Induction of Remission in Pediatric Crohn’s Disease Patients Assessed by the Mucosal Inflammation Noninvasive Index

Mucosal healing (MH) is the main therapeutic goal of Crohn’s disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6–8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6–8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737–1.000) and 0.762 (95%CI: 0.570–0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.

Download Full-text

Exclusive Enteral Nutrition versus Infliximab in Inducing Therapy of Pediatric Crohn’s Disease

Gastroenterology Research and Practice ◽

10.1155/2017/6595048 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Youyou Luo ◽

Jindan Yu ◽

Jingan Lou ◽

Youhong Fang ◽

Jie Chen

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Effects ◽

Enteral Nutrition ◽

Clinical Symptoms ◽

Activity Index ◽

Group Versus ◽

Disease Activity Index ◽

Mucosal Healing ◽

Exclusive Enteral Nutrition

Aim. To compare the effectiveness of exclusive enteral nutrition (EEN) and infliximab (IFX) therapy in pediatric Crohn’s disease (CD). Methods. In a prospective study of children initiating EEN or infliximab therapy for CD, we compared clinical outcomes using the pediatric Crohn’s disease activity index (PCDAI), growth improvement, endoscopic mucosal healing, and adverse effects. Data were measured at baseline and after 8 weeks of therapy. Results. We enrolled 26 children with CD; of whom, 13 were treated with infliximab, 13 with EEN. Clinical response (PCDAI) reduction ≥ 15 or final PCDAI ≤ 10 was achieved by 83.3% in the EEN group and 90.9% in the IFX group. Body mass index for age (BMIFA) z-scores were significantly increased in both groups (P<0.05). No significant differences were observed in PCDAI, height for age (HFA), or BMI recovery between two groups. Adverse effects were detected in 30.7% on infliximab and 0% on EEN. Mucosal healing was achieved in 71.4% cases in the EEN group versus 85.7% in the IFX group. Conclusion. EEN provided similar improvements as IFX in clinical symptoms, mucosal healing, and BMI. EEN therapy has less adverse effects when compared with IFX. This trial is registered with the Clinical Registration Number: ChiCTR-OON-17010834.

Download Full-text

Effectiveness of Crohn’s Disease Exclusion Diet for Induction of Remission in Crohn’s Disease Adult Patients

Nutrients ◽

10.3390/nu13114112 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4112

Author(s):

Martyna Szczubełek ◽

Karolina Pomorska ◽

Monika Korólczyk-Kowalczyk ◽

Konrad Lewandowski ◽

Magdalena Kaniewska ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Activity Index ◽

Disease Activity Index ◽

Paediatric Population ◽

Adult Patients ◽

Exclusive Enteral Nutrition ◽

Inflammatory Bowel ◽

Exclusion Diet

Exclusive enteral nutrition (EEN) is a first-line treatment in active, mild to moderate Crohn’s disease (CD) in children. The Crohn’s disease exclusion diet (CDED), which avoids products known to have a pro-inflammatory effect on the intestinal mucosa, presents similar effectiveness to EEN for inducing remission in the paediatric population. The aim of the study was to evaluate the effectiveness of the CDED in inducing remission in adult patients. Between March 2020 and May 2021, 32 patients in a gastroenterology outpatient centre were treated according to the assumptions of the CDED. The patients were seen at baseline, at week 6, and at week 12 of the study. During the visits, anthropometric measurements and laboratory tests were performed, Crohn’s disease activity index (CDAI) was calculated, and the Inflammatory Bowel Disease Questionnaire (IBDQ) was completed. The study included a total of 32 participants, 18 women (56.3%) and 14 men (43.7%). Clinical remission was obtained in 76.7% patients after 6 weeks and in 82.1% after 12 weeks of therapy. Calprotectin levels were significantly lower in the second follow-up compared with baseline (p = 0.021). The CDED is an effective therapy for inducing remission in the adult CD population.

