Agnieszka Gawrońska

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.

Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory bowel disease.

Background: There are only a few studies on immune response to routine vaccinations in children with inflammatory bowel disease (IBD), despite a strong need for this kind of study. The aim of the study was to evaluate the immunogenicity of an inactivated hepatitis A vaccine (HAV) in IBD pediatric patients compared with healthy controls. Methods: This was an open, prospective, and controlled study on anti‐HAV‐negative children and adolescents age 2‐18 years with IBD. HAV using 720 enzyme‐linked immunosorbent assay (ELISA) units were administered at 0 months and at 6‐12 months. Seroconversion and geometric mean titers were measured after each vaccine dose. The evidence of local and systemic adverse effects for 3 days after the first and second dose of vaccine was registered. Results: A total of 134 subjects (66 patients and 68 controls) completed the whole study course consisting of two doses of vaccine and six serum samples. There was no significant difference in the rate of seroconversion between IBD patients and controls when measured after the second dose of vaccine (97% versus 100%, P = 0.2407), but the rate was significantly lower in the IBD group when measured after the first dose (39% versus 64%, P = 0.00001). The mean geometric titers were statistically significantly lower in the IBD group than in the control group at all of the measured timepoints. There were no serious adverse events related to HAV during the study. Conclusions: HAV is both immunogenic and safe in pediatric patients with IBD. (Inflamm Bowel Dis 2010;)

Lack of effect of Lactobacillus GG in breast-fed infants with rectal bleeding : A pilot double-blind randomized controlled trial

Objectives: For breast-fed infants with rectal bleeding, maternal restriction of dietary protein such as cows milk proteins is often recommended; however, poor response to dietary protein restriction is of concern. This pilot study was designed to assess the effectiveness of Lactobacillus GG (LGG) in breast-fed infants with rectal bleeding. Patients and Methods: Breast-fed infants <6 months of age with rectal bleeding (defined as the presence of visible specks or streaks of blood mixed with mucus in the stool in otherwise healthy infants) were enrolled in a double-blind randomized controlled trial in which they received LGG 3 × 109 colony-forming units (n = 14) or placebo (n = 15) twice daily for 4 weeks as an adjunct to cows milk restriction in the mothers diet. Analyses were based on allocated treatment and included data from 26 infants. Results: Mean duration of rectal bleeding was similar in the LGG and control groups (17.3 ± 10.6 vs 15.4 ± 11 days; mean difference −1.9 (95% confidence interval [CI] −4 to 7). No difference was found in the number of infants with clinical resolution of rectal bleeding within 72 hours and no relapse afterward (2/11 vs 3/15, relative risk [RR] 0.9, 95% CI 0.2–3.9) and the number of infants with clinical resolution of rectal bleeding within 72 hours followed by relapse of symptoms (5/11 vs 5/15, RR 1.4, 95% CI 0.5–3.5). Breast-feeding cessation was not needed in any infant. Conclusions: These results do not support the use of LGG as an adjunct to maternal cows milk restriction in breast-fed infants with rectal bleeding.

Enterotoxigenic Clostridium perfringens infection and pediatric patients with inflammatory bowel disease.

BACKGROUND AND AIMS Clostridium difficile is the major cause of antibiotic-associated diarrhea and is the most well known bacterial pathogen associated with inflammatory bowel disease (IBD). Enterotoxigenic Clostridium perfringens has also been detected in up to 15% of antibiotic-associated diarrhea cases, and it has not been found in healthy people. The aim of this study was to investigate the prevalence of C. perfringens infection in pediatric patients with IBD. METHODS This was a prospective, controlled study evaluating pediatric IBD patients in the Department of Pediatric Gastroenterology and Nutrition in Warsaw, Poland. All of the patients were diagnosed according to the Porto criteria. There were two control groups: (1) non-IBD patients that were suspected for bacterial diarrhea and (2) healthy children. Stool samples were collected on the day of admission. C. perfringens infection diagnosis was based on a positive stool enzyme immunoassay (C. perfringens enterotoxin test kit TechLab). RESULTS 91 fecal specimens from patients with IBD were collected. The average patient age was 11.7 years in IBD group, 7.4 years in non-IBD patients with diarrhea, and 7.4 years in healthy children. The prevalence of C. perfringens infection was 9% (8/91; CI 95% 4.6-16.4). There were more Crohns patients (6/8) in the C. perfringens positive group. There was no C. perfringens infection in the two control groups. CONCLUSION Our pilot data add evidence to the hypothesis that Clostridia other than C. difficile may play a significant role in the clinical course of IBD. However, further studies are needed to confirm this.

