Abstract

ObjectivesTo analyse the internal consistency of an adaption of the methotrexate intolerance severity score (MISS); and to describe and compare the level of methotrexate intolerance evaluated by the MISS in Danish children with juvenile idiopathic arthritis (JIA) or acute lymphoblastic leukaemia (ALL), treated with low-dose methotrexate (MTX).MethodsCross-sectional study of children diagnosed with JIA or ALL, treated with low-dose MTX, aged 9 years or above, and cognitively intact. The patient’s parents completed the MISS. MTX intolerance was defined as a total MISS score above 6.ResultsWe enrolled 120 children with JIA and 23 children with ALL. The MISS had a good internal consistency in the JIA group. The median MISS score was higher in the JIA group than in the ALL group (JIA: 8; ALL: 1; p<0.0001); and the JIA group had a larger proportion of MTX intolerant children than the ALL group (JIA: 73/120; ALL: 4/23; p<0.001). Within both the JIA group and the ALL group, the MISS total score was not significantly correlated with age, MTX dose or the duration of low-dose MTX treatment.ConclusionIn the JIA group the level of MTX intolerance was higher and more attributed to anticipatory, associative and behavioural symptoms than in the ALL group. The MISS may help to uncover whether MTX intolerance is present and which aspects are affected in the individual patient, thus guiding intervention. The MISS may also be applicable within leukaemia care.

Highlights

  • Low-dose methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA) with polyarticular involvement [1–3] and in the maintenance treatment of acute lymphoblastic leukaemia (ALL) in combination with 6-mercaptopurine [4].Gastrointestinal adverse effects, including anticipatory and associative symptoms, are described to be a significant clinical challenge to low-dose MTX treatment in JIA [5–7]

  • The methotrexate intolerance severity score (MISS) may help to uncover whether MTX intolerance is present and which aspects are affected in the individual patient, guiding intervention

  • The MISS may be applicable within leukaemia care

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Summary

Introduction

Gastrointestinal adverse effects, including anticipatory and associative symptoms, are described to be a significant clinical challenge to low-dose MTX treatment in JIA [5–7]. With the increasing survival rates of children with ALL [8–10] the role of adverse effects related to the maintenance treatment has gained higher significance, but there are few studies focusing on low-dose MTX. Tools quantifying gastrointestinal adverse effects to low-dose MTX are crucial for identification and monitoring affected patients in order to assist patients in maintaining a superior health-related quality of life [11] and adhering to therapy. The methotrexate intolerance severity score (MISS) has been developed in a Dutch JIA cohort as a quantitative measure of the low-dose MTX-associated gastrointestinal adverse effects and incorporates anticipatory, associative, and behavioural complaints [6]. Important lessons may be learnt regarding MTX intolerance through the analysis and comparison of two disease entities using the same tool

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