAb^–, HBcAb⁺, HBV DNA^–), suggestive of past HBV exposure without full immune protection, which may occur in cases of resolved infection, immunosuppressive therapy, or occult HBV; 16 patients did not require antiviral therapy, whereas 2 received unspecified antiviral treatment
  • Group 3 (8 patients): active chronic HBV (HBsAg^+/–, HBsAb^+/–, HBcAb⁺, HBV DNA⁺); all patients received antiviral therapy
• HCV infection was present in 28 patients (2.7%). Of these, 18 patients were HCV RNA⁺ with an active infection and received antiviral therapy. The remaining 10 patients were HCV RNA^–, indicating resolved HCV infection, either due to spontaneous clearance or successful treatment.
• The mean (SD) follow-up duration for all patients with HBV and HCV was 130.1 (84.7) weeks and 124.6 (72.0) weeks, respectively.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 5 February 2026.

Summarized in this response is a prospective study and 3 retrospective studies pertaining to this topic.