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.

Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine in Pediatric Patients with Inflammatory Bowel Disease.

Background:There are only a few studies on immune response to pneumococcal vaccines in patients with inflammatory bowel disease (IBD); all of them assessed polysaccharide vaccines only. The aim of the study was to evaluate the immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) in IBD pediatric patients compared with healthy controls. Methods:This was a multicenter, prospective, and controlled study on children and adolescents aged 5 to 18 years with IBD with no history of pneumococcal immunization. The subjects for the study belonged to one of the following groups: patients with IBD on no immunosuppressive therapy (group A), those on tumor necrosis factor agents or immunomodulators (group B), and healthy controls (group C). The study population received 1 intramuscular injection of PCV13. The primary outcome measure was adequate vaccine response defined as postvaccination titer ≥0.35 &mgr;g/mL to all 13 serotypes. Geometric mean titers and geometric mean titer rises were measured for all serotypes. The evidence of local and systemic adverse effects for 5 days after the vaccine was registered. Results:A total of 178 subjects (122 patients and 56 controls) completed the study course. There was no significant difference in the rate of adequate vaccine response between patients with IBD and controls measured 4 to 8 weeks after vaccination (90.4% versus 96.5%, P = 0.5281). Children in group A had higher geometric mean titer rises than children in group B (P = 0.0369). There were no serious adverse events related to PCV13 during the study. Conclusions:PCV13 is both immunogenic and safe in pediatric patients with IBD.

Overweight and obesity in children with newly diagnosed inflammatory bowel disease

PURPOSE Determination of overweight and obesity prevalence in children with inflammatory bowel disease (IBD) at the time of diagnosis. MATERIAL AND METHODS This was a multicenter retrospective study. The study group consisted of children with new cases of IBD diagnosed in 2005-2013 according to the Porto criteria. Hospital admission records were reviewed for demographic and clinical characteristics. BMI-for-age and gender percentile charts were used to define overweight as ≥85th BMI percentile and obesity as ≥95th BMI percentile. RESULTS 675 patients were evaluated: 368 with Crohns disease (CD) and 307 with ulcerative colitis (UC). Of these, 54.8% were boys and 45.2% were girls. There were no statistically significant differences in age, weight, height and disease activity between the CD and UC patients. The UC patients had higher BMI values than the CD patients. The prevalence of overweight and obesity was higher in the UC than the CD patients (4.89% CI95 2.76-7.93 vs. 2.45% CI95 1.12-4.59 and 8.47% CI95 5.61-12.16 vs. 1.9% CI95 0.77-3.88, respectively); the differences were statistically significant (-2.44% CI95 -5.45 to 0.49 and -6.57% CI95 -10 to -3.1, respectively). The risk of overweight/obesity was 3.5 times higher for patients with UC (OR=0.272, CI95 0.14-0.49, p=0.0004). CONCLUSIONS The prevalence of overweight and obesity in newly diagnosed children with IBD was 8.4% and was higher in patients with UC than in patients with CD. The results of this study have shown that not only malnourished children may suffer from IBD but also children who are overweight or obese at the time of diagnosis.

