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van Ede, A.E., Laan, R.F., Rood, M.J., Huizinga, T.W., van de Laar, M.A., van Denderen, C.J., Westgeest, T.A., Romme, T.C., de Rooij, D.J., Jacobs, M.J., de Boo, T.M., van der Wilt, G.J., Severens, J.L., Hartman, M., Krabbe, P.F., Dijkmans, B.A., Breedveld, F.C. and van de Putte, L.B. (2001) Effect of Folic or Folinic Acid Supplementation on the toxicity and Efficacy of methotrexate in Rheumatoid Arthritis: A Forty-Eight Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Arthritis & Rheumatology, 44, 1515-1224.
https://doi.org/10.1002/1529-0131(200107)44:7<1515::AID-ART273>3.0.CO;2-7

has been cited by the following article:

• TITLE: Efficacy of Folinic Acid in Comparison to Folic Acid for Reducing Side Effects of Methotrexate in Children with Juvenile Idiopathic Arthritis

  AUTHORS: Sazida Islam, Mohammad Zahirul Islam Khan, Kamrul Laila, Mohammed Mahbubul Islam, Shahana A. Rahman

  KEYWORDS: Folinic Acid, Folic Acid, Adverse Events, Disease Activity

  JOURNAL NAME: Open Journal of Pediatrics, Vol.13 No.2, March 2, 2023

  ABSTRACT: Background: Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. Several patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX-induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX. Objectives: To assess the efficacy of folinic acid in comparison to folic acid for reducing the side effects of MTX in JIA patients. Material and methods: In this prospective observational study, newly diagnosed cases of JIA who would be getting MTX were included by purposive sampling. Data were collected using a predesigned questionnaire. Among 40 patients, 20 received folinic acid (Group A), and 20 received folic acid (Group B). Disease activity levels were assessed by JADAS-27 (Juvenile Arthritis Disease Activity Score). Contents from the MISS (MTX Intolerance severity score) questionnaire were used to assess the side effects. All patients were evaluated at baseline, 6th, and 12th weeks. Results: There were significant differences in the frequency of MTX-related adverse events between folinic acid (Group A) and folic acid (Group B). Group A patients only had nausea (10% and 15% in the 6th & 12th week respectively) and vomiting (5% at both follow-ups). On the other hand, in addition to nausea (70% and 95% in the 6th & 12th week) and vomiting (20% and 90% in the 6th & 12th week), folic acid group patients had restlessness, crying, and irritability. Self-discontinuation of MTX was present in the folic acid group (5% & 10% in the 6th & 12th week). Improvement of disease activity was more in the folinic acid group. Conclusion: The folinic acid group had significantly fewer side effects. Improvement of disease activity was more and compliance was also better among them. Methotrexate (MTX) is the most effective and commonly used disease-modifying anti-rheumatic drug in the management of juvenile idiopathic arthritis. A number of patients develop side effects, which may lead to low quality of life and non-compliance to MTX. To reduce MTX induced side effects, folic acid supplementation is prescribed by most rheumatologists. Even after that, some patients have symptoms while receiving MTX.