Pre-Treatment Testing Before Starting Methotrexate

Essential Laboratory Tests

The American College of Rheumatology recommends obtaining complete blood count with differential, liver function tests, serum creatinine, hepatitis B and C serologies, and a chest X-ray before initiating methotrexate therapy 1
Complete blood count (CBC) with differential and platelet count is mandatory to assess baseline bone marrow function and risk of myelosuppression, which typically occurs early in treatment (first 4-6 weeks) and accounts for the majority of methotrexate-associated fatalities 2
Serum creatinine measurement is required because methotrexate is eliminated almost entirely by the kidneys, and renal insufficiency is a primary risk factor for methotrexate toxicity due to impaired drug clearance 1
Liver function tests including ALT, AST, alkaline phosphatase, albumin, and bilirubin must be obtained to establish baseline hepatic function, which is essential for monitoring hepatotoxicity, a major concern with methotrexate therapy 1, 3

The American College of Rheumatology recommends hepatitis B and C serologic studies for all patients prior to initiating methotrexate, regardless of apparent risk factors, as undiagnosed hepatitis significantly increases the risk of hepatotoxicity 1
HIV serology should be considered based on individual circumstances and local epidemiology 2, 3

A chest X-ray (obtained within the previous year) is required to establish baseline pulmonary status, as pulmonary fibrosis accounts for a significant proportion of methotrexate-associated fatalities 1

Non-invasive baseline liver fibrosis assessment is recommended before starting methotrexate in psoriasis patients, particularly those with BMI >28 kg/m² or alcohol intake >14 drinks per week 4, 5
Baseline liver biopsy is NOT recommended, regardless of risk factors, as routine liver biopsies are no longer considered necessary 3, 4, 5
The European League Against Rheumatism recommends documenting alcohol intake, as patients should limit consumption to well below national guidelines, and excessive alcohol consumption is a major risk factor for hepatotoxicity 3, 5
A comprehensive medication history should be obtained to identify potential drug interactions, particularly NSAIDs, salicylates, sulfonamides, trimethoprim-sulfamethoxazole, penicillins, and probenecid 4
Pregnancy testing must be performed in women of childbearing potential before initiating therapy, and both male and female patients should be counseled about the need for effective contraception, as methotrexate is pregnancy category X 4, 2, 3

A test dose of 2.5-5 mg (or 1.25-5 mg in pediatric patients) should be considered, especially in patients with impaired kidney function, followed by a complete blood count 5 or 6 days later to check for acute idiosyncratic bone marrow toxicity 2, 4

The American College of Rheumatology strongly recommends monitoring CBC, liver function tests, and renal function tests within the first 1-2 months of starting methotrexate and every 3-4 months thereafter 6
Laboratory tests should be performed at least 4-6 days after methotrexate dosing to avoid making dosage adjustments based on transient elevations of hepatic transaminases 7, 8
Avoid liver function tests within 2 days after methotrexate dose as transient elevations may occur 6
HIV serology should be considered based on individual circumstances and local epidemiology 7
Monitoring for latent tuberculosis should be considered before therapy based on individual circumstances and local epidemiology 7
An initial test dose of 2.5-5 mg (or 1.25-5 mg in pediatric patients) should be considered, especially in patients with impaired kidney function, followed by a CBC 5-6 days later to detect acute idiosyncratic bone marrow toxicity 8
Use of folic/folinic acid in conjunction with methotrexate is strongly recommended to mitigate adverse events and improve tolerability, typically 1 mg daily (or 6 days per week, sparing the day of methotrexate administration) 6, 8