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P407 Prevalence of methotrexate intolerance in pediatric inflammatory bowel disease

C. Dupont-Lucas1, C. Grandjean-Blanchet*1, C. Larocque1, P. Jantchou1, 2, D. Amre1, 2, C. Deslandres1

1CHU Sainte Justine, Pediatric gastroenterology, Montreal, Canada, 2Saint Justine Medical Center, Research Institute, Montreal, Canada


Methotrexate (MTX) intolerance is defined as gastrointestinal and behavioural symptoms occurring before (anticipatory/associative) or after MTX administration that could lead to treatment discontinuation. Although a common complication of the drug, its prevalence is difficult to assess probably due to the subjective nature of the symptoms. A Methotrexate Intolerance Severity Score (MISS) questionnaire developed in rheumatology has shown a prevalence of MTX intolerance of 50.5% for children with juvenile idiopathic arthritis. In children with inflammatory bowel disease (IBD), the exact prevalence of MTX intolerance has never been evaluated. The aim of this study was to determine the prevalence of MTX intolerance in paediatric IBD using the MISS questionnaire.


From July to November 2014, patients with paediatric IBD followed in the IBD clinic of Sainte Justine hospital who had received at least 2 months of MTX along with their parents were contacted by telephone and invited to complete the MISS questionnaire. A cut-off score of >=6 points with >=1 points for anticipatory and/or associative and/or behavioural items was used to define MTX intolerance.


Sixty-four patients and 44 parents completed the MISS questionnaire. Two patients refused to participate. MTX treatment had been initiated between 2004 and 2009 for 23 patients and between 2010 and 2014 for 41. Thirty-eight patients (59%) were males and mean age (±SD) at initiation of MTX was 13.4 ± 3.7 years. Thirty-two (50%) and 27 (42%) were deemed intolerant to MTX based on the responses of the child and parents, respectively. The mean (±SD) MISS score was 6.2 ± 5.8 for children and 6.8 ± 6.9 according to parents. There was a good correlation between parents' and children's answers: r=0.77.

Seventy percent of patients had gastrointestinal symptoms after taking MTX, 52% had symptoms when thinking of MTX (associative), 52% had symptoms prior to taking MTX (anticipatory) and 50% had behavioural symptoms. Prevalence of gastrointestinal symptoms was: 38% abdominal pain, 72% nausea, and 25% vomiting. The other symptoms noted were headaches (n=4), fatigue (n=2), alopecia (n=1) and negative conditioning to ondansetron (n=1).


MTX intolerance is frequent in paediatric IBD. The MISS questionnaire was feasible and could be implemented to identify early those patients who are most likely to develop MTX intolerance, precluding the need to discontinue treatment after initiation. Further studies seeking to identify clinical and socio-demographic factors predisposing to MTX intolerance are currently being pursued.


[1] Bulatovic M et al., (2011), High Prevalence of Methotrexate Intolerance in Juvenile Idiopathic Arthritis, Arthritis & rheumatism, 2007-2013