Prevalence and Risk Factors for Symptoms of Methotrexate Intolerance in Pediatric Inflammatory Bowel Disease

Dupont-Lucas, Claire; Grandjean-Blanchet, Charlotte; Leduc, Bertrand; Tripcovici, Martina; Larocque, Christine; Jantchou, P; Amre, Devendra; Deslandres, Colette

doi:10.1097/mib.0000000000001014

Cited by 13 publications

(14 citation statements)

References 19 publications

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“…It has even been proposed that antiemetic medicine should be introduced very early in order to avoid the development of a conditioned response–i.e. anticipatory nausea [23,24]. Supported by Dupont-Lucas et al [24] who found that children with inflammatory bowel disease receiving antiemetic medicine secondarily, compared to prophylactic, were more likely to be MTX intolerant.…”

Section: Discussionmentioning

confidence: 99%

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Increased methotrexate intolerance in juvenile idiopathic arthritis compared to acute lymphoblastic leukaemia in children

et al. 2019

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Objectives To 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). Methods Cross-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. Results We 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. Conclusion In 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.

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Section: Discussionmentioning

confidence: 99%

“…anticipatory nausea [23,24]. Supported by Dupont-Lucas et al [24] who found that children with inflammatory bowel disease receiving antiemetic medicine secondarily, compared to prophylactic, were more likely to be MTX intolerant. Once anticipatory and associative symptoms are present a psychological intervention–e.g.…”

Section: Discussionmentioning

confidence: 99%

Increased methotrexate intolerance in juvenile idiopathic arthritis compared to acute lymphoblastic leukaemia in children

et al. 2019

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“…106 In a retrospective study, 31% of 102 pediatric patients with IBD experienced methotrexate intolerance (gastrointestinal or behavioral symptoms). 110 Strategies to reduce these effects in children have been reported. 111 Other adverse events included elevated liver function tests, headache, and hematologic toxicity.…”

Section: Recommendation Statementsmentioning

confidence: 99%

Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn’s Disease

Mack

Benchimol

Critch

et al. 2018

Journal of the Canadian Association of Gastroenterology

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Background & AimsWe aim to provide guidance for medical treatment of luminal Crohn’s disease in children.MethodsWe performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn’s disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them.ResultsThe consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation.ConclusionsEvidence-based medical treatment of Crohn’s disease in children is recommended, with thorough ongoing assessments to define treatment success.

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“…Recently two large studies on anti-emetics for MTX-intolerance in pediatric patients have been published, providing some evidence against the conclusion by Falvey et al [ 4 , 5 ]. Scheuern et al described the results of a prospective, observational study in 196 JIA patients.…”

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confidence: 99%

“…Dupont-Lucas et al performed an observational study in 102 pediatric IBD patients. They concluded: “Prophylactic prescription of anti-emetics (…) did not prevent symptoms of MTX intolerance” [ 5 ]. Both studies were not randomized, so firm conclusions cannot be drawn from these studies either.…”

mentioning

confidence: 99%

Contradictory and weak evidence on the effectiveness of anti-emetics for MTX-intolerance in JIA-patients

2018

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Prevalence and Risk Factors for Symptoms of Methotrexate Intolerance in Pediatric Inflammatory Bowel Disease

Abstract: Symptoms of MTX intolerance are frequent in pediatric IBD. The Methotrexate Intolerance Severity Score questionnaire could help better recognition of these symptoms. Identification of risk factors could have important implications for the success of treatment.

Cited by 13 publications

References 19 publications

Increased methotrexate intolerance in juvenile idiopathic arthritis compared to acute lymphoblastic leukaemia in children

Increased methotrexate intolerance in juvenile idiopathic arthritis compared to acute lymphoblastic leukaemia in children

Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn’s Disease

Contradictory and weak evidence on the effectiveness of anti-emetics for MTX-intolerance in JIA-patients

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