Switching Between Infliximab Originator and Biosimilar in Paediatric Patients with Inflammatory Bowel Disease. Preliminary Observations.

BACKGROUND AND AIMS: The growing incidence of inflammatory bowel disease (IBD) in children necessitates the use of biological treatments. Recently, an infliximab biosimilar was authorized in the European Union, which may result in switching patients. We present our preliminary experiences with such switches. METHODS: The prospective study included 32 paediatric patients diagnosed with Crohn's disease (CD) and 7 children with ulcerative colitis (UC) at 3 academic hospitals, who were switched from infliximab originator to its biosimilar (Remsima). Patient characteristics, disease severity, laboratory parameters and adverse events were recorded. Means, medians and ranges were calculated. RESULTS: Mean age at diagnosis of CD and UC was 11.1 (2.7-15.3) and 12.3 years (8.5-14.8), respectively. Mean number of infliximab originator infusions before switching to the biosimilar was 9.9 (median 8, range 4-29) and 5.1 (5, 1-12) for the CD and UC group, respectively. Evaluation efficacy of last biosimilar doses of all patients revealed rates of clinical remission of 88 and 57% for CD and UC patients, respectively. Last follow-up assessment of patients who continued with biosimilar therapy showed that 16/20 (80%) CD patients and all 4 UC individuals were in remission. One infusion reaction to infliximab biosimilar was observed in a CD patient, which led to treatment discontinuation. The incidence of sporadic mild adverse events prior to and after switching did not differ significantly and was consistent with the safety profile of the infliximab molecule. CONCLUSION: Switching from infliximab originator to its biosimilar seems to be a safe option in children with CD. After the switch the biosimilar was just as effective as the originator.

The nutritional status and factors contributing to malnutrition in children with chronic pancreatitis.

BACKGROUND/OBJECTIVES: The present study was undertaken to determine the prevalence of malnutrition among children with chronic pancreatitis (CP). Furthermore, we aimed to evaluate the relationship between etiological factors of CP, its clinical characteristics, and the severity of malnutrition. METHODS: The study included 208 children with CP (113 girls and 95 boys; mean age: 10.8 years, range: 1.6-18 years), hospitalized at our center between 1988 and 2012. The severity of malnutrition was graded on the basis of Cole's ratios, and its prevalence was analyzed according to the etiological factors of pancreatitis. Moreover, the analysis of discrimination was performed to identify the factors contributing to malnutrition among the following variables: age at CP onset, duration of CP, number of CP exacerbations, the number of ERCPs performed, the grade of pancreatic damage documented on imaging, co-occurrence of diabetes, and the results of 72-h fecal fat quantification. RESULTS: We documented features of malnutrition in 52 (25%) children with CP, including 36 (17.3%) patients with moderate malnutrition, and 2 (0.96%) with severe malnutrition. There was no significant difference in the prevalence of malnutrition between groups of patients with various etiological factors of chronic pancreatitis. The age at CP onset showed the best discrimination ability of malnourished patients: the mean age at disease onset in a subgroup of malnourished children was significantly higher than in children with Cole's index >85%. CONCLUSIONS: A considerable percentage of children with CP can suffer from clinically significant malnutrition. Later age at CP onset predisposes to development of malnutrition.

Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease.

Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

Diagnosis of gastroesophageal reflux and anti-reflux procedures among Polish children with gastrostomies: a 10-year nationwide analysis.

BACKGROUND/OBJECTIVES: To analyse the approach to diagnose gastroesophageal reflux (GER) and the qualification criteria for anti-reflux (AR) procedures in Polish children fed via gastrostomy between 2000 and 2010. SUBJECTS/METHODS: An electronic questionnaire containing questions on the demographic and clinical data of patients with gastrostomies was distributed to six Polish centres of nutritional therapy. The portion pertaining to GER included data on clinical exponents, diagnostic procedures (pH-metry, pH-impedance, scintigraphy and upper gastrointestinal (GI) series) and AR. RESULTS: In total, 348 children (M199/F149; age at gastrostomy 5.78±5.49 years) were included. Data on the diagnosis of GER and the AR criteria were available for 343 and 336 subjects, respectively. Percutaneous endoscopic gastrostomy was performed in 258/348 patients (74.1%), while surgery was performed in 80/348 patients (23%). The data from 10/348 (2.9%) cases were unavailable. At least one of the tests for GER was conducted in 177/343 (51.6%) of patients: pH-metry in 74/343 (21.6%), pH-impedance in 17/343 (5.0%), scintigraphy in 60/343 (17.5%) and upper GI series in 102/343 (29.7%). GER was reported in 114/343 cases (33.2%), and fundoplication was performed in 87 children (76.3% of patients with GER). The highest congruence between a positive test result and the decision to perform fundoplication was documented in cases of scintigraphy and upper GI series (P=0.00000 and P=0.00191, respectively). A significant increase in the prevalence of simultaneous gastrostomy and AR was observed over the decade analysed (r=0.8, P=0.009). This study revealed a centre-specific attitude towards the diagnosis of GER and the assessment of qualifications for fundoplication in Polish gastrostomy-fed children. CONCLUSIONS: The unified diagnostic algorithm of GER and the universal qualification criteria for AR procedures need to be defined for gastrostomy-fed children.

