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

Objective To investigate the efficacy of folinic acid in reducing the side effects as sociated with methotrexate (MTX) therapy in children with juvenile idiopath ic arthritis (JIA) and to determine whether folate supplementation may redu ce 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/m(2)/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 p atients were started on folinic acid only after the development of a side e ffect. Exclusion criteria were: treatment with higher doses of MTX (> 20 mg /m(2)/week). The outcomes investigated were: hepatotoxicity (liver transami nase increase), gastrointestinal toxicity, disease flare, and clinical remi ssion. The number of episodes per patient-year of MTX treatment of each out come before and after folinic acid supplementation was compared by the Wilc oxon matched pairs test. Results A total of 43 children with JIA were included in the study. The mean durati on of treatment before and after folinic acid supplementation was 1.1 years and 1.8 years, respectively. After the start of folinic acid supplementati on, the mean number of episodes per patient-year of hepatotoxicity and gast rointestinal 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 c linical 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 cl inical efficacy of the drug.