Download Full-text

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn’s Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa241 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ruben J Colman ◽

Yi-Ting Tsai ◽

Kimberly Jackson ◽

Brendan M Boyle ◽

Joshua D Noe ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Activity Index ◽

Disease Activity Index ◽

Mucosal Healing ◽

Mucosal Inflammation ◽

Operating Characteristics ◽

Cut Points ◽

Peripheral Blood Neutrophil ◽

Drug Concentrations

Abstract Background The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations. Methods We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn’s disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP <250 µg/g, with clinical response defined as a weighted Pediatric Crohn’s Disease Activity Index <12.5 or Δ>17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs). Results Among 56 CD patients, ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934, P < 0.001) and nCD64 <6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of >9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP <250 and FCP <100, respectively. We found patients achieving end of induction trough >5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels <5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031). Conclusions This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

Download Full-text

Magnetic resonance enterography, colonoscopy, and fecal calprotectin correlate in colonic Crohn’s disease

BMC Gastroenterology ◽

10.1186/s12876-019-1125-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Alexander S. Somwaru ◽

Vikesh Khanijow ◽

Venkat S. Katabathina

Keyword(s):

Crohn’S Disease ◽

Magnetic Resonance ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Clinical Results ◽

Fecal Calprotectin ◽

Magnetic Resonance Enterography ◽

Crohn’S Disease Activity

Abstract Background Fecal calprotectin (FCP), magnetic resonance enterography (MRE), and colonoscopy are complementary biometric tests that are used to assess patients with Crohn’s Disease (CD). While prior studies have evaluated the association between combinations of these tests, no study has established a correlation between all three: FCP, MRE, and colonoscopy. We prospectively investigated if there is correlation between these three tests, which may result in improved clinical outcomes that can then be used to streamline patient monitoring and treatment modification. Methods One hundred fifty-six patients with colonic CD were prospectively examined between March 2017 and December 2018. FCP levels, MRE, and colonoscopy were assessed in parallel on all 156 patients. Clinical CD activity was measured with the Crohn’s Disease Activity Index (CDAI). CD activity with FCP was measured with a quantitative immunoassay. CD activity on MRE was measured with the Magnetic Resonance Index of Activity (MaRIA). CD activity on colonoscopy was measured with the Crohn’s Disease Endoscopic Index of Severity (CDEIS). Results One hundred twelve patients (72%) had active disease (Crohn’s Disease Activity Index > 150) and 44 patients (28%) were in clinical remission disease (Crohn’s Disease Activity Index < 150). FCP levels, MaRIA, and CDEIS are highly correlated with positive and significant Pearson and Spearman coefficients, respectively (P < 0.0001), in univariate analyses. Regression analysis (multivariate analyses) demonstrates significant, positive correlation between FCP and MaRIA (r = 1.07, P < 0.0001) and between FCP and CDEIS (r = 0.71, P = 0.03), and between. MaRIA and CDEIS (r = 0.63, P = 0.01). Conclusions FCP levels significantly correlate with the degree of active inflammation in patients with colonic Crohn’s Disease. Improved clinical results may be achieved by using a biometric strategy that incorporates FCP, colonoscopy, and MRE together. This strategy may in-turn be used in the future to streamline monitoring disease activity and adjustment of therapy to improve long term patient outcomes.

Download Full-text

Role of MR Enterography in Evaluation of Disease Activity in Pediatric Crohn’s Disease: Correlation between MR Enterography and Pediatric Crohn’s Disease Activity Index Scores

Journal of Gastrointestinal and Abdominal Radiology ◽

10.1055/s-0040-1701328 ◽

2020 ◽

Vol 03 (02) ◽

pp. 118-125

Author(s):

Shilpa Radhakrishnan ◽

Amarnath Chellathurai ◽

Srinivas Sankaranrayanan ◽

Dharani Sankar ◽

Suja Rajan

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Mr Enterography ◽

Clinical Activity ◽

Positive Correlation

Abstract Objectives The aim of the study was to assess the role of MR Enterography (MRE) in the diagnosis and follow-up of children with Crohn’s disease (CD) and to correlate disease activity indices with known MRE features of active disease. Methods This was a retrospective study including 24 patients (median age 11 years, 17 males) with clinically and histologically proven CD who underwent MRE. Two previously validated MRE scores—Magnetic Resonance Enterography Global Score (MEGS) and CD MRI index (CDMI)—were calculated. A correlative analysis was made between the Pediatric Crohn’s Disease Activity Index (PCDAI) score and MRE scores as well as individually with each MR variable. Comparison of both the MR scores was made between patients with different disease activity. Results MEGS and PCDAI scores showed strong positive correlation (r = 0.724, p = < 0.001); CDMI and PCDAI scores showed moderate positive correlation (r = 0.661, p = 0.0004). There was statistically significant difference in the MR scores between patients grouped by clinical activity. Among individual MR variables, mural thickness and enhancement best predicted the disease activity. Conclusions MRE-based scores and findings correlate with clinical activity in pediatric CD. Thereby, MRE can be considered a valuable tool in the management of CD, predicting disease activity and offering a potential alternative to endoscopy in monitoring patients during follow-up.

