Switching From Originator to Biosimilar Infliximab in Paediatric Inflammatory Bowel Disease Is Feasible and Uneventful.

The safety, clinical efficacy, and cost-effectiveness of biosimilar infliximab in adult inflammatory bowel disease (IBD) have now been extensively shown. Limited data have been collected in the paediatric setting. We report nationwide, prospective, clinical safety and effectiveness data for patients from all 3 Scottish paediatric inflammatory bowel disease networks switching from originator to biosimilar infliximab. Prospective clinical data were collected for 33 patients. Information was collected from electronic patient records, laboratory reports, and patient case notes. There were no clinically significant changes to disease activity, biomarkers, antidrug antibodies, or trough drug levels (P > 0.1) within a 12-month follow-up period; in addition, there were no significant adverse events reported. No infusion reactions were seen in the 264 infusions delivered. Switching from originator infliximab to the biosimilar (CT-P13) appears to be associated with neither an increase in infusion reactions nor significant loss of effectiveness in the short term.

Efficacy of oral methotrexate in paediatric Crohn's disease: a multicentre propensity score study.

BACKGROUND: Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn's disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD. METHODS: 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and 'doubly robust' weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups. RESULTS: 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test). CONCLUSIONS: In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

Systematic review: the role of breastfeeding in the development of pediatric inflammatory bowel disease.

OBJECTIVES: To assess the current evidence for the role of breastfeeding in the development of early onset inflammatory bowel disease (IBD) with a systematic review. STUDY DESIGN: An electronic database search was performed (January 1966-January 2008) with keywords related to IBD and breastfeeding, looking specifically for studies that reported outcome in early-onset disease (<16 years of age) and "any exposure" to breast milk as the variables. Meta-analysis of studies included for review was then performed by using a random effects model, and results were expressed as odds ratios (OR) with 95% CIs. RESULTS: A total of 79 articles were identified, 20 of which were found describing breastfeeding in relation to the development of IBD; 8 of these articles included separate early-onset groups. One study did not describe "any exposure" to breast milk for the early onset group, so 7 studies were included in the meta-analysis. Breast milk exposure had a significant protective effect (OR, 0.69; 95% CI, 0.51-0.94; P = .02) in developing early-onset IBD. A non-significant difference was demonstrated for ulcerative colitis and Crohn's disease individually (OR, 0.72; 95% CI, 0.51-1.02; P = .06; OR, 0.64; 95% CI, 0.38-1.07; P = .09, respectively). CONCLUSIONS: The current evidence demonstrates a possible protective effect for breast milk in the development of early onset IBD. However, the quality of existing data is generally poor. These findings need to be investigated in well-designed prospective studies.

Mycoplasma pneumoniae associated with hemolytic anemia, cold agglutinins, and recurrent arterial thrombosis.

A 40-year-old white male developed Mycoplasma pneumoniae pneumonia (IgM titer 1:256) as well as autoimmune hemolytic anemia due to cold agglutinins (titer of 1:512). Four days after admission to the hospital, he developed an acute superior mesenteric artery (SMA) thrombosis. Four feet of ischemic small bowel were resected. A follow-up angiogram again showed SMA thrombosis and a left popliteal artery thrombosis. The patient was returned to the operating room and underwent thrombectomy of the affected arteries. The following day, he again developed a left popliteal artery thrombosis requiring thrombectomy. Plasmapheresis, Coumadin and prednisone were implemented. No further thrombotic events occurred. Hypercoagulability workup was negative. Pathology samples revealed vasculitis. Based on a negative hypercoagulability workup, nonrecurrence of thrombotic events after treatment, and in the absence of any structural abnormalities of the affected arteries, an autoimmune phenomenon with damage to the endothelium was thought to have played a role in the mechanism of thrombosis.

Quantification of optison bubble size and lifetime during sonication dominant role of secondary cavitation bubbles causing acoustic bioeffects.

Acoustic cavitation has been shown to deliver molecules into viable cells, which is of interest for drug and gene delivery applications. To address mechanisms of these acoustic bioeffects, this work measured the lifetime of albumin-stabilized cavitation bubbles (Optison) and correlated it with desirable (intracellular uptake of molecules) and undesirable (loss of cell viability) bioeffects. Optison was exposed to 500 kHz ultrasound (acoustic pressures of 0.6-3.0 MPa and energy exposures of 0.2-200 J/cm2) either with or without the presence of DU145 prostate cancer cells (10(6) cells/ml) bathed in calcein, a cell-impermeant tracer molecule. Bubble lifetime was determined using a Coulter counter and flow cytometer, while bioeffects were evaluated by flow cytometry. The lifetime of Optison cavitation nuclei was found to decrease and bioeffects (molecular uptake and loss of cell viability) were found to increase with increasing acoustic energy exposure. These bioeffects correlated well with the disappearance of bubbles, suggesting that contrast agent destruction either directly or indirectly affected cells, probably involving unstabilized cavitation nuclei created upon the destruction of Optison. Because Optison solutions presonicated to destroy all detectable bubbles also caused significant bioeffects, the indirect mechanism involving secondary cavitation bubbles is more likely.