Association of Early Postinduction Adalimumab Exposure With Subsequent Clinical and Biomarker Remission in Children with Crohn’s Disease

2020 ◽  
Author(s):  
Firas Rinawi ◽  
Amanda Ricciuto ◽  
Peter C Church ◽  
Karen Frost ◽  
Eileen Crowley ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Primary Outcome ◽  
Activity Index ◽  
Area Under The Curve ◽  
Positive Likelihood Ratio ◽  
Fecal Calprotectin ◽  
Clinical Biomarker ◽  
Objective Outcomes ◽  
Trough Levels

Abstract Background Data on the association between early postinduction serum adalimumab (ADA) trough levels (TLs) and objective outcomes are scarce. The aim of this study was to investigate whether early ADA TLs at weeks 4 and 8 are associated with clinical and biomarker remission at week 24 in pediatric Crohn’s disease (CD). Methods Adalimumab TLs at weeks 4 and 8 were prospectively measured in anti-TNF-naïve children initiating treatment with ADA monotherapy for luminal inflammatory CD. The primary outcome was combined clinical and biomarker remission at week 24, defined as achieving steroid-free clinical remission (Pediatric CD activity index <10) and biomarker remission (fecal calprotectin <250 µg/g and CRP <5 µg/mL). Results Among 65 patients, 39 (60%) achieved combined clinical/biomarker remission at week 24 without dose escalation. Adalimumab TLs at both weeks 4 and 8 were significantly higher in remitters vs nonremitters at week 24 (P < 0.001 and P = 0.002, respectively). Adalimumab levels at weeks 4 and 8 were good predictors of combined clinical/biomarker remission at week 24 (area under the curve, 0.887, 95% CI, 0.798–0.942; and area under the curve, 0.761, 95% CI, 0.632–0.899, respectively). The best ADA TL cutoffs at weeks 4 and 8 for predicting clinical/biomarker remission at week 24 were 22.5 µg/mL (80% sensitivity, 90% specificity, positive likelihood ratio [LR+] 8.0, negative LR [LR-] 0.2) and 12.5 µg/mL (94% sensitivity, 60% specificity, LR+ 2.4, LR- 0.1), respectively. Higher induction doses per m2 correlated positively with TLs at weeks 4 and 8. Conclusion Greater early ADA exposure is associated with superior clinical/biomarker outcomes at week 24.

scholarly journals DOP12 Validation of a modified simple ultrasound activity Score for children with Crohn’s Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S050-S051
Author(s):  
H Ma ◽  
D M Isaac ◽  
A Petrova ◽  
P Almeida ◽  
D Parsons ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Fecal Calprotectin ◽  
Activity Score ◽  
Chi Square ◽  
Minimal Invasiveness ◽  
Reactive Protein