Value of Antral Nodularity for the Diagnosis of Helicobacter pylori Infection in Children

Background The aim of this study was to confirm the role of antral nodularity in the diagnosis of Helicobacter pylori (H. pylori) infection in children. Material/Methods This prospective study included 107 children (58 male; 54.2%), between the ages of 3 and 18 years, infected with H. pylori, which was confirmed if the patient had at least 2 of 4 positive test results (urea breath test, urease test in gastric biopsy, histopathology – positive hematoxylin and eosin and Giemsa staining, and/or monoclonal stool ELISA test – Amplified IDEIA™ Hp StAR™). The control group consisted of 234 children with abdominal pain, of similar age, in whom urease test in gastric tissue and histopathology were negative. In both groups, photographs of the gastric antrum taken during endoscopy were evaluated for nodularity by 3 independent endoscopists, blinded to the results of other tests. Sensitivity, specificity, and negative and positive predictive value of nodularity were assessed. Indication for upper endoscopy was chronic abdominal pain not considered to be functional. Results There were no statistical differences between groups regarding sex (chi-square test with Yates’s correction: p=0.8763) or age (mean ±SD) 11.77±3.49 and 12.43±3.32, study and control groups, respectively (Mann-Whitney test: p=0.1352). The sensitivity of the presence of nodularity as an indication of H. pylori infection was 91.6% and specificity was 91%. PPV of gastric nodularity was 81% and NPV was 96%. Conclusions Antral nodularity is reliable test. Physicians could start treatment of H. pylori infection whenever gastric nodularity is observed and the urease test result is positive, without waiting for histopathology results.

Metronidazole or Rifaximin for Treatment of Clostridium difficile in Pediatric Patients with Inflammatory Bowel Disease A Randomized Clinical Trial

Background: Interestingly, Clostridium difficile infection (CDI) worsens the course of inflammatory bowel disease (IBD); however, there is a paucity of data regarding the treatment of CDI in this group of patients. Methods: This was a prospective, single-blind trial. Children with flare of IBD and CDI were randomly assigned to receive metronidazole or rifaximin orally for 14 days. CDI was diagnosed based on a positive well-type enzyme immunoassay (EIA) toxins A/B stool test for C. difficile toxins A and/or B. The cure rate was defined as the percentage of patients with a negative EIA stool test for C. difficile toxins A/B measured 4 weeks after the end of treatment. Recurrence was defined as a repeat CDI within 2 to 8 weeks. Results: In total, we included 31 patients with IBD including 12 patients with Crohns disease and 19 with ulcerative colitis. Of them, 17 received metronidazole and 14 received rifaximin. There were no statistically significant differences between the 2 study groups including age, type of treatment, and disease activity. There was no statistically significant difference in the cure rate between patients treated with metronidazole and rifaximin (70.6% versus 78.6%, respectively, P = 0.5). We found no difference in recurrence rate between the 2 study treatment types (17% versus 0%, respectively, P = 0.3). We did not find an association between immunosuppressive therapy and CDI cure rate or CDI recurrence rate. Conclusions: Metronidazole and rifaximin were similarly effective treatments for CDI in pediatric patients with IBD.

Invasive Haemophilus influenzae Serotype f Case Reports in Mazovia Province, Poland.

Abstract After successful introduction of anti-Haemophilus influenzae (Hi) serotype b vaccination program in Poland, invasive non-b or nontypeable H. influenzae infections have been reported more frequently alike in other countries all over the world. In this paper, we report 2 cases of H. influenzae serotype f (Hif) meningitis with severe clinical presentations which are rarely seen in previously healthy children. The first case is a 6-year-old girl who was admitted to pediatric ward with signs of meningitis. Laboratory tests confirmed bacteremic meningitis caused by Hif. The girl responded very well to administered treatment and recovered without any further complications. No underlying comorbidities were found. The second patient was a 4-year-old boy who, in course of Hif bacteremic meningitis, developed rapid septicemia and, despite aggressive treatment, died within a few hours of hospitalization. The childs past history was unremarkable. By presenting these cases, we would like to remind clinicians that invasive non-b Hi infections can become fatal not only in the group of the youngest children or children with coexisting comorbidities, as most commonly reported in the worldwide literature. At the same time, we want to emphasize the legitimacy of constant monitoring Hi epidemiology in order to take accurate actions if necessary.