Folate usage in MTX-treated juvenile idiopathic arthritis (JIA) patients is inconsistent and highly variable

Abstract

Folate supplementation is widely accepted and utilized for the prevention of adverse events in juvenile idiopathic arthritis (JIA) patients who are treated with methotrexate. Despite the widespread use of folate supplementation, there is a lack of convincing evidence to support the role of folate in the enhancement of methotrexate efficacy and the prevention of methotrexate-related adverse events. In order to understand current practices used by experts, we surveyed 214 pediatric rheumatologists around the globe. Seventy-one unique folate supplementation regimens were reported for this study. Results indicated that folate supplementation (either in the form of folic acid or folinic acid) is inconsistent and highly variable within the United States as well as between the United States and other countries. This level of variability is often associated with lack of evidence and emphasizes the need for well-designed clinical trials to support a rational folate supplementation regimen in patients with JIA who are treated with methotrexate.

Methotrexate in pediatric plaque-type psoriasis: Long-term daily clinical practice results from the Child-CAPTURE registry

“…Nausea was already reported in the available literature on MTX in pediatric psoriasis (4)(5)(6), and also in other indications in children nausea is a wellknown side-effect (29,30). Possibly, different treatment schedules in folic acid administration can influence the presence of nausea and other AEs; the effect of different treatment schedules of folic acid administration on the effectiveness and side effects in MTX therapy is still subject of debate (8,31) and the use and dose regimen of folic acid administration is highly variable (32). In the pediatric psoriasis literature, tiredness was not reported until now, whereas in this study, it was reported as reason for discontinuation.…”

Strategic use of levofolinic acid for methotrexate-induced side effects in juvenile idiopathic arthritis: a prospective observational study

“…Our data show that higher dosage of folates may be beneficial in patients with MTX-related GI complaints and also the route of administration may be important, as in our patients the strategy of giving LVF before MTX might have contributed to effectiveness. Indeed, the optimal folate regimen is still matter of debate and there is great variability among clinicians on prevention and treatment of MTX-related side effects [ 9 , 20 ]. Therefore, further studies using LVF or FA before MTX since the start of the treatment should be performed to evaluate if this modality is effective also in preventing the development of adverse effects.…”

A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology

“…However, Arabelovic and associates' preliminary study showed a significant increase of MTX dose needed [ 114 ], since folic acid fortification enriched cereal grain products were fully implemented in the USA and Canada [ 115 ]. This conveyed a message to us that high dose of folate supplementation might have influence on the efficacy of MTX.…”