Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid arthritis

J Rheumatol. 2006 Jul;33(7):1275-81.


Objective: Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake.

Methods: Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment.

Results: Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant.

Conclusion: Caffeine intake among patients taking high doses of MTX for RA did not affect MTX efficacy and RA disease activity over time.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / physiopathology
  • Caffeine / administration & dosage*
  • Caffeine / pharmacokinetics
  • Central Nervous System Stimulants / administration & dosage*
  • Central Nervous System Stimulants / pharmacokinetics
  • Cohort Studies
  • Diet
  • Drug Interactions
  • Female
  • Health Status
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prospective Studies
  • Severity of Illness Index
  • Surveys and Questionnaires


  • Antirheumatic Agents
  • Central Nervous System Stimulants
  • Caffeine
  • Methotrexate