Abstract Background Transabdominal bowel ultrasound (TABUS) is an ideal tool to assess the bowel wall thickness (BWT) of children with Crohn’s disease (CD) due to its minimal invasiveness. Recently the Simple Ultrasound Activity Score for CD (SUS-CD) was developed and validated in adults using the Simple Endoscopic Score for CD (SES-CD). Our aim was to determine how the SUS-CD performed in children at diagnosis in comparison to endoscopy. Methods Pediatric patients (0–18 years old) with suspected inflammatory bowel disease (IBD) were prospectively enrolled through the Edmonton Pediatric IBD Clinic in Alberta, Canada. Patients underwent a baseline TABUS to visualize the intestine (excluding rectum, which is difficult to see with TABUS), blood work and endoscopy. The weighted pediatric CD activity index (wPCDAI) assessed disease activity, and SES-CD assessed endoscopic disease. Modified SUS-CD (excluding rectal sub score) was calculated using BWT scores (0=<3mm, 1=3–4.9mm, 2=5–7.9mm, 3=>8mm) and colour doppler scores (0=no or 1 vessel, 1=2–5 vessels, 2=>5 vessels per cm2) for each segment (terminal ileum, right colon, transverse colon, left colon) and compared to SES-CD. Modified SUS-CD was correlated to wPCDAI score, C-reactive protein (CRP) and fecal calprotectin (FCP). Using SPSS, anova and Chi square were used to assess for an association between TABUS parameters and wPCDAI. Spearman’s rank (rho) and Pearson’s correlation (r) were used to assess for a correlation between modified SUS-CD with SES-CD, wPCDAI, CRP and FCP. Results 40 patients recruited, 35 had CD (mean age 12.6(2.85)) and 5 were normal and scanned for suspected IBD (mean age 12.2(3.75)). Median wPCDAI and SES-CD scores for CD patients were 61(IQR 35.6–77.5) and 15(IQR 7.5–21) respectively. Fat proliferation was associated with severe CD based on wPCDAI (p<0.05). The modified SUS-CD score correlated well with the modified SES-CD score (rho=0.79,r=0.76,p<0.001,R2 linear=0.465). When the BWT threshold was lowered by 0.5mm for each BWT category, correlation improved (rho=0.80,r=0.82,p<0.001,R2 Linear=0.541). Using a similar lower threshold for BWT, a receiver operating characteristic curve analysis revealed an area under the curve of 0.87 and 0.90 for detecting mild endoscopic activity and moderate endoscopic activity, respectively. There was a significant correlation between SUS-CD and wPCDAI score (r=0.56,p<0.01), CRP (r=0.55,p<0.01) and FCP (r=0.56,p<0.01). Conclusion Fat proliferation was associated with more severe CD. The modified SUS-CD correlated well with modified SES-CD score, wPCDAI, CRP and FCP. Correlation improved when BWT threshold in each category was dropped by 0.5mm. These data support the use of TABUS as an effective adjunct to the assessment of pediatric CD.

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

2019 ◽  
Vol 19 (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.

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

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.

scholarly journals Serum MMP-9: a novel biomarker for prediction of clinical relapse in patients with quiescent Crohn’s disease, a post hoc analysis

2019 ◽  
Vol 12 ◽  
pp. 175628481988159 ◽  
Author(s):  
Doron Yablecovitch ◽  
Uri Kopylov ◽  
Adi Lahat ◽  
Michal M. Amitai ◽  
Eyal Klang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Area Under The Curve ◽  
Fecal Calprotectin ◽  
Clinical Relapse ◽  
Post Hoc Analysis ◽  
Reactive Protein ◽  
Increased Risk ◽  
Post Hoc

Background: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn’s disease (CD). Methods: This study was a post hoc analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period. Serial C-reactive protein (CRP) and fecal calprotectin (FC) levels were measured, and the patients underwent repeated capsule endoscopies (CEs) every 6 months. Small bowel inflammation was quantified by Lewis score (LS) for CE. A baseline magnetic resonance enterography was also performed, and MaRIA score was calculated. Serum MMP-9 levels in baseline blood samples were quantified by ELISA. Results: Out of 58 eligible enrolled patients, 16 had a flare. Higher levels of baseline MMP-9 were found in patients who developed subsequent symptomatic flare compared with patients who did not [median 661 ng/ml, 25–75 interquartile range (IQR; 478.2–1441.3) versus 525.5 ng/ ml (339–662.7), respectively, p = 0.01]. Patients with serum MMP-9 levels of 945 ng/ ml or higher were at increased risk for relapse within 24 months [area under the curve (AUC) of 0.72 [95% confidence interval (CI): 0.56–0.88]; hazard ratio 8.1 (95% CI 3.0–21.9, p < 0.001)]. Serum MMP-9 concentrations showed weak and moderate correlation to baseline LS and FC, respectively ( r = 0.31, p = 0.02; r = 0.46, p < 0.001). No correlation was found between serum MMP-9 to CRP and MaRIA score. Conclusions: Serum MMP-9 may be a promising biomarker for prediction of clinical flare in CD patients with quiescent disease.

scholarly journals Oral 5-Aminosalicyclic Acid Versus 6-Methylprednisolone in Active Crohn's Disease

1990 ◽  
Vol 4 (7) ◽  
pp. 446-451 ◽  
Author(s):  
Jürgen Schölmerich ◽  
Harro Jenss ◽  
Franz Hartmann ◽  
Hanne Döpfer ◽  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Area Under The Curve ◽  
Disease Activity Index ◽  
Entrance Examination ◽  
Aminosalicylic Acid ◽  
Double Blind ◽  
Treatment Groups ◽  
Starting Dose