Download Full-text

Bovine lactoferrin and Crohn’s disease: a case study

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0107 ◽

2017 ◽

Vol 95 (1) ◽

pp. 133-141 ◽

Cited By ~ 4

Author(s):

David B. Alexander ◽

Masaaki Iigo ◽

Mohamed Abdelgied ◽

Keiji Ozeki ◽

Satoshi Tanida ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Activity Index ◽

Disease Activity Index ◽

Disease Recurrence ◽

Mucosal Healing ◽

University Hospital ◽

Bovine Lactoferrin ◽

Colonoscopic Examination

A 22-year-old male suffering from abdominal pain, repeated diarrhea, and weight loss visited the Digestive Disease Department of Nagoya City University Hospital on 19 December 2011. He was hospitalized and diagnosed with Crohn’s colitis. His Crohn’s Disease Activity Index (CDAI) was 415. Treatment by granulocyte apheresis, mesalazine, and adalimumab was started. His CDAI was 314 on 30 December and 215 on 5 January. A colonoscopic examination on 19 January showed almost complete remission in the transverse colon and marked remission in the rectum. Mesalazine therapy was stopped on 28 February, and the patient was instructed to self-inject 40 mg of adalimumab every other week. His CDAI was 50 on 10 April, indicating clinical remission. His last self-injection of adalimumab was on 24 April 2012, and he started taking 1 g of bovine lactoferrin (bLF) daily. His CDAI was 35 on 8 January 2013. He continued taking 1 g of bLF daily without any other treatment for Crohn’s disease. Laboratory blood tests on 7 September 2015 showed no sign of disease recurrence, and a colonoscopic examination on 23 October 2015 showed almost complete mucosal healing. This case indicates that ingestion of bLF to maintain Crohn’s disease in a remissive state should be further explored.

Download Full-text

The Association Between Genetic Variants, Pharmacokinetics, and Infliximab Efficacy in Pediatric Patients With Crohn's Disease in China

Frontiers in Pediatrics ◽

10.3389/fped.2021.744599 ◽

2021 ◽

Vol 9 ◽

Author(s):

Wenhui Hu ◽

Yan Feng ◽

Ziqing Ye ◽

Zifei Tang ◽

Lai Qian ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Genetic Variants ◽

Pediatric Patients ◽

Activity Index ◽

Area Under The Curve ◽

Disease Activity Index ◽

Threshold Level ◽

Mucosal Healing ◽

Nucleotide Polymorphisms

Background: Infliximab is an effective therapy for Crohn's disease (CD). Early non-invasive predictors of disease remission allow for modification of treatments. The aim of this study was to investigate the associations between genetic variants, pharmacokinetics, and infliximab efficacy in pediatric patients with CD.Methods: This retrospective observational study included CD patients under infliximab therapy between August 2015 and December 2020. Information on demographics, laboratory tests, medication data, and disease activity index was collected. The trough levels of infliximab (TLI) and antibodies to infliximab (ATI) were measured at week 14, and reactive drug monitoring was performed during follow-up. Ten single-nucleotide polymorphisms involved in the NF-κB-mediated inflammatory response, pharmacokinetics, and therapeutic response to infliximab were genotyped.Results: A total of 62 pediatric CD patients were enrolled. The clinical remission (CR) rate was 69.4 and 63.2% at week 14 and week 30, respectively. TLI at week 14 was significantly independently associated with CR at week 14 and mucosal healing (MH) at week 30 (p = 0.007 and p = 0.025, respectively). The optimal TLI threshold level capable of distinguishing between the CR and non-CR groups was 2.62 μg/ml (p < 0.001, area under the curve = 0.79, sensitivity = 69.2%, specificity = 78.9%), while that capable of distinguishing between the MH and non-MH groups was 3.34 μg/ml (p < 0.001, area under the curve = 0.85, sensitivity = 78.6%, specificity = 79.4%). Rs3397 in TNFRSF1B was associated with time to ATI production in CD patients (p < 0.001).Conclusions: Higher TLI contributed to achieving MH. Genotyping rs3397 in TNFRSF1B may identify patients who are prone to generating immunogenicity to drugs.

