Parenteral Methotrexate Intolerance is High in Juvenile Idiopathic Arthritis Save

Juvenile idiopathic arthritis (JIA) is commonly managed with methotrexate (MTX), with many pediatric rheumatologists preferring to use parenteral MTX for compliance and absorption reasons.

A cross-sectional study of 179 JIA patients on MTX was performed to examine the relationship between dosing and MTX intolerance (using the validated Methotrexate Intolerance Severity Score questionnaire).

Of the JIA patients on MTX, 73 (40.8%) were intolerant. MTX intolerance was higher with parenteral MTX compared to orally administered (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]).

There was strong evidence that the former experienced more behavioural/CNS complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056).

It is well-known that MTX toxicity is directly related to drug levels. Since higher levels (and presumed efficacy) is better achieved with parenteral administration, it's not surprising higher toxicity was also observed. The frequently held assumption that SC causes fewer side effects than PO is unwarranted and questions whether oral doses or split oral doses may be an alternative means of improving the tolerability of MTX. 

(Editor's note:  please see our previous article on managing/improving MTX toxicity)