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Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients

Lisa K Stamp1, John L O'Donnell, Peter T Chapman

  • 1University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz

Arthritis and Rheumatism
|January 30, 2010
PubMed
Abstract

Insights

Methotrexate polyglutamate (MTXGlu) levels in red blood cells did not correlate with disease activity or adverse effects in rheumatoid arthritis patients. Red blood cell folate levels may be more influential for disease control in long-term oral MTX therapy.

Area of Science:

  • Rheumatology
  • Pharmacology
  • Clinical Chemistry

Background:

  • Limited data exist on using methotrexate polyglutamate (MTXGlu) concentrations to guide methotrexate (MTX) dosing in rheumatoid arthritis (RA).
  • Understanding the relationship between MTXGlu levels, disease activity, and adverse effects is crucial for optimizing long-term MTX therapy.

Purpose of the Study:

  • To define a therapeutic range for red blood cell (RBC) MTXGlu(n) concentrations in patients with RA on long-term oral MTX.
  • To identify threshold values for efficacy and adverse effects related to MTXGlu(n) levels.

Main Methods:

  • A cross-sectional study involving 192 patients receiving oral MTX.
  • Disease activity assessed using swollen/tender joint counts, C-reactive protein, and Disease Activity Score in 28 joints (DAS28).
  • Standardized questionnaire for MTX adverse effects.

Main Results:

  • Higher MTX dosage correlated with higher swollen joint count and DAS28.
  • Elevated MTXGlu(4), MTXGlu(5), MTXGlu(3-5), and MTXGlu(1-5) concentrations were observed in patients with high disease activity, with MTXGlu(5) remaining significant after adjustments.
  • Higher RBC folate concentrations were found in the high disease activity group; no association between MTXGlu(n) and adverse effects was found.

Conclusions:

  • This study did not find a relationship between MTXGlu(n) concentration and reduced disease activity in RA patients on long-term MTX.
  • RBC folate levels may play a more significant role in disease control than MTXGlu(n) concentrations.
  • Further prospective studies are needed to clarify the role of measuring MTXGlu(n) concentrations in long-term MTX treatment for RA.

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