Aluminum contamination of parenteral nutrition additives, amino acid solutions, and lipid emulsions.

Contamination of parenteral nutrition solutions with aluminum may result in accumulation of this element in bones and, in premature infants, may inhibit bone calcium uptake and induce cholestasis. We measured the aluminum concentration of small-volume parenterals, amino acid solutions, lipid emulsions, and special solutions containing glucose, amino acids, electrolytes, and trace elements (standard I for children with a body weight of 3-5 kg, standard II for children with a body weight of 5-10 kg). The method used was graphite furnace atomic absorption spectrometry GTA-AAS (SpectrAA-400 Plus, Varian, PtY Ltd., Mulgrave, Australia). Quality control was run with the use of control serum (Seronorm, Nycomed, Oslo, Norway). The aluminum contents of parenterally administered solutions were: pediatric trace elements, 130 micrograms/L, and pediatric trace elements, 3000 micrograms/L; phosphorus salts: K-phosphates, 9800 micrograms/L, and Na/K phosphates, 13,000 micrograms/L; 10% calcium gluconate, 4400 micrograms/L; 6.5% amino acids, 30 micrograms/L; 10% amino acids, 120 micrograms/L; 12.5% amino acids, 121 micrograms/L; 20% lipid emulsion, 30 micrograms/L; 20% lipid emulsion, 180 micrograms/L; water-soluble vitamins, 12 micrograms/L; lipid soluble vitamins, 360 micrograms/L; standard I, 55 micrograms/L; standard II, 90 micrograms/L; The aluminum intake from parenteral nutrition was 6.6-10.8 micrograms.kg-1.d-1--a dose exceeding the safety limit of 2 micrograms.kg-1.d-1. The possible association of aluminum not only with metabolic bone disease, but also with encephalopathy, dictates caution when dealing with the pediatric population on long-term parenteral nutrition. In the absence of reliable label information, it seems proper to monitor the aluminum concentration in parenteral nutrition products and to report it in professional journals.

Home parenteral nutrition in children: the Polish experience.

BACKGROUND: Home parenteral nutrition has become routine for management of intestinal failure in patients. In Poland the main obstacle to widespread use of home parenteral nutrition is the lack of interest of commercial companies in delivering feedings and ancillaries to patients. METHODS: Twenty-five home parenteral nutrition patients aged from 4 months to more than 13 years were reviewed. The mother or both parents were trained in home parenteral nutrition techniques for 4 to 6 weeks and compounded the nutrients themselves at home. RESULTS: The mean duration of home parenteral nutrition was 10,117 patient days. Hospital stays of patients receiving parenteral feedings were significantly shorter than the duration of administration of home parenteral nutrition (p < 0.001). Eleven children are continuing the home parenteral nutrition program. Eighty-three catheters were used in these patients. The rate of catheter occlusion decreased within the observation period, and in 1997 not one case of occlusion was observed. In 1997 only three catheters were removed during 7.8 patient years, and the overall incidence of catheter-related complications was 0.38 per patient year. The overall occurrence of septicemia was one case in 516 days and of catheter infection was one in 459 days. In 1997 a catheter was infected on average of once every 1419 days. There was significant improvement in the z score for weight during therapy. The average monthly cost of nutrients and ancillary items was approximately $1200 (4200 Polish zlotys [PLN]). These costs are 1.6 to 3 times lower than those recorded in other studies. CONCLUSION: Home parenteral nutrition in children with nutrients mixed by caregivers in the home setting is a safe and appropriate method of treatment that can be used in countries where home parenteral nutrition solutions are not manufactured or where commercial home parenteral nutrition is not economically feasible.

Is growth hormone a feasible adjuvant in the treatment of children after small bowel resection?

