Ewa Toporowska-Kowalska

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 Crohns 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.

Insulin sensitivity in Type 1 diabetic children and adolescents.

Aim  To estimate insulin sensitivity in Type 1 diabetic children and adolescents, and assess the relationship between insulin sensitivity and clinical markers of adiposity and parameters of the metabolic syndrome.

Monotherapy with infliximab versus combination therapy in the maintenance of clinical remission in children with moderate to severe Crohn disease.

Objectives: The aim of the present study was to compare the efficacy and safety of 2 protocols of maintenance therapy with infliximab (IFX) and an immunomodulatory agent in pediatric patients with Crohn disease (CD): withdrawal of immunomodulators versus continuation of immunosuppressants. Methods: The present multicenter randomized open-label trial included 99 patients with CD (ages 14.5 ± 2.6 years) who were administered IFX (5 mg/kg body weight) along with an immunomodulatory agent (azathioprine 1.5–3 mg/kg body weight per day, methotrexate 10–25 mg/week). After 10 weeks of the induction therapy, 84 responders were centrally randomized into 1 of the following groups: group I (n = 45) in which IFX and an immunomodulatory agent were continued up to week 54 and group II (n = 39) in which the immunomodulatory agent was discontinued after 26 weeks. Results: The induction therapy was reflected by a significant decrease in Pediatric Crohns Disease Activity Index (PCDAI) and Simplified Endoscopic Activity Score for Crohns Disease (SES-CD) values. After the maintenance phase, the analyzed groups did not differ significantly in terms of the clinical response loss rates and final PCDAI and SES-CD scores. Furthermore, no significant intragroup differences were documented between mean PCDAI scores determined at the end of induction and maintenance phases. Intensification/modification of the treatment was required in 13 of 45 (29%) and 11 of 39 (28%) patients of groups I and II, respectively. A total of 9 serious adverse events were documented; none of the patients died during the trial. Conclusions: Twenty-six weeks likely represent the safe duration of combined IFX/immunomodulatory therapy in our sample of pediatric patients with CD.

Influence of percutaneous endoscopic gastrostomy on gastro-oesophageal reflux evaluated by multiple intraluminal impedance in children with neurological impairment

Aim  The aim of the study was to estimate the influence of percutaneous endoscopic gastrostomy (PEG) placement on gastro‐oesophageal reflux (GOR) by using multiple intraluminal impedance (MII/pH) measurements in children with neurological impairments.

Induction Therapy With Biosimilar Infliximab in Children With Crohn Disease

Introduction: In most European countries, an infliximab biosimilar (CT-P13) is currently in common use. In vitro and in vivo studies have proved a high similarity between CT-P13 and the reference infliximab. CT-P13 was licensed for use in patients with Crohn disease (CD) based on the extrapolation of data from preclinical studies and clinical trials in rheumatology indications. The aim of this study was to assess the similarity between CT-P13 and the originator infliximab in induction therapy in CD paediatric patients. Methods: Thirty-six CD paediatric patients from 3 Polish academic centres who started biological therapy with CT-P13 were enrolled in this prospective, observational study. Patients received 3 induction doses (5 mg/kg) of CT-P13 at weeks 0, 2, 6. Assessment was performed before the first infusion and at week 14. Results: Overall 34/36 (94.4%) patients completed induction therapy with CT-P13. A clinical response or remission after 3 initial doses was achieved in 31/36 (86%) and 24/36 (67%) of patients, respectively. Clinically and statistically significant decreases in Paediatric Crohns Disease Activity Index, C-reactive protein, and erythrocyte sedimentation rate were observed in the responders group. An allergic reaction during infusion, which led to treatment discontinuation, was observed in one case. Conclusions: Induction therapy with CT-P13 in children with CD is effective. The profile appears similar to that reported for the reference infliximab. No unexpected adverse events occurred.

Prevalence of EGG derangement in newly diagnosed type 1 diabetes in childhood.

Objective: To evaluate gastric myoelectrical activity in children with newly diagnosed type 1 diabetes melliltus (T1DM) in relation to blood glucose control and visceral neuropathy. Methods: Percutaneous electrogastrograpy (EGG) was performed on 42 children (20 F; mean age 12.9 ± 3.1 years) with T1DM of <1 years duration and on 35 healthy controls (18 F; mean age 13.4 ± 3.6 years). After overnight fasting, a 30-minute EGG recording was followed by test meal consumption and then a 60-minute postprandial EGG aquisition. Fasting and postprandial periods were analyzed for gastric dysrhythmias, dominant frequency (DF) and additional parameters. In T1DM patients, HbA1c and blood glucose levels were measured and tests for visceral neuropathy were performed. Results: In 41 T1DM patients (98%), cardiovascular neuropathy tests were negative. In 12 of those patients (29%) and in 32 healthy controls (91%), electrogastrograms were normal. The percentages of fasting and postprandial gastric dysrhythmias were significantly higher in T1DM patients compared to controls (P < 0,05). In T1DM children after feeding, some normalization of gastric myoelectrical rhythm was observed: normogastria increased nearly 2-fold to 72.6 ± 22.9% and bradygastria decreased to 20.8 ± 20.4% from 52.3 ± 32.4% (P < 0.05). The percentages of fasting bradygastria and normogastria were correlated with glycemia level (r = −0.55 and r = 0.51, respectively; P < 0.05), as was postprandial DF (r = 0.41; P < 0.05). There was no correlation between HbA1c levels and EGG parameters. Conclusions: Derangement of the gastric myoelectrical activity is present in 71% of children with early stage T1DM. Glucose levels influence gastric myoelectrical activity, whereas long-term glucose control (HbA1c level) does not correlate with EGG parameters.

