What tests are required before starting methotrexate (methotrexate) therapy?

Pre-Treatment Testing Requirements for Methotrexate

Before initiating methotrexate therapy, obtain complete blood count with differential, liver function tests (ALT, AST, alkaline phosphatase, albumin, bilirubin), serum creatinine, and hepatitis B and C serologic studies. 1, 2, 3

Essential Baseline Laboratory Tests

Hematologic Assessment

• Complete blood count (CBC) with differential and platelet count is required prior to starting methotrexate 1, 2
• This baseline is critical because methotrexate can cause myelosuppression, and pancytopenia can occur even after a single dose in patients with risk factors 1

Renal Function

• Serum creatinine measurement is mandatory before initiation 1, 2
• Methotrexate is eliminated almost entirely by the kidneys (85% renal excretion), making renal function assessment crucial 1, 2, 4
• For elderly patients or those with decreased muscle mass who may have normal creatinine despite reduced renal function, calculate glomerular filtration rate 1

Hepatic Assessment

• Liver function tests including ALT, AST, alkaline phosphatase, albumin, and bilirubin must be obtained 1, 2, 3
• These baseline values are essential for monitoring hepatotoxicity, which is more common in psoriasis patients than rheumatoid arthritis patients 1

Infectious Disease Screening

• Hepatitis B and C antibody testing is recommended for all patients prior to initiating methotrexate 1, 3
• This screening is particularly important because chronic hepatitis B or C infection increases the risk of hepatotoxicity 1, 3

Additional Pre-Treatment Assessments

Imaging Studies

• Chest X-ray should be obtained as part of baseline assessment 2
• This is important for detecting pre-existing pulmonary disease, as methotrexate can cause pulmonary toxicity 2

Liver Fibrosis Assessment (For Psoriasis Patients)

• Non-invasive baseline liver fibrosis assessment is recommended before starting methotrexate in psoriasis patients 1
• Baseline liver biopsy is NOT recommended regardless of risk factors 1
• For patients with risk factors for hepatotoxicity (obesity with BMI ≥40, diabetes, hyperlipidemia, greater than moderate alcohol use, persistent abnormal liver function tests, chronic hepatitis B or C, prior hepatotoxic drug exposure, or family history of inheritable liver disease), consider GI/hepatology referral or vibration-controlled transient elastography 1

Special Considerations for Rheumatoid Arthritis Patients

• Pretreatment liver biopsy should be considered ONLY for RA patients with: 3
  • History of prior excessive alcohol consumption
  • Persistently abnormal baseline AST values
  • Chronic hepatitis B or C infection

Clinical History Requirements

Critical Information to Obtain

• Alcohol intake assessment - patients should limit alcohol to well below national guidelines 1
• Medication history - identify potential drug interactions including NSAIDs, salicylates, sulfonamides, trimethoprim, and probenecid 1, 2, 5
• Reproductive planning - women must use two methods of contraception and have a pregnancy test prior to starting therapy 1
• Family history of inheritable liver disease (Wilson disease, hemochromatosis, α-1 antitrypsin deficiency) 1

Test Dose Consideration

• A test dose of 2.5-5 mg should be considered, especially in patients with impaired kidney function 1
• If no evidence of myelosuppression or hepatotoxicity occurs, the weekly dose can be increased as needed 1

Common Pitfalls to Avoid

• Do not skip hepatitis B and C screening even in patients without obvious risk factors, as these infections significantly increase hepatotoxicity risk 1, 3
• Do not rely solely on serum creatinine in elderly patients or those with low muscle mass - calculate GFR to accurately assess renal function 1
• Do not perform routine baseline liver biopsies in psoriasis patients, as this is no longer recommended practice 1
• Ensure pregnancy testing is performed in women of childbearing potential before initiating therapy 1, 2