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Hepatotoxicity caused by methotrexate therapy in children with inflammatory bowel disease: a systematic review and
Pamela L Valentino1, Peter C Church, Prakeshkumar S Shah
11Division of Gastroenterology, Hepatology, and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 2Neonatal Intensive Care Unit, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Toronto, ON, Canada; and 4Division of Rheumatology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Background:
Methotrexate (MTX) is an immunomodulator used in pediatric inflammatory bowel disease (IBD) maintenance regimens. However, MTX use is associated with liver toxicity. We aimed to systematically review and meta-analyze the incidence of hepatotoxicity with MTX use among children with IBD.
Methods:
We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases from 1946 to April 2013 for cohort studies and collected information about the study design, IBD treatment results, and hepatotoxicity. Pooled proportions of toxicity with 95% confidence interval (CI) were estimated using a random-effects model.
Results:
Twelve high-quality studies were included in this review. Fifty-seven of 457 patients treated with MTX developed varied degrees of abnormal liver biochemistry. The pooled proportion of patients with abnormal liver biochemistry was 10.2% (95% CI 5.4%-18.5%) across all studies included in the meta-analysis. Due to hepatotoxicity, dose reductions were required in 6.4% (95% CI 4.3%-9.5%), whereas 4.5% (95% CI 2.8%-7.2%) of patients required discontinuation.
Conclusions:
Hepatotoxicity after the use of MTX among IBD patients was a relatively common event. Monitoring for hepatotoxicity is strongly recommended, as discontinuation of MTX may be necessary in a significant proportion of children.
Insights
Methotrexate (MTX) can cause liver issues in children with inflammatory bowel disease (IBD). About 10.2% experienced abnormal liver tests, with some needing dose changes or stopping MTX treatment.
Area of Science:
- Pediatric Gastroenterology
- Clinical Pharmacology
- Immunomodulatory Therapies
Background:
- Methotrexate (MTX) is a key immunomodulator for pediatric inflammatory bowel disease (IBD) maintenance.
- MTX use is linked to potential liver toxicity, a significant concern in this population.
- Systematic review and meta-analysis are needed to quantify MTX-associated hepatotoxicity in pediatric IBD.
Purpose of the Study:
- To systematically review and meta-analyze the incidence of hepatotoxicity in children with IBD treated with MTX.
- To provide a pooled estimate of MTX-induced liver injury in this specific patient group.
- To inform clinical practice regarding the safety profile of MTX in pediatric IBD.
Main Methods:
- Comprehensive literature search of major biomedical databases (MEDLINE, EMBASE, Web of Science, Cochrane).
- Inclusion of high-quality cohort studies evaluating MTX use and hepatotoxicity in pediatric IBD patients.
- Random-effects model employed to estimate pooled proportions and 95% confidence intervals (CI) for hepatotoxicity outcomes.
Main Results:
- Twelve studies involving 457 patients treated with MTX were analyzed.
- The pooled incidence of abnormal liver biochemistry was 10.2% (95% CI 5.4%-18.5%).
- Hepatotoxicity led to dose reductions in 6.4% (95% CI 4.3%-9.5%) and discontinuation in 4.5% (95% CI 2.8%-7.2%) of patients.
Conclusions:
- Hepatotoxicity is a relatively common adverse event associated with MTX use in pediatric IBD.
- Close monitoring for liver function abnormalities is crucial in children receiving MTX.
- A significant proportion of pediatric IBD patients may require MTX dose adjustments or discontinuation due to hepatotoxicity.
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