Kristyna Zarubova

Disease activity is an important factor for indeterminate interferon-γ release assay results in children with inflammatory bowel disease.

Background: Interferon-&ggr; release assay (IGRA) is widely used for screening of latent tuberculosis (TB) before and during biological therapy (BT). An indeterminate result of IGRA represents a limitation in the management of inflammatory bowel disease (IBD). Data on factors influencing IGRA results are scarce in children. The aim of the study was to identify factors influencing IGRA results in children with IBD. Methods: Seventy-two children with IBD (59 Crohn disease, 11 ulcerative colitis, 2 IBD-unclassified) indicated for BT were tested for TB infection (history, TB skin test, chest radiograph, IGRA; QuantiFERON—TB Gold in tube [QFT]) and consecutively retested using QFT in 1-year intervals. Results: We recorded 165 results of QFT (3% positive, 87% negative, and 10% indeterminate results). During follow-up we identified 4 conversions of negative QFT to positivity (3%) and 4 reversions (4%). Patients with indeterminate results of QFT had significantly lower actual weight-for-height z score (P = 0.022), higher platelet count (P = 0.00017), and lower levels of serum albumin (P = 0.015) compared with patients with positive or negative QFT. Indeterminate QFT was associated with corticosteroid treatment, BT, and disease activity, but not with treatment by immunomodulators. In a subanalysis of patients with Crohn disease alone, Pediatric Crohns Disease Activity Index was identified as single independent risk factor for indeterminate results (P = 0.00037). Conclusions: Although corticosteroid treatment is traditionally considered to be the main risk factor for indeterminate results of IGRA, the disease activity of IBD has even more profound effects on the results.

Supplementation with 2000 Iu of Cholecalciferol Is Associated with Improvement of Trabecular Bone Mineral Density and Muscle Power in Pediatric Patients with Ibd

Background: Inflammatory bowel diseases (IBD) are associated with altered bone health and increased risk for fractures. Vitamin D deficiency is frequently found in IBD; however, the effect of vitamin D supplementation on bone health of children with IBD is poorly understood. We aimed to observe the changes in volumetric bone density and dynamic muscle functions after vitamin D substitution in a cohort of pediatric patients with IBD. Methods: This was a prospective observational study of 55 patients (aged 5–19 years) with IBD. Bone quality was assessed using peripheral quantitative computed tomography and muscle functions by jumping mechanography at baseline and after a median of 13.8 (interquartile range, 12.0–16.0) months of daily substitution of 2000 IU of cholecalciferol. Results: Median serum levels of 25-hydroxyvitamin D increased from 58 nmol/L at the baseline visit to 85 nmol/L at the last follow-up visit (P < 0.001); no signs of overdose were reported. The Z-scores of trabecular bone mineral density, cortical bone cross-sectional area, and maximal muscle power improved significantly during the follow-up period (+0.5, P = 0.001, +0.3, P = 0.002 and +0.5, P = 0.002, respectively). Cholecalciferol substitution was positively associated with trabecular bone mineral density and maximal muscle power (estimates 0.26, 95% confidence interval 0.14–0.37, P < 0.0001 and 0.60, 95% confidence interval 0.32–0.85, P < 0.0001, respectively) but not with the Strength–Strain Index or maximal muscle force (Fmax). Conclusions: We observed an improvement in bone and muscle parameters after cholecalciferol substitution in pediatric patients with IBD. Therefore, vitamin D substitution can be considered in such patients.

Anti-TNFα Treatment After Surgical Resection for Crohnʼs Disease Is Effective Despite Previous Pharmacodynamic Failure

BACKGROUND The outcome of patients with Crohns disease who failed anti-tumor necrosis factor alpha (anti-TNFα) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNFα agent postoperatively. METHODS Pediatric patients with Crohns disease who underwent intestinal resection and were treated with anti-TNFα agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNFα pharmacodynamic failure and those with no preoperative anti-TNFα treatment. RESULTS A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNFα initiation was 8 months (interquartile range 4-14 months). At the time of postoperative anti-TNFα initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNFα treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNFα treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNFα treatment. CONCLUSIONS Pediatric patients with Crohns disease who failed anti-TNFα therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNFα naive patients.Background: The outcome of patients with Crohns disease who failed anti-tumor necrosis factor alpha (anti-TNF&agr;) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNF&agr; agent postoperatively. Methods: Pediatric patients with Crohns disease who underwent intestinal resection and were treated with anti-TNF&agr; agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNF&agr; pharmacodynamic failure and those with no preoperative anti-TNF&agr; treatment. Results: A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNF&agr; initiation was 8 months (interquartile range 4–14 months). At the time of postoperative anti-TNF&agr; initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNF&agr; treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1–2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNF&agr; treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNF&agr; treatment. Conclusions: Pediatric patients with Crohns disease who failed anti-TNF&agr; therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNF&agr; naive patients.

Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors

Background: In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohns disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. Summary: Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.

Correction to: Fecal calprotectin is not a clinically useful marker for the prediction of the early nonresponse to exclusive enteral nutrition in pediatric patients with Crohn disease

This article was originally published with all author names incorrectly listed. All author names have now been transposed and appear correctly above. The original article was corrected.