The aim of our study was to assess the metabolic consequences of short-term administration of growth hormone in children after gut resection and influence on polyamine production in red blood cells (RBC). Twelve children aged 4-60 months were studied. All children remained on parenteral nutrition and 11 also received oral feeding. Total non-protein energy intake was 429 +/- 86 kJ/kg body weight (BW)/day. Recombinant growth hormone (GH) was administered subcutaneously at a dose of 0.3 IU/kg BW/day for 10 days. Resting energy expenditure (REE; kJ/kg BW/day) was: 316.07 +/- 54.08 before and 346.04 +/- 54.40 during GH administration (P < 0.02), but daily weight gain before GH administration was significantly lower than during treatment. A significant increase of polyamine concentrations was observed in the RBC (spermidine: 30.1 +/- 15.1 and 43.8 +/- 24.9 nmol/ml packed RBC, P < 0.003; spermine: 15.6 +/- 5.1 and 19.6 +/- 10.6 nmol/ml packed RBC, P < 0.02) and in jejunal mucosa (spermidine: 172.10 +/- 142.35 nmol/g tissue and 193.92 +/- 108.15 nmol/g tissue). The authors concluded that increased polyamine concentrations in the RBC and jejunal mucosa reflect a cellular response to GH administration. The anabolic effect of GH results in higher weight gain, although increased REE may indicate increased energy requirements during GH treatment.

Energy metabolism in portal hypertension in children.

This study was designed to assess resting energy expenditure (REE) and nutritional status in children with hepatic and prehepatic portal hypertension in comparison with healthy controls. Twenty-five patients with portal hypertension (PHT) and a history of variceal bleeding were compared with 14 healthy volunteers selected after matching for age and sex. PHT patients were allocated to one of two groups: 11 children with liver cirrhosis and/or chronic hepatitis, aged 14.0 +/- 3.3 y (means +/- SD) or 14 children with extrahepatic portal vein obstruction, aged 12.3 +/- 2.8 y. The control group consisted of 14 healthy children, aged 14.0 +/- 1.8 y. REE (indirect calorimetry) assessed after an overnight fast was significantly higher in PHT patients than in controls when related to body mass (143.7 +/- 29.5 and 116.1 +/- 5.9 kJ/kg, respectively; p < 0.004), lean body mass (168.0 +/- 28.9 and 146.4 +/- 14.1 kJ/kg, respectively; p < 0.02), and body surface area (7480 +/- 736 and 6590 +/- 567 kJ/1.73 m2, respectively; p < 0.001). The ratios of measured REE to basal energy expenditure calculated from standard equations (Schofield equations) indicated higher REE in PHT patients (102.24 +/- 6.90% and 93.54 +/- 4.47%, respectively; p < 0.001). Fat was the predominant source of energy in both PHT patients and controls; the percentage of nonprotein energy derived from carbohydrate oxidation was equaled: 36.04 +/- 18.84% and 37.15 +/- 15.71%, respectively. Analysis of percentage of undernutrition in PHT patients and controls revealed significant differences (44% and 21%, respectively; p < 0.001). Children with PHT are susceptible to malnutrition and have elevated REE compared with healthy controls. Fat is the principal basal state oxidative substrate for patients with PHT and healthy children.

[Thermogenesis during parenteral nutrition and after oral meal]. / Termogeneza podczas zywienia pozajelitowego i po posilku doustnym.

The aim of the study was to assess thermogenesis during parenteral feeding (group A) and after an oral test meal of a polymeric diet (group B). Carbohydrates, fat and protein ratios in the oral meal and parenteral mixture were: 51:34:15 and 76:11:13, resp. In both situations 20% of resting energy expenditure (REE) was administered-as a bolus oral meal or during 120 min. of intravenous infusion. Mean results of respiratory gas exchange of 15 min. periods were used for calculations. Basal respiratory quotient (RQ) in group A and B was 0.841 and 0.806 resp (difference not significant; NS); peak RQ was 0.910 and 0.924 resp. (NS). Peak RQ in group B was significantly higher than basal (p < 0.006). REE in group A and B was 1,416 +/- 0,231 kj/kg/15 min. and 1,322 +/- 0,226 kj/kg/15 min. resp. (NS). Peak thermic effect (expressed as the rise of REE in percent of the energy content of the nutrients) was: 4.778% and 5.135% resp. (NS). Postprandial thermogenesis is not dependent on the route of administration of nutrients (parenteral or oral). The proportion of substrate utilisation depends on the content of the meal or parenteral mixture.

[Autoimmune enteropathy--difficulties in diagnosis and treatment]. / Biegunka autoimmunologiczna--trudnosci w diagnostyce i leczeniu.

We describe a 42-month-old child with protracted diarrhoea that began at 6 months of age. Severe secretory diarrhoea persisted despite therapy with exclusion diets, total parenteral nutrition, chemotherapeutics, antisecretory drugs. The diagnosis of autoimmune enteropathy with total villous atrophy and anti-enterocyte antibodies was established at 16 months of age. Prednisone therapy induced a clinical remission. After dose reduction, clinical relapse occurred, complicated with HCV infection with elevated serum alanine aminotransferase activity. Increasing the prednisone dose did not result in clinical improvement. Treatment with cyclosporine induced clinical remission. After 10 months cyclosporine therapy is still continued and the boy is doing well.