Is ocrelizumab (ocrelizumab) safe to use in patients with liver cirrhosis?

Safety of Ocrelizumab in Patients with Liver Cirrhosis

Ocrelizumab should not be used in patients with decompensated liver cirrhosis, but may be used with caution in patients with compensated liver cirrhosis with close monitoring of liver function. 1, 2

General Considerations for Drug Use in Cirrhosis

• Liver cirrhosis significantly alters drug pharmacokinetics and pharmacodynamics, requiring careful consideration of medication safety and dosing adjustments 2, 3
• Patients with cirrhosis are more susceptible to adverse drug reactions due to impaired drug metabolism and elimination 2, 4
• The FDA label for ocrelizumab states that patients with mild hepatic impairment were included in clinical trials with no significant changes in pharmacokinetics observed 1

Ocrelizumab in Compensated Liver Cirrhosis

• Ocrelizumab may be used with caution in patients with compensated liver cirrhosis who have preserved liver function 1
• Monitoring considerations for patients with compensated cirrhosis receiving ocrelizumab:
  • Regular assessment of liver function tests 2, 3
  • Monitoring of immunoglobulin levels, as decreased levels (especially IgG) are associated with increased risk of serious infections 1
  • Close observation for signs of infection, as B-cell depletion may further compromise immune function in already immunocompromised cirrhotic patients 1, 2

Contraindications in Decompensated Liver Cirrhosis

• Ocrelizumab should be avoided in patients with decompensated liver cirrhosis due to:
  • Increased risk of serious infections in an already immunocompromised population 1, 2
  • Potential for further immune dysfunction in patients with advanced liver disease 1, 3
  • Similar to interferon-α, which is contraindicated in decompensated cirrhosis due to risk of serious complications including infection and hepatic failure 5

Monitoring Recommendations

• If ocrelizumab is used in compensated cirrhosis, implement the following monitoring:
  • Baseline and periodic liver function tests 2, 4
  • Quantitative serum immunoglobulin levels before, during, and after treatment 1
  • Vigilant monitoring for signs of infection or hepatic decompensation 1, 2
  • Consider discontinuing ocrelizumab if serious opportunistic or recurrent infections occur 1
  • Monitor for signs of immune-mediated colitis, which may require prompt intervention 1

Special Considerations

• Patients with cirrhosis often have impaired renal function despite normal serum creatinine levels, which may affect drug clearance 3, 4
• The pharmacokinetics of ocrelizumab may be less predictable in cirrhotic patients due to variable hepatic metabolism and potential portosystemic shunting 2, 3
• B-cell depleting therapies like ocrelizumab may have a more pronounced effect on the already compromised immune system of cirrhotic patients 1, 2

Practical Approach

• For patients with compensated cirrhosis (Child-Pugh A):
  • Ocrelizumab may be used with careful monitoring 1
  • Consider more frequent clinical and laboratory assessments than typically recommended 2, 4
• For patients with decompensated cirrhosis (Child-Pugh B or C):
  • Avoid ocrelizumab due to increased risk of serious complications 1, 2
  • Consider alternative therapies with better established safety profiles in advanced liver disease 2, 6