How to manage elevated liver enzymes in a patient taking Rinvoq (upadacitinib) and diclofenac?

Management of Elevated Liver Enzymes in a Patient on Rinvoq and Diclofenac

The patient should immediately discontinue diclofenac and have liver enzymes rechecked in 1-2 weeks while continuing Rinvoq with close monitoring. 1, 2

Assessment of Current Situation

The patient presents with:

• ALT 147 (>3x upper limit of normal)
• AST 74 (approximately 2x upper limit of normal)
• Current medications: Rinvoq (upadacitinib) 15mg and diclofenac 75mg

Management Algorithm

Step 1: Identify the Likely Cause

• Diclofenac is the most probable cause of liver enzyme elevation

  • Diclofenac has higher rates of hepatic injury compared to other NSAIDs 1
  • In a large study of 17,289 patients, 3.1% of patients on diclofenac developed ALT/AST >3x ULN 3
  • Liver enzyme elevations with diclofenac typically occur within the first 4-6 months of therapy 3

• Rinvoq (upadacitinib) can also cause liver enzyme elevations

  • FDA label notes that "treatment with RINVOQ was associated with increased incidence of liver enzyme elevations" 2
  • However, NSAIDs, particularly diclofenac, have a stronger association with hepatotoxicity

Step 2: Immediate Actions

1. Discontinue diclofenac - This is the most likely hepatotoxic agent 1, 3
2. Continue monitoring Rinvoq - Do not immediately discontinue as the evidence suggests diclofenac is more likely the culprit
3. Recheck liver enzymes in 1-2 weeks - To assess if discontinuing diclofenac resolves the issue 1

Step 3: Follow-up Based on Repeat Testing

• If liver enzymes improve or normalize:

  • Continue without diclofenac
  • Consider alternative pain management options (acetaminophen, topical agents, or different class of analgesics)
  • Monitor liver enzymes monthly for 3 months to ensure continued normalization

• If liver enzymes remain elevated >3x ULN or worsen:

  • Temporarily withhold Rinvoq 2
  • Consider hepatology consultation 1
  • Investigate for other causes of liver enzyme elevation (viral hepatitis, alcohol use, other medications)
  • Once enzymes improve to <3x ULN, consider restarting Rinvoq at the same or reduced dose with close monitoring

Evidence-Based Rationale

1. Diclofenac has higher hepatotoxicity risk:

   • According to the American Family Physician guidelines, "some NSAIDs, particularly sulindac and diclofenac, showed higher rates of hepatic injury and transaminase elevation more than three times the upper limit of normal compared with placebo" 1
   • A large prospective trial found diclofenac associated with ALT/AST >3x ULN in 3.1% of patients 3

2. Management of NSAID-induced liver injury:

   • The American College of Rheumatology recommends discontinuing NSAIDs when liver enzymes are elevated 1
   • For liver enzyme elevation >2x ULN, decreasing the dose or temporarily withholding medication is recommended 1
   • For liver enzymes >3x ULN, discontinuation is recommended 1

3. Rinvoq monitoring and management:

   • FDA label for Rinvoq states: "If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded" 2
   • Since diclofenac is more likely the cause, Rinvoq can be continued with close monitoring initially

Common Pitfalls to Avoid

1. Failing to recognize diclofenac as a common cause of hepatotoxicity

   • Diclofenac is associated with liver injury more frequently than other NSAIDs 1, 3

2. Discontinuing all medications simultaneously

   • This prevents identification of the specific causative agent
   • A stepwise approach starting with the most likely culprit (diclofenac) is preferred

3. Inadequate follow-up monitoring

   • Liver enzymes should be rechecked within 1-2 weeks after medication changes
   • Regular monitoring should continue until normalization

4. Missing other potential causes

   • Consider viral hepatitis, alcohol use, and other medications if liver enzymes don't improve after diclofenac discontinuation

By following this approach, you can effectively manage the elevated liver enzymes while maintaining necessary treatment for the patient's underlying condition that requires Rinvoq therapy.