The response to 5-aminosalicylic acid (5-ASA) in active Crohn's disease was studied in comparison to methylprednisolone in a 24 week randomized double-blind multicentre study. Sixty-two patients were included in the analysis. Thirty were treated with 500 mg 5-ASA qid and 32 with methylprednisolone (starting dose 48 mg for one week, then reduced weekly to 32, 24, 20, 16 and 12 mg with maintenance at 8 mg/day for the remaining 18 weeks). Mean age, earlier surgical intervention, localization of Crohn's disease and extraintestinal manifestations were not different in both groups. The Crohn's disease activity index (CDAI) and the van Hees index were not significantly different in both treatment groups at the entrance examination (median CDAI 232 in the 5-ASA group and 220 in the methylprednisolone group). According to the protocol, treatment was stopped due to insufficient efficacy in 73% of the patients receiving 5-ASA and in 34% of the patients receiving methylprednisolone (x2test P=0.0019). The area under the curve for the CDAl was significantly greater in 5-ASA (median 170) than in methylprednisolone (P≤0.007) (68). Eleven per cent of patients taking 5-ASA and 26% of patients taking methylprednisolone presented relevant side effects to treatment (not significant). It is concluded from these data that 5-ASA at the dose used in this study is not efficient in the treatment of active Crohn's disease. Considering recent studies in ulcerative colitis, a trial using a higher dose is indicated.

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

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 &lt; 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 &lt; 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 &lt; 0.001).Conclusions: Higher TLI contributed to achieving MH. Genotyping rs3397 in TNFRSF1B may identify patients who are prone to generating immunogenicity to drugs.

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

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.

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

2021 ◽  
Vol 10 (23) ◽  
pp. 5613
Author(s):  
Roma Herman ◽  
Paulina Dumnicka ◽  
Stanisław Pieczarkowski ◽  
Krzysztof Fyderek
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Induction Therapy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Mucosal Inflammation ◽  
Exclusive Enteral Nutrition

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.

scholarly journals Peripheral Blood Inflammatory Markers and Crohn’s Disease: Lymphocytes Counts Could Predict Stricture Lesions 

2020 ◽  
Author(s):  
Juanjuan Zhang ◽  
Zhen Guo ◽  
Yanqing Diao ◽  
Binlin Da ◽  
Zhiming Wang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Peripheral Blood ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Area Under The Curve ◽  
Full Blood Count ◽  
Intestinal Fibrosis ◽  
Jinling Hospital ◽  
Single Balloon

Abstract Background: Intestinal stricture is a complication of Crohn’s disease (CD) due to fibrosis, but there are no biomarkers for predicting intestinal strictures before clinical obstruction. It is reported that several types of lymphocytes (LC) are involved in the pathogenesis of intestinal fibrosis. However, few studies have focused on the peripheral blood LC in patients with CD associated stricture.Aim：To analyze the relationships between peripheral blood inflammatory markers especially LC and CD to provide evidence for CD diagnosis and therapy. Methods: A total of 158 CD patients who underwent single-balloon enteroscopy from January 2016 to June 2019 in Jinling Hospital were retrospectively enrolled. The Montreal classification, maintenance medicines, CD activity index (CDAI), simple endoscopic score for CD (SES-CD), full blood count and C-reactive protein (CRP) level were recorded. The relationships among peripheral blood inflammatory markers, disease activity and intestinal strictures were analyzed using SPSS 22.0. Results: After excluding 8 patients treated with azathioprine, which severely affects blood counts, 150 patients were divided into two groups: a stricture group (n=82) and non-stricture group (n=68). LC and the proportion of lymphocytes (LC%) were significantly lower in the stricture group than in the non-stricture group, p was 0.000 and 0.018, respectively, and LC was an independent risk factor of stricture lesion. In the subgroup analysis, 30 strictures without obstruction were classified as mild strictures, and 52 cases of obstruction were in the severe stricture group. LC notably decreased following stricture aggravation, p=0.000. The area under the curve (AUC) of LC predicting strictures was 0.711 with sensitivity of 73.5% and a specificity of 63.4% (cutoff: 1.245). Conclusion: LC gradually decreases as intestinal strictures aggravated and could be a new marker for predicting intestinal strictures in CD patients.

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