Efficacy of folinic acid in reducing methotrexate toxicity in juvenile idiopathic arthritis

Clin Exp Rheumatol. Sep-Oct 1999;17(5):625-7.


Objective: To investigate the efficacy of folinic acid in reducing the side effects associated with methotrexate (MTX) therapy in children with juvenile idiopathic arthritis (JIA) and to determine whether folate supplementation may reduce the benefit of MTX administration.

Methods: This was a retrospective, non-controlled study. Inclusion criteria were: 1) diagnosis of JIA according to the Durban 1997 criteria; 2) treatment with low to intermediate doses of MTX (10-20 mg/m2/week) as the sole second-line agent for at least 6 mos.; and 3) supplementation with folinic acid (2.5-7.5 mg) in a single weekly dose 24 hrs after MTX administration. All patients were started on folinic acid only after the development of a side effect. Exclusion criteria were: treatment with higher doses of MTX (> 20 mg/m2/week). The outcomes investigated were: hepatotoxicity (liver transaminase increase), gastrointestinal toxicity, disease flare, and clinical remission. The number of episodes per patient-year of MTX treatment of each outcome before and after folinic acid supplementation was compared by the Wilcoxon matched pairs test.

Results: A total of 43 children with JIA were included in the study. The mean duration of treatment before and after folinic acid supplementation was 1.1 years and 1.8 years, respectively. After the start of folinic acid supplementation, the mean number of episodes per patient-year of hepatotoxicity and gastrointestinal toxicity decreased from 2.30 to 0.32 (p < 0.001) and from 1.09 to 0.29 (p = 0.002), respectively. The mean number of disease flares and clinical remissions per patient-year did not change significantly.

Conclusion: In our JIA patients, folinic acid supplementation resulted in a significant reduction in the most common side effects of MTX, without affecting the clinical efficacy of the drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antirheumatic Agents / toxicity*
  • Arthritis, Juvenile / drug therapy*
  • Child
  • Child, Preschool
  • Female
  • Folic Acid Antagonists / toxicity*
  • Humans
  • Infant
  • Leucovorin / administration & dosage*
  • Male
  • Methotrexate / toxicity*
  • Retrospective Studies
  • Treatment Outcome


  • Antirheumatic Agents
  • Folic Acid Antagonists
  • Leucovorin
  • Methotrexate