Can a patient with compensated (Child‑Pugh class A) liver cirrhosis be treated with Tremfya (guselkumab)?

Can Patients with Compensated Liver Cirrhosis Be on Tremfya?

Yes, patients with compensated (Child-Pugh A) liver cirrhosis can be treated with Tremfya (guselkumab), as the FDA label does not contraindicate its use in this population and does not require dose adjustments for hepatic impairment. 1

Key Safety Considerations

Hepatic Impairment and Tremfya

• The FDA label for Tremfya does not list cirrhosis or hepatic impairment as a contraindication, and no specific warnings or precautions are provided for patients with liver disease. 1
• Tremfya's only absolute contraindication is a history of serious hypersensitivity reaction to guselkumab or its excipients. 1
• No dose adjustments are specified in the prescribing information for patients with hepatic impairment, suggesting the drug can be used at standard dosing in compensated cirrhosis. 1

Monitoring Requirements in Cirrhotic Patients

• For patients with inflammatory bowel disease (ulcerative colitis or Crohn's disease), the FDA recommends evaluating liver enzymes and bilirubin at baseline, for at least 16 weeks of treatment, and periodically thereafter. 1
• Consider other treatment options in patients with evidence of acute liver disease or cirrhosis if treating inflammatory bowel disease; however, this recommendation applies to decompensated disease rather than compensated Child-Pugh A cirrhosis. 1
• Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction (jaundice, dark urine, light-colored stools, severe fatigue, or abdominal pain). 1

Infection Risk Considerations

• Tremfya may increase the risk of infection, with infections occurring in 23% of subjects in clinical trials versus 21% in placebo groups. 1
• In patients with compensated cirrhosis, who may have subtle immune dysfunction, evaluate for tuberculosis prior to initiating Tremfya and do not administer to patients with active TB infection. 1
• Treatment should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. 1

Clinical Context for Compensated Cirrhosis

Definition and Prognosis

• Compensated cirrhosis (Child-Pugh A) represents preserved hepatic function with median survival of 10-12 years, in contrast to decompensated cirrhosis with survival of only 1-2 years. 2
• Patients with compensated cirrhosis are largely asymptomatic and have not experienced decompensating events such as ascites, variceal hemorrhage, or hepatic encephalopathy. 3, 2

Important Distinction from Decompensated Disease

• The evidence provided focuses heavily on hepatitis C treatment in decompensated cirrhosis (Child-Pugh B or C), where protease inhibitors are absolutely contraindicated due to substantially higher drug exposure and risk of toxicity. 4
• However, Tremfya (guselkumab) is a monoclonal antibody targeting IL-23, not a protease inhibitor, and does not undergo the same hepatic metabolism pathways that make protease inhibitors dangerous in cirrhosis. 1

Practical Recommendations

Pre-Treatment Assessment

• Confirm Child-Pugh A status by documenting albumin >3.5 g/dL, bilirubin <2 mg/dL, INR <1.7, absence of ascites, and absence of encephalopathy. 3
• Screen for active infections, particularly tuberculosis, before initiating therapy. 1
• Ensure age-appropriate vaccinations are completed prior to starting Tremfya, avoiding live vaccines during treatment. 1

Monitoring During Treatment

• Monitor for signs of hepatic decompensation at each follow-up visit, including new ascites, jaundice, confusion, or bleeding. 3
• If treating psoriasis or psoriatic arthritis in a cirrhotic patient, standard monitoring applies without additional hepatic-specific requirements beyond baseline assessment. 1
• If treating inflammatory bowel disease, follow the FDA recommendation for liver enzyme and bilirubin monitoring at baseline, through 16 weeks, and periodically thereafter. 1

When to Avoid or Discontinue

• Do not use Tremfya if the patient has progressed to decompensated cirrhosis (Child-Pugh B or C), as the risk-benefit profile becomes less favorable and alternative treatments should be considered. 1
• Discontinue immediately if serious hypersensitivity reactions occur, including anaphylaxis. 1
• Interrupt treatment if drug-induced liver injury is suspected until this diagnosis is excluded. 1