Actual Anti-TNF Trough Levels Relate to Serum IL-10 in Drug-Responding Patients With Crohn’s Disease

Abstract Background Patients with Crohn’s disease (CD) responding to anti–tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. Methods Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes’ genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. Results One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn’s Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). Conclusion Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.

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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.

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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.

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

Journal of Clinical Medicine ◽

10.3390/jcm10235613 ◽

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.

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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.

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Lewis Score Correlates More Closely with Fecal Calprotectin Than Capsule Endoscopy Crohn’s Disease Activity Index

Digestive Diseases and Sciences ◽

10.1007/s10620-011-1956-8 ◽

2011 ◽

Vol 57 (4) ◽

pp. 987-993 ◽

Cited By ~ 60

Author(s):

Anastasios Koulaouzidis ◽

Sarah Douglas ◽

John N. Plevris

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Capsule Endoscopy ◽

Activity Index ◽

Disease Activity Index ◽

Fecal Calprotectin ◽

Crohn’S Disease Activity

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

10.21203/rs.2.13286/v3 ◽

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

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Calprotectin Is a Useful Tool in Distinguishing Coexisting Irritable Bowel-Like Symptoms from That of Occult Inflammation among Inflammatory Bowel Disease Patients in Remission

Gastroenterology Research and Practice ◽

10.1155/2013/620707 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 27

Author(s):

Lars-Petter Jelsness-Jørgensen ◽

Tomm Bernklev ◽

Bjørn Moum

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Activity Index ◽

Disease Activity Index ◽

Fecal Calprotectin ◽

Elisa Test ◽

Rome Ii Criteria ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Irritable Bowel

Background and Aim. In the inflammatory bowel diseases (IBDs), many symptoms are similar to the functional disorder irritable bowel syndrome (IBS). A challenge is thus to distinguish symptoms of IBD from IBS. The aim of this study was to investigate the levels of calprotectin in IBS-positive IBD patients in remission.Methods. Remission was defined as a simple clinical colitis activity index (SCCAI) or simple crohn’s disease activity index (SCDAI) score of less than three and less than four, respectively. The Rome II criteria were used to identify cases, and the calprotectin ELISA test was used to quantify calprotectin in stools.Results. The Rome II criteria were fulfilled in 24.6% of ulcerative colitis (UC) patients, while the comparable number for Crohn's disease (CD) was 21.4%. There was a tendency for elevated fecal calprotectin levels in IBS-positive patients, regardless of diagnosis. However, these differences were only significant in CD.Conclusions. Calprotectin levels are elevated in subgroups of IBD patients that are in remission and have coexisting IBS-like symptoms. This study underscores the clinical usefulness of a noninvasive marker to distinguish patients in need of intensified followup from those that do not need further workup.

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

10.21203/rs.2.13286/v2 ◽

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 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.

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Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab045 ◽

2021 ◽

Author(s):

Neeraj Narula ◽

Emily C L Wong ◽

Parambir S Dulai ◽

John K Marshall ◽

Jean-Frederic Colombel ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Activity Index ◽

Disease Activity Index ◽

Symptom Improvement ◽

Logistic Regression Models ◽

Post Hoc Analysis ◽

Endoscopic Remission ◽

Post Hoc ◽

The Impact

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] <150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score <3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.

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