Download Full-text

Magnetic Resonance Enterography, Colonoscopy, and Fecal Calprotectin correlate in colonic Crohn’s Disease

10.21203/rs.2.13286/v1 ◽

2019 ◽

Author(s):

Alexander Stephen Somwaru ◽

Vikesh Khanijow ◽

Venkat Katabathina

Keyword(s):

Crohn’S Disease ◽

Magnetic Resonance ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Clinical Results ◽

Fecal Calprotectin ◽

Magnetic Resonance Enterography ◽

Crohn’S Disease Activity

Abstract Background Fecal calprotectin (FCP), magnetic resonance enterography (MRE), and colonoscopy are complementary biometric tests that are used to assess patients with Crohn’s Disease (CD). While prior studies have evaluated the association between combinations of two of these tests or surgical specimens, no study has established a correlation between all three: FCP, MRE, and colonoscopy. We investigated if the correlation between these three tests may result in improved clinical outcomes that can then be used to streamline patient monitoring and treatment modification. Methods 156 patients with colonic CD were examined between March 2017 and December 2018. FCP levels, MRE, and colonoscopy were assessed in parallel on all 156 patients. Clinical CD activity was measured with the Crohn’s Disease Activity Index (CDAI). CD activity with FCP was measured with a quantitative immunoassay. CD activity on MRE was measured with the Magnetic Resonance Index of Activity (MaRIA). CD activity on colonoscopy was measured with the Crohn’s Disease Endoscopic Index of Severity (CDEIS). Results 112 patients (72%) had active disease (Crohn’s Disease Activity Index > 150) and 44 patients (28%) were in clinical remission disease (Crohn’s Disease Activity Index < 150). FCP levels, MaRIA, and CDEIS are highly correlated with positive and significant Pearson and Spearman coefficients, respectively (P < 0.0001), in univariate analyses. Regression analysis (multivariate analyses) demonstrates significant, positive correlation between FCP and MaRIA (r = 1.07, P < 0.0001) and between FCP and CDEIS (r = 0.71, P = 0.03), and between MaRIA and CDEIS (r = 0.63, P = 0.01). Conclusions FCP levels significantly correlate with the degree of active inflammation in patients with colonic Crohn’s Disease. Improved clinical results may be achieved by using a biometric strategy that incorporates FCP, colonoscopy, and MRE together. This strategy may in-turn be used in the future to streamline monitoring disease activity and adjustment of therapy to improve long term patient outcomes.

Download Full-text

Magnetic Resonance Enterography, Colonoscopy, and Fecal Calprotectin correlate in colonic Crohn’s Disease

10.21203/rs.2.13286/v4 ◽

2019 ◽

Author(s):

Alexander S. Somwaru ◽

Vikesh Khanijow ◽

Venkat S. Katabathina

Keyword(s):

Crohn’S Disease ◽

Magnetic Resonance ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Clinical Results ◽

Fecal Calprotectin ◽

Magnetic Resonance Enterography ◽

Crohn’S Disease Activity

Abstract Background: Fecal calprotectin (FCP), magnetic resonance enterography (MRE), and colonoscopy are complementary biometric tests that are used to assess patients with Crohn’s Disease (CD). While prior studies have evaluated the association between combinations of these tests, no study has established a correlation between all three: FCP, MRE, and colonoscopy. We prospectively investigated if there is correlation between these three tests, which may result in improved clinical outcomes that can then be used to streamline patient monitoring and treatment modification. Methods: 156 patients with colonic CD were prospectively examined between March 2017 and December 2018. FCP levels, MRE, and colonoscopy were assessed in parallel on all 156 patients. Clinical CD activity was measured with the Crohn’s Disease Activity Index (CDAI). CD activity with FCP was measured with a quantitative immunoassay. CD activity on MRE was measured with the Magnetic Resonance Index of Activity (MaRIA). CD activity on colonoscopy was measured with the Crohn’s Disease Endoscopic Index of Severity (CDEIS). Results: 112 patients (72%) had active disease (Crohn’s Disease Activity Index > 150) and 44 patients (28%) were in clinical remission disease (Crohn’s Disease Activity Index < 150). FCP levels, MaRIA, and CDEIS are highly correlated with positive and significant Pearson and Spearman coefficients, respectively (P < 0.0001), in univariate analyses. Regression analysis (multivariate analyses) demonstrates significant, positive correlation between FCP and MaRIA (r = 1.07, P < 0.0001) and between FCP and CDEIS (r = 0.71, P = 0.03), and between MaRIA and CDEIS (r = 0.63, P = 0.01). Conclusions: FCP levels significantly correlate with the degree of active inflammation in patients with colonic Crohn’s Disease. Improved clinical results may be achieved by using a biometric strategy that incorporates FCP, colonoscopy, and MRE together. This strategy may in-turn be used in the future to streamline monitoring disease activity and adjustment of therapy to improve long term patient outcomes.

Download Full-text