What are the treatment options for Rheumatoid Arthritis (RA) in patients with Liver Failure?

From the Guidelines

Rheumatoid arthritis treatment in patients with liver failure should prioritize medications with a safer liver profile, such as hydroxychloroquine and low-dose corticosteroids, while avoiding traditional DMARDs like methotrexate and leflunomide due to their potential for liver toxicity 1. When managing rheumatoid arthritis in the context of liver failure, it's crucial to consider the potential hepatotoxic effects of various medications.

Key Considerations

• Non-pharmacological approaches, including physical therapy and occupational therapy, should be emphasized to reduce the reliance on medications.
• Medications like hydroxychloroquine are considered safer for the liver and can be used at standard doses.
• Low-dose corticosteroids can help control inflammation but should be used judiciously due to their potential side effects.
• Traditional DMARDs, such as methotrexate and leflunomide, are generally contraindicated in liver failure due to their hepatotoxic potential, as highlighted in the EULAR recommendations for the management of rheumatoid arthritis 1.

Medication Selection

• Hydroxychloroquine may be used at standard doses (200-400 mg daily) as it is generally considered safer for the liver.
• Low-dose corticosteroids, like prednisone (5-10 mg daily), can be used to control inflammation during flares but should be tapered as rapidly as clinically feasible, in line with recommendation 6 from the EULAR guidelines 1.
• Biologic agents, particularly IL-6 inhibitors like tocilizumab or TNF inhibitors like etanercept, may be considered for moderate to severe RA in liver failure patients, with careful dose adjustments and monitoring, as suggested by the EULAR recommendations for the use of bDMARDs and tsDMARDs 1.

Monitoring and Multidisciplinary Approach

• Regular liver function testing is essential, typically every 2-4 weeks initially and then every 1-3 months once stable.
• Patients should be monitored for signs of liver decompensation.
• A multidisciplinary approach involving rheumatologists, hepatologists, and pharmacists is ideal to balance RA treatment while preserving remaining liver function, aligning with the principles of treating toward a target of remission or low disease activity as outlined in the EULAR recommendations 1.

From the FDA Drug Label

Hepatic Methotrexate has the potential for acute (elevated transaminases) and chronic (fibrosis and cirrhosis) hepatotoxicity. Special caution is indicated in the presence of preexisting liver damage or impaired hepatic function. Pretreatment liver biopsy should be performed for patients with a history of excessive alcohol consumption, persistently abnormal baseline liver function test values or chronic hepatitis B or C infection Liver function tests should be performed at baseline and at 4 to 8 week intervals in patients receiving methotrexate for rheumatoid arthritis

Rheumatoid Arthritis Treatment in Liver Failure:

• Methotrexate is not recommended for patients with liver failure due to its potential for hepatotoxicity.
• Patients with preexisting liver damage or impaired hepatic function should be treated with caution.
• Liver function tests should be performed regularly to monitor for potential hepatotoxicity.
• Pretreatment liver biopsy is recommended for patients with a history of excessive alcohol consumption, persistently abnormal baseline liver function test values, or chronic hepatitis B or C infection.
• No information is available on the use of leflunomide in patients with liver failure. 2

From the Research

Rheumatoid Arthritis Treatment in Liver Failure

• Rheumatoid arthritis (RA) patients with liver damage may experience difficulty in determining whether the damage is a hepatic manifestation of RA, associated primary liver disease, or hepatotoxic liver disease developed during RA treatment 3.
• Liver damage in RA patients can progress to cirrhosis, and patients with RA are more susceptible to associated autoimmune liver disease 3.
• Medications used in rheumatology, such as methotrexate and leflunomide, can be hepatotoxic, making it challenging to differentiate between hepatic manifestations of the primary disease and potential hepatotoxicity of the administered medications 3, 4.

Hepatotoxicity of RA Medications

• The combination of methotrexate and leflunomide is associated with a greater risk of elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes compared to monotherapy 4.
• Non-steroidal anti-inflammatory drugs and methotrexate are commonly involved in the genesis of hepatotoxicity in RA patients 5.
• Methotrexate-related drug reactions can affect both the kidneys and liver in RA patients, with liver dysfunction reported nearly three times more often than renal impairment 6.

Clinical Features and Immune Mechanisms

• RA patients have an increased risk of suffering from liver disease independent of obesity or type 2 diabetes mellitus (T2DM) 7.
• The risk of liver disease in RA patients is associated with factors such as insulin resistance, autoantibodies, inflammation, and component C3 7.
• Methotrexate treatment can be associated with liver abnormalities in newly diagnosed RA patients with cardiovascular risk factors 7.
• Anti-citrullinated protein antibodies (ACPAs) can induce defective hepatocyte function, promoting insulin resistance and inflammation 7.