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.
• Three phase 3 (VOYAGE 1, VOYAGE 2, NAVIGATE) 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 are seropositive for antibodies to hepatitis C virus (HCV) at screening.^1-3
• 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.^4,5
• A prospective study described the safety of TREMFYA in patients with comorbid PsO and HBV or HCV.⁶
• Case reports describing the use of TREMFYA in patients with comorbid hepatitis have been reported.^7-10

Clinical Data

Huang et al (2024)⁶ was 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 DNA, HCV RNA and alanine aminotransferase levels were assessed every 3 months during treatment and through 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 alanine amino transferase (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.¹¹
  • 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.¹¹
• 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 of 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.

Ch’en et al (2022)⁷ and Song et al (2021)⁸ described the case of a 13-year-old female from Guatemala with no known medical or family history.

Song et al (2021)⁸ reported that the patient initially presented with widespread plaque PsO (body surface area [BSA] involvement of 12% and static investigator global assessment [IGA] score of 3).

• No sufficient plaque PsO improvement seen with prior ultrapotent topical steroids and methotrexate treatment.
• The patient tested positive for hepatitis B (HB) surface antigen, HB core antibodies, and HB envelope antibodies, but negative for HB envelope antigen and HB surface antibodies.
• The patient’s HBV may have been congenitally acquired due to lack of HBV in the adopted family.
• HBV-deoxyribonucleic acid (DNA) load was 3.4 IU/mL (log 10).
• Liver function tests (aspartate aminotransferase [AST], 24; and alanine aminotransferase [ALT], 23) were in normal ranges.
• Ustekinumab 45 mg was initiated based on patient body weight of 160 lbs along with entecavir 0.5 mg daily.
• Six weeks after initiation of ustekinumab, a slight increase in liver enzymes (AST, 51; ALT, 77) and decrease in viral load (2.4 IU/mL [log 10]) were seen with no reported or observed abdominal pain, jaundice, itching, or flu-like symptoms.
• At the 28-week follow-up with treatment of ustekinumab, the patient presented to dermatologist with a 7% BSA involvement and an IGA 3 and was then switched to TREMFYA 100 mg.
• Following 1 dose of TREMFYA (4-week follow-up), the patient had 3% BSA and an IGA 3.
• At 12 weeks with treatment of TREMFYA, the patient had 1% BSA with an IGA 2. Her liver enzymes remained stable (AST, 26; ALT, 42) and viral load was undetectable.

Ch’en et al (2022)⁷ followed up on the case of the same patient after 36 weeks of treatment with TREMFYA. The patient presented with a BSA involvement of 2% and physician global assessment (PGA) of 2.

• The patient had low-grade transaminitis (AST, 80; ALT, 71), however her HBV-DNA load remained low (2.5 IU/mL [log 10]).
• TREMFYA treatment was discontinued at 39 weeks due to limited improvement.

Megna et al (2022)⁹ described the case of a 48-year-old male with PsA and a severe form of plaque PsO.

• Only partial and transitory improvement was seen with previous PsO treatments of topical therapies, cyclosporine, methotrexate, adalimumab, and infliximab.
• The patient tested positive for anti-HCV antibodies and presence of HCV-RNA (chronic HCV-infection; genotype group 2). Etanercept was initiated without significant increase in liver enzymes (AST, 45; ALT, 59).
• The patient’s PsO worsened, and he was switched to ustekinumab after liver function test revealed AST, 109; ALT, 78; and HCV-RNA 2.35 IU/mL (log 10).
• Six months after initiation of ustekinumab, the patient was diagnosed with PsA, and therapy was switched to golimumab. At this time, HCV-RNA levels were decreased
  (1.2 IU/mL [log 10]) and pathological findings were normal.
• Due to worsening of both PsO and PsA, other biologic treatments were attempted, including secukinumab, certolizumab, and ixekizumab.
• After discontinuation of ixekizumab, dermatological examination revealed erythromato-desquamative plaques (Psoriasis Area and Severity Index [PASI] 18 and 38% BSA involvement).
• Transaminases were within normal range and the patient achieved HCV-RNA clearance with pegylated interferon and ribavirin, so TREMFYA 100 mg administered subcutaneously at weeks 0, 4, and every 8 weeks thereafter was initiated.
• At 3 months, the patient showed improvement of skin manifestations (PASI, 2; BSA, 8%). Blood exams showed an elevation of liver enzymes (AST, 419; ALT, 321) and serum HCV-RNA returned positive (2.3 IU/mL [log 10]) with the same genotype, suggesting viral reactivation.
• TREMFYA treatment was discontinued. Sofosbuvir and ribavirin were initiated. After 4 months, liver enzymes returned to normal range and after 6 months, the patient achieved HCV-RNA clearance.

Messina et al (2022)¹⁰ described the case of 45- and 54-year-old male patients with chronic viral hepatitis who were receiving TREMFYA.

• Patient 1 (45 years old) presented with a medical history of both PsO and PsA for 31 years in addition to other comorbidities.
  • Human immunodeficiency virus (HIV) test results were negative; HBV and HCV test results were positive for serologic markers (anti-HB surface antigen, anti-HB core antigen, and anti-HCV) but HBV-DNA and HCV-RNA were undetectable.
  • Lamivudine 100 mg/day was provided as prophylactic treatment for HBV reactivation.
  • Ultrasonography showed no signs of cirrhosis.
  • The patient had a medical history of several systemic and biologic treatment options and due to PsO relapse (PASI 28), a switch from secukinumab to TREMFYA treatment was initiated.
  • At week 12, the patient presented with complete remission of both PsO (PASI 0) and PsA which was also present during the last follow-up presentation 20 months after the initiation of TREMFYA.
  • The patient was receiving prophylactic lamivudine during the treatment with TREMFYA.
  • Liver enzymes remained within normal range and no reactivation of HBV or HCV was reported.
• Patient 2 (54 years old) presented with a medical history of PsO for 27 years in addition to other comorbidities.
  • The patient tested positive for serological markers of past HBV infection and anti-HCV antibodies but negative for anti-HIV antibodies.
  • Patient also presented with HCV-related liver cirrhosis and in the past few years had undergone 3 successful HCV eradication therapies, but each showed signs of reinfection due to patient’s medical history of intravenous (IV) drug addiction.
  • Previous PsO treatments included narrowband ultraviolet B (NB-UVB), acitretin, ustekinumab, secukinumab, and ixekizumab.
  • TREMFYA was initiated for severe PsO relapse (PASI 23) and at the time HCV viremia was undetectable.
  • At week 12, the patient presented with PASI 6.
  • At 6 months, HCV viremia of 30,228 UI/mL was observed and antiviral treatment with glecaprevir + pibrentasvir was administered while continuing treatment with TREMFYA.
  • HCV eradication was observed in 3 months and after 18 months of follow-up, PsO was still under control (PASI 5) with no changes in liver function detected.  

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 15 March 2024.