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Monitoring methotrexate toxicity: Are we being over-vigilant?

BMJ 2023; 381 doi: (Published 30 May 2023) Cite this as: BMJ 2023;381:p1120

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Risk stratified monitoring for methotrexate toxicity in immune mediated inflammatory diseases: prognostic model development and

  1. Prabha Ranganathan, professor of medicine
  1. Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
  1. pranganathan{at}

Prediction model could help identify patients needing more or less frequent monitoring

Despite the advent of new disease modifying antirheumatic drugs in the past 20 years, low dose methotrexate remains the first line treatment for inflammatory conditions such as rheumatoid arthritis and psoriatic arthritis. This is because of its long record of efficacy and safety spanning almost four decades.1 Despite the established safety of methotrexate, about 20-30% of patients discontinue treatment because of side effects.2 Common nuisance side effects are nausea, vomiting, mild mucositis, and hair loss, but major side effects such as cytopenias and abnormal liver enzyme levels (usually raised serum aspartate transaminase and/or alanine transaminase, or transaminitis) can occur, requiring a decrease in methotrexate dose or discontinuation of the drug. Although methotrexate does not affect kidney function in itself, impaired renal function can increase the risk for toxicity. Abnormalities in blood counts, liver enzyme levels, and renal function are often detected on laboratory testing in the absence of attributable symptoms. For this reason, all patients taking methotrexate …

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