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1.
Dig Dis ; 36(1): 40-48, 2018.
Article in English | MEDLINE | ID: mdl-28817809

ABSTRACT

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 Crohn's 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.


Subject(s)
Crohn Disease/drug therapy , Infliximab/therapeutic use , Adolescent , Area Under Curve , Biomarkers/metabolism , Blood Sedimentation , C-Reactive Protein/metabolism , Child , Crohn Disease/blood , Feces/chemistry , Female , Humans , Inflammation/pathology , Infliximab/administration & dosage , Leukocyte L1 Antigen Complex/metabolism , Male , ROC Curve , Remission Induction , Treatment Failure
2.
J Pediatr Gastroenterol Nutr ; 58(3): 320-4, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24126833

ABSTRACT

BACKGROUND: Interferon-γ 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 Crohn's 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.


Subject(s)
Inflammatory Bowel Diseases/complications , Interferon-gamma Release Tests , Interferon-gamma/metabolism , Latent Tuberculosis/diagnosis , Tuberculin Test , Adolescent , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Body Weight , Child , Colitis, Ulcerative/complications , Colitis, Ulcerative/pathology , Crohn Disease/complications , Crohn Disease/pathology , Female , Humans , Inflammatory Bowel Diseases/pathology , Latent Tuberculosis/complications , Latent Tuberculosis/metabolism , Male , Platelet Count , Risk Factors , Serum Albumin/metabolism
3.
Clin Lab ; 60(12): 1993-2000, 2014.
Article in English | MEDLINE | ID: mdl-25651733

ABSTRACT

BACKGROUND: Children with suspected bowel inflammation require an invasive endoscopic procedure, which is usually performed under general anesthesia. To improve the selection of candidates for endoscopy, fecal calprotectin level has been proposed as a noninvasive marker of intestinal inflammation. In the future, home testing is a likely option. Thus, the aim of this study was to affirm the association between bedside-measured fecal calprotectin concentration and histological and endoscopic findings in a panel of patients with suspected chronic bowel inflammation. METHODS: Stool samples and microscopic and macroscopic findings from 41 patients, who underwent ileocolonoscopy for suspicion of bowel inflammation, were consecutively obtained between April 2009 and December 2010. Stool samples were analyzed using the bedside fecal calprotectin enzyme-linked immunosorbent assay (Quantum Blue; Bühlmann, Laboratories AG, Switzerland). RESULTS: Fecal calprotectin levels were elevated in 18 children with bowel inflammation on endoscopy (median at the upper limit of undiluted samples, 300 µg/g) compared with 23 children without bowel inflammation (median, 105 µg/g; p < 0.00097). Similarly, the fecal calprotectin level was elevated in 25 children with positive histological findings as assessed by a pathologist (median, 300 µg/g) compared with 16 children without histological inflammation (median, 73 µg/g; p < 0.000014). Based on the optimal area under the curve, we calculated the cutoff fecal calprotectin level for bowel inflammation on endoscopy as 167 µg/g (area under the curve, 0.86; 95% confidence interval (CI), 0.81 - 0.92) and on histological examination as 280 µg/g (area under the curve, 0.78; 95% CI, 0.70 - 0.86). Fecal calprotectin level was more sensitive than endoscopy for diagnosis of microscopic bowel inflammation (p = 0.000014). CONCLUSIONS: Our results clearly show that even the bedside test for fecal calprotectin level, using the optimal cut-off value, is feasible enough in determining candidates for an endoscopic procedure in order to confirm bowel inflammation and is more tightly associated with histological findings than with endoscopic findings. Thus, the calprotectin level reflects histological activity, even in cases with normal endoscopic findings. The bedside test described herein is a sufficient screening method for this purpose.


Subject(s)
Colon , Colonoscopy , Feces/chemistry , Ileum , Inflammation Mediators/analysis , Inflammatory Bowel Diseases/diagnosis , Leukocyte L1 Antigen Complex/analysis , Point-of-Care Systems , Adolescent , Age Factors , Area Under Curve , Biomarkers/analysis , Case-Control Studies , Child , Child, Preschool , Colon/chemistry , Colon/immunology , Colon/pathology , Feasibility Studies , Female , Humans , Ileum/chemistry , Ileum/immunology , Ileum/pathology , Inflammatory Bowel Diseases/blood , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/pathology , Male , Predictive Value of Tests , ROC Curve , Up-Regulation
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