Safety and Efficacy of Split-Dose Thiopurine vs Low-Dose Thiopurine-Allopurinol Cotherapy in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been suggested as rescue therapeutic options for children with inflammatory bowel disease (IBD) and impaired thiopurine metabolism. We compared the efficacy and safety of these regimens in patients who previously failed conventional thiopurine treatment. METHODS: Children with IBD treated with split-dose thiopurine or low-dose thiopurine-allopurinol cotherapy were retrospectively identified. Medical records were reviewed for demographics, treatment regimen, reason for thiopurine failure, side effects, and discontinuation of treatment. Laboratory findings were evaluated at different time points. RESULTS: After prior therapeutic failure, 42 patients were on split-dose regimen (group A) and 20 patients were on thiopurine-allopurinol cotherapy (group B). Twelve patients crossed from group A to group B because of treatment failure, 1 patient was lost at follow-up, and 1 patient discontinued the treatment. The final cotherapy group comprised 29 children (group C), while the split-dose group (group D) included 31 children. Intention-to-treat analysis showed significant differences between split-dose regimen and thiopurine-allopurinol cotherapy for 6-thioguanine nucleotide (6-TGN)/6-methyl mercaptopurine (6-MeMP) ratio ( P < 0.001), 6-TGN ( P < 0.05), and 6-MeMP ( P < 0.001) at 1-3 months. As per protocol analysis, there was a significant difference between group C and group D at 6 months for 6-MeMP ( P < 0.05) and 6-TGN/6-MeMP ratio ( P < 0.05) and at 12 months for 6-MeMP ( P < 0.05) and 6-TGN/6-MeMP ratio ( P < 0.001). Side effects were more frequent in allopurinol-thiopurine cotherapy ( P < 0.05). DISCUSSION: In children with IBD and impaired thiopurine metabolism, split-dose thiopurine and low-dose thiopurine-allopurinol cotherapy are both effective therapeutic strategies. The latter shows higher efficacy but a higher side effect rate, suggesting the use of split-dose regimen as the first-line approach.

Ferric carboxymaltose treatment for iron deficiency anemia in children with inflammatory bowel disease: Efficacy and risk of hypophosphatemia.

BACKGROUND: Although intravenous ferric carboxymaltose (FCM) is effective in treating iron deficiency anemia (IDA) in paediatric inflammatory bowel disease (pIBD), no data are available on its post-infusion related risks. AIMS: We assessed the efficacy of FCM and the rate of post-infusion hypophosphatemia in a large cohort of children with IBD and IDA. METHODS: All children with IBD with IDA treated with FCM over 5-year period were reviewed. Disease activity, biohumoral assessment and treatments were evaluated at baseline, 4-6 and 12 weeks after each infusion. RESULTS: 128 patients [median age at first infusion: 13 years] were identified, 81 (63.3%) were <14 years, 10 (7.8%) <6 years. Eighty-three children (64.8%) received one infusion, whilst 45 (35.2%) repeated infusions. A significant increase in Hb (p<0.001), iron (p<0.001) and ferritin (p<0.001) was observed 4-6 and 12 weeks post-infusion. Hb gain was unrelated to disease severity. Low baseline iron was the main predicting factor for repeated infusions (p<0.05). Three patients reported infusion reactions, none <6 years. Twenty-five children had low post-infusion serum phosphate (11 were <14 years, 3 <6 years). Two children developed severe hypophosphatemia. CONCLUSIONS: FCM administration is effective for IDA management in pIBD, including children <6 years. Due to the high prevalence of post-infusion hypophosphatemia, serum phosphate monitoring should be mandatory.

Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years.

OBJECTIVES: Inflammatory bowel disease [IBD] presenting in early childhood is extremely rare. More recently, progress has been made to identify children with monogenic forms of IBD predominantly presenting very early in life. In this study, we describe the heterogeneous phenotypes and genotypes of patients with IBD presenting before the age of 2 years and establish phenotypic features associated with underlying monogenicity. METHODS: Phenotype data of 62 children with disease onset before the age of 2 years presenting over the past 20 years were reviewed. Children without previously established genetic diagnosis were prospectively recruited for next-generation sequencing. RESULTS: In all, 62 patients [55% male] were identified. The median disease onset was 3 months of age (interquartile range [IQR]: 1 to 11). Conventional IBD classification only applied to 15 patients with Crohn's disease [CD]-like [24%] and three with ulcerative colitis [UC]-like [5%] phenotype; 44 patients [71%] were diagnosed with otherwise unclassifiable IBD. Patients frequently required parenteral nutrition [40%], extensive immunosuppression [31%], haematopoietic stem-cell transplantation [29%], and abdominal surgery [19%]. In 31% of patients, underlying monogenic diseases were established [EPCAM, IL10, IL10RA, IL10RB, FOXP3, LRBA, SKIV2L, TTC37, TTC7A]. Phenotypic features significantly more prevalent in monogenic IBD were: consanguinity, disease onset before the 6th month of life, stunting, extensive intestinal disease and histological evidence of epithelial abnormalities. CONCLUSIONS: IBD in children with disease onset before the age of 2 years is frequently unclassifiable into Crohn's disease and ulcerative colitis, particularly treatment resistant, and can be indistinguishable from monogenic diseases with IBD-like phenotype.

Eosinophilic gastrointestinal disease and inflammatory bowel disease in children: is it a disease continuum?

Eosinophilic gastrointestinal disease (EGID) and inflammatory bowel disease (IBD) are two distinct disorders that share some clinical manifestations but have different diagnostic criteria. In this article, we reviewed the clinical data of three children with EGID who later developed IBD. This study is a retrospective case note review that was conducted between 2007 and 2012. EGID seems to precede IBD in some subsets of children in whom the diagnosis of IBD may take a few years to fully develop.