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.

Electrogastrography in children and adolescents with type 1 diabetes: Weak correlation with metabolic control parameters

Aim: To evaluate gastric myoelectrical activity with respect to duration and metabolic control of type 1 diabetes mellitus (T1DM). Methods: 172 children and adolescents with T1DM (mean 14.4±3.7 y), divided into subgroups depending on diabetes duration (<5 and > 5 y), and 35 healthy controls (mean 13.93±3.59 y) were examined. All subjects underwent electrogastrography (EGG) performed after overnight fasting. In subjects with T1DM, haemoglobin A1c (HbA1c) and blood glucose levels during EGG records were measured. Results: 15.69% of T1DM patients and 91.42% of the controls fulfilled normal EGG criteria (p < 0.001). T1DM subjects had a lower percentage of fasting normogastria (34.56±27.35% vs 69.84±18.16%, p = 0.0001) and higher bradygastria (51.97±30.24% vs 19.11±15.01%, p = 0.0001) compared to controls. In diabetic patients, an increase in postprandial normogastria (60.37±23.96% vs 76.68±12.38, p < 0.05) and a decrease in bradygastria percentage (25.67±21.01% vs 9.58±7.13%, p < 0.05) was observed. In children with disease < 5 y, diabetes duration correlated with power ratio (r= ‐ 0.27, p = 0.01), postprandial normogastria (r= ‐ 0.24, p = 0.03) and tachygastria (r= 0.25, p = 0.02). Weak correlations between EGG parameters and glucose (preprandial dominant frequency r= ‐ 0.19, p < 0.05; postprandial normogastria r= 0.23, p < 0.01) and HbA1c levels (preprandial bradygastria r= 0.19, postprandial dominant power r= 0.23; p < 0.05) were observed.

Complications of PEG are not related to age – The result of 10-year multicenter survey

PURPOSE The aim of this study was to analyze whether the insertion of Percutaneous Endoscopic Gastrostomy (PEG) during infancy is related to higher morbidity. Moreover, we analyzed the structure of indications to PEG placement in various age groups of pediatric patients. MATERIAL/METHODS The study involved medical data of children after PEG insertion from six Polish endoscopic centers: infants (<12 months of age), toddlers (12-36 months), and preadolescents (>36 months). RESULTS The overall prevalence of early complications associated with PEG insertion was 5.14%; while they were noted in infants and preadolescents, none were recorded in toddlers. The analyzed age groups did not differ significantly in terms of the prevalence of late complications. Cerebral palsy (34.86%) and other chronic neurological conditions (34.29%) were the most frequent indications to PEG insertion in the whole group. Patients with congenital heart defects and multiple defect syndrome were inserted PEG at the youngest age; in contrast, the age at insertion was the highest in cystic fibrosis patients. CONCLUSIONS The early qualification to nutritional intervention via endoscopically formed gastrostomy can have important clinical implications with regards to improved therapeutic outcomes and reduced morbidity rates.

Immunogenicity of Pertussis Booster Vaccination in Children and Adolescents with Inflammatory Bowel Disease: A Controlled Study

Background: There are limited data on antibody response to vaccination in patients with inflammatory bowel disease (IBD). In this study, we aimed to assess the immunogenicity of a booster dose of pertussis vaccine in pediatric patients with IBD and to compare their response with healthy controls. Methods: We performed a multicenter, prospective, and controlled trial. Eligible for inclusion were children and adolescents (11–18 year olds), with no history of pertussis booster immunization after the age of 6 years or history of pertussis. Study population was divided into 4 groups: patients with IBD receiving no immunosuppressive therapy (group 1), those on thiopurines only (group 2), those on thiopurines and TNF-&agr; agents (group 3), and healthy controls (group 4). Patients and controls received 1 dose of pertussis vaccine intramuscularly and were asked to record adverse effects for 3 days after vaccination. The primary outcome measure was adequate vaccine response, defined as the concentration of anti-Bordetella pertussis antibodies >11 &mgr;g/mL, measured between 4 and 8 weeks after the vaccination. Results: In total, 138 subjects (111 patients and 27 controls) were enrolled in the study. Rates of adequate vaccine response did not differ among the 4 study groups (P = 0.11). Moreover, those patients with IBD who were on immunosuppressive therapy did not differ from those who were not (90.6% versus 88.2%, P = 0.37). No serious adverse effects in relation to the administration of vaccine were noted. Conclusions: Booster dose of pertussis vaccine was immunogenic and safe in pediatric patients with IBD.