What are the management options for a patient with a downward trend in albumin levels while on methotrexate (disease-modifying antirheumatic drug, DMARD)?

From the Guidelines

Temporarily discontinuing methotrexate and arranging for comprehensive liver function testing is crucial in managing a patient with a downward trend in albumin levels while on methotrexate. This approach is supported by the guidelines of care for the management of psoriasis and psoriatic arthritis, which recommend careful monitoring of liver function tests, including alanine aminotransferase, AST, alkaline phosphatase, and serum albumin levels, every 4 weeks 1. Hypoalbuminemia during methotrexate therapy may indicate hepatotoxicity, which can progress to fibrosis or cirrhosis if not addressed.

Key Considerations

• Consider ordering an abdominal ultrasound to assess for liver abnormalities and consult with gastroenterology for possible liver biopsy if liver enzymes are significantly elevated.
• Alternative DMARDs such as leflunomide (20mg daily), hydroxychloroquine (200-400mg daily), or sulfasalazine (2-3g daily) should be considered to maintain disease control, as recommended by multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders 1.
• Biologics like TNF inhibitors may also be appropriate depending on the underlying condition.
• Monitor nutritional status as hypoalbuminemia can reflect poor nutrition, and supplement with protein if needed.

Methotrexate Reintroduction

Once albumin levels normalize and liver function improves, methotrexate may be cautiously reintroduced at a lower dose (5-7.5mg weekly) with close monitoring, or permanently discontinued if liver damage is confirmed, in line with the recommendations for methotrexate use in rheumatoid arthritis and other rheumatic disorders 1. Regular liver function monitoring (every 4-8 weeks) is essential for any patient on DMARDs.

From the FDA Drug Label

Persistent liver function test abnormalities, and/or depression of serum albumin may be indicators of serious liver toxicity and require evaluation

The management options for a patient with a downward trend in albumin levels while on methotrexate include:

• Reducing the dosage of methotrexate or discontinuing it
• Implementing appropriate corrective measures, such as the use of leucovorin calcium
• Close monitoring of the patient for signs of toxicity and adjusting the treatment plan as needed 2
• Evaluation for possible liver toxicity, as depression of serum albumin may be an indicator of serious liver toxicity 2
• Considering alternative treatments or adjusting the dosage regimen to minimize the risk of liver toxicity and albumin depression 2

From the Research

Management Options for Downward Trend in Albumin Levels

• Monitor liver function tests, including albumin levels, every 4-8 weeks while on methotrexate 3
• Consider liver biopsy if a patient develops persistent abnormalities on liver blood tests, including a decrease in serum albumin below the normal range 3
• Assess for risk factors for liver disease, such as prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection 3

Predictors of Liver Enzyme Elevation

• Pre-treatment elevation of ALT is a strong predictor of ALT elevation during methotrexate therapy 4
• Other factors, such as MTX dose and duration of treatment, may also contribute to liver enzyme elevation 5

Handling of Elevated Liver Enzymes

• Recurrent elevations of ALT may occur in patients who continue methotrexate treatment, despite interventions such as dose reduction 4
• Permanent discontinuation of methotrexate due to ALT elevation is rare, and alternative treatments may be considered 4

Surveillance and Outcome

• Long-term follow-up of patients on methotrexate is necessary to monitor for liver enzyme elevation and other potential side effects 4
• Individualized approach to monitoring and handling of ALT elevations during methotrexate therapy may be necessary, rather than following strict guidelines 4