The effects of leucovorin (folinic acid) on methotrexate therapy in rheumatoid arthritis patients

Arthritis Rheum. 1988 Jul;31(7):906-8. doi: 10.1002/art.1780310712.


High-dose leucovorin (folinic acid) supplementation was tested in a prospective, unblinded manner for 4 weeks in 7 rheumatoid arthritis patients who were being treated successfully with low-dose methotrexate (MTX). Nausea caused by MTX disappeared; however, the underlying rheumatic disease worsened in all patients. Subjective clinical assessment, Ritchie articular index, grip strength, erythrocyte sedimentation rate, and levels of C-reactive protein showed statistically significant deterioration. All these parameters improved after the leucovorin was stopped. This is the first direct clinical evidence implying folate antagonism in the action of low-dose MTX therapy in rheumatoid arthritis patients.

MeSH terms

  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use*
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Middle Aged


  • Leucovorin
  • Methotrexate