From the Guidelines
Methotrexate monitoring should include complete blood count (CBC), liver function tests (LFTs), and renal function tests, with the frequency of monitoring depending on the patient's risk factors and stability of the dose, as recommended by the most recent guidelines 1. When starting methotrexate or increasing the dose, ALT with or without AST, creatinine, and CBC should be performed every 1–1.5 months until a stable dose is reached and every 1–3 months thereafter, according to the 2009 multinational evidence-based recommendations 2. However, the 2020 joint American Academy of Dermatology-National Psoriasis Foundation guidelines recommend regular laboratory monitoring (CBC and liver function tests) every 3 to 6 months, assuming no abnormalities in laboratory test results, with periodic renal monitoring considered in patients with poor renal function 1. Key factors to consider when monitoring methotrexate include:
- Baseline CBC, LFTs, renal function, hepatitis B and C screening, and chest X-ray before starting treatment
- More frequent monitoring for patients with risk factors such as advanced age, renal impairment, or concomitant use of other hepatotoxic or nephrotoxic medications
- Close laboratory monitoring after each methotrexate dose increase, as pancytopenia can occur as late as 6 weeks 1
- Noninvasive baseline liver fibrosis assessment before starting treatment with methotrexate, with annual GI/hepatology referral or vibration-controlled transient elastography, or both, if methotrexate is continued despite abnormal baseline liver fibrosis laboratory results 1.
From the FDA Drug Label
Patients undergoing methotrexate therapy should be closely monitored so that toxic effects are detected promptly. Baseline assessment should include a complete blood count with differential and platelet counts, hepatic enzymes, renal function tests and a chest X-ray During therapy of rheumatoid arthritis and psoriasis, monitoring of these parameters is recommended: hematology at least monthly, renal function and liver function every 1 to 2 months.
The labs to monitor for methotrexate include:
- Complete blood count (CBC) with differential and platelet counts: at least monthly
- Hepatic enzymes: every 1 to 2 months
- Renal function tests: every 1 to 2 months
- Chest X-ray: at baseline Additionally, liver function tests should be performed at baseline and at 4 to 8 week intervals in patients receiving methotrexate for rheumatoid arthritis 3. Liver biopsy should be performed if there are persistent liver function test abnormalities or there is a decrease in serum albumin below the normal range (in the setting of well controlled rheumatoid arthritis) 4.
From the Research
Monitoring for Methotrexate
The following labs are monitored for patients on methotrexate:
- Full blood cell count
- Serum transaminase levels
- Serum creatinine with computation of creatinine clearance
- Chest radiograph
- Serological tests for hepatitis viruses B and C
- Serum albumin assay
- Lung function tests with determination of the diffusing capacity for carbon monoxide (in patients with a history of respiratory disease or current respiratory symptoms) 5
Frequency of Monitoring
These tests should be obtained:
- At least once a month for the first 3 months
- Every 4-12 weeks thereafter 5 Additionally, the following parameters may be used to evaluate the success of methotrexate administration:
- Neutrophil-to-lymphocyte ratio (NLR)
- Platelet distribution width (PDW)
- Platelet count (PLT) 6
Risk Factors for Abnormal Laboratory Results
The following are risk factors for methotrexate-induced abnormal laboratory results:
- Lack of folate supplementation
- Untreated hyperlipidemia
- Elevated body mass index (BMI)
- Hypoalbuminemia 7 These risk factors can increase the likelihood of abnormal laboratory results, such as elevated AST values and thrombocytopenia.