Hepatotoxicity Risks Associated with Anakinra and Monitoring Recommendations
Anakinra carries a risk of hepatotoxicity that requires regular monitoring of liver function tests, particularly during the first 1-2 months of treatment and every 3-4 months thereafter. 1
Hepatotoxicity Risk Profile
- Elevations of transaminases have been identified as a post-marketing adverse reaction with anakinra, though the frequency cannot be reliably estimated due to voluntary reporting 2
- Non-infectious hepatitis has also been reported as a post-marketing adverse event with anakinra 2
- Liver function test abnormalities are among the most common adverse events reported in clinical practice with anakinra 3
- Severe cases of hepatotoxicity have been documented, including acute liver failure in adolescent patients with Still's disease 4
- Liver biopsy in patients with anakinra-induced hepatotoxicity has shown focal necrosis of hepatocytes, steatosis, early fibrosis, and inflammatory infiltrates - hallmarks of drug toxicity 5, 6
Monitoring Recommendations
- Baseline liver function tests should be performed before initiating anakinra therapy 1
- Monitor liver function tests within the first 1-2 months of anakinra usage 1
- Continue monitoring every 3-4 months thereafter for the duration of treatment 1
- More frequent monitoring may be necessary in patients with pre-existing liver disease or those taking other potentially hepatotoxic medications 7
- Abnormal LFT elevations should prompt repeat laboratory checks in 2-4 weeks 1
- For persistent elevations, referral to a gastroenterologist is recommended 1
Management of Hepatotoxicity
- If significant liver injury is detected, immediate discontinuation of anakinra should be considered 7
- Withdrawal of anakinra typically leads to rapid normalization of liver function in cases of drug-induced hepatotoxicity 5, 6
- Perform thorough evaluation to rule out other causes of liver injury when hepatotoxicity is suspected 7
- Consider dose reduction or temporary discontinuation for moderate elevations in liver enzymes 7
Risk Factors for Hepatotoxicity
- Patients with pre-existing liver disease require more careful monitoring 7
- Concurrent use of other hepatotoxic medications may increase the risk of liver injury 7
- Obesity, diabetes, and hyperlipidemia are general risk factors that may increase susceptibility to drug-induced liver injury 7
- In patients with COVID-19 treated with anakinra, liver function abnormalities were among the most common adverse events 3
Special Considerations
- In a study of patients with secondary hemophagocytic lymphohistiocytosis (HLH) treated with anakinra, one patient experienced grade 3 liver injury 8
- The risk of hepatotoxicity must be balanced against the potential benefits of anakinra, especially in conditions with limited treatment options 5
- When using anakinra for systemic inflammatory conditions, the decision to continue or discontinue treatment in the presence of mild liver enzyme elevations should be based on the overall clinical picture and response to therapy 5, 6
- For patients with rheumatologic causes of inflammatory conditions, anakinra appears to have a more favorable risk-benefit profile compared to those with other underlying conditions 8
Anakinra-induced hepatotoxicity is a recognized adverse effect that requires vigilant monitoring. While severe cases including acute liver failure have been reported, most cases of liver enzyme elevations are mild to moderate and resolve with dose adjustment or discontinuation of the medication.