scholarly journals Vedolizumab Tissue Concentration Correlates to Mucosal Inflammation and Objective Treatment Response in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Renske W M Pauwels ◽  
Elisa Proietti ◽  
Christien J van der Woude ◽  
Lindsey Oudijk ◽  
Marie-Rose B S Crombag ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Treatment Response ◽  
Bowel Disease ◽  
Serum Levels ◽  
Mucosal Inflammation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Intestinal Tissue ◽  
Tissue Levels ◽  
Inflammatory Bowel

Abstract Background The association between vedolizumab (VDZ) exposure and treatment response is unclear and seems insufficiently explained by serum levels. The aim of this study was to assess the correlation between VDZ concentrations in serum and intestinal tissue and their association with mucosal inflammation and response to VDZ. Methods This prospective study included 37 adult patients with inflammatory bowel disease with endoscopic inflammation at baseline who started VDZ. At week 16, serum and biopsies were collected for VDZ measurement by enzyme-linked immunosorbent assay. Nonlinear mixed-effects modeling was used to calculate serum trough concentrations and to assess intestinal tissue concentrations. Validated clinical and endoscopic scores were used to define clinical and endoscopic response and remission, and fecal calprotectin levels were used to assess biochemical response. Histologic remission was determined by the Nancy score. Results A positive correlation was observed between VDZ concentrations in serum and tissue (r2 = 0.83; P < 0.0001). High mucosal rather than serum VDZ levels correlated with a reduced endoscopic (P = 0.06) grade of mucosal inflammation. Furthermore, patients with a positive biochemical and endoscopic outcome had higher tissue levels of VDZ than patients without biochemical and endoscopic response (P < 0.01 and P = 0.04, respectively). Conclusions Tissue levels of VDZ may provide a better marker than serum levels for mucosal inflammation and objective treatment outcome at week 16. The potential of VDZ tissue levels for therapeutic drug monitoring in inflammatory bowel disease warrants further exploration.

scholarly journals An Evaluation of the Correlation between Hepcidin Serum Levels and Disease Activity in Inflammatory Bowel Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Zehra Betül Paköz ◽  
Cem Çekiç ◽  
Mahmut Arabul ◽  
Elif Sarıtaş Yüksel ◽  
Serkan İpek ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Active Phase ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Inflammatory Bowel ◽  
The Mean

Aim. While there are many well-defined serological markers for inflammatory bowel disease (IBD), there is limited evidence that they positively affect clinical outcomes. This study aimed to evaluate the correlation between hepcidin serum levels and disease activity in IBD.Materials and Methods. Eighty-five consecutive IBD patients were enrolled in the study. Hepcidin serum levels were assessed using an enzyme-linked immunosorbent assay (ELISA) and were compared with disease activity as well as the interleukin-6 (IL-6) and C-reactive protein (CRP) levels.Results. The mean hepcidin serum levels in Crohn’s disease (CD) patients in remission and in the active phase were3837±1436and3752±1274 pg/mL, respectivelyP=0.613. The mean hepcidin serum levels in ulcerative colitis (UC) patients in remission and in the active phase were4285±8623and3727±1176 pg/mL, respectivelyP=0.241. Correlation analysis between inflammatory markers and hepcidin serum levels indicated that there was no correlation between hepcidin levels and IL-6P=0.582or CRPP=0.783.Conclusion. As an acute-phase protein, hepcidin seems to have a lower efficacy than other parameters in the detection of activation in IBD.

Monitoring of serum levels of infliximab and anti-infliximab antibodies and its role in optimizing therapy of inflammatory bowel disease in children

2021 ◽  
Vol 16 (2) ◽  
pp. 14-21
Author(s):  
A.S. Illarionov ◽  
◽  
S.V. Petrichuk ◽  
A.P. Fisenko ◽  
T.V. Radygina ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Treatment Efficacy ◽  
Clinical Remission ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Residual Level ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Objective. To evaluate the prognostic value of serum levels of infliximab (IFX) and anti-IFX antibodies for predicting treatment efficacy in children with inflammatory bowel disease (IBD). Patients and methods. This study included 123 children with IBD (65 patients with ulcerative colitis (UC) and 58 patients with Crohn's disease (CD)) aged between 3 and 18 years. Children were examined upon the completion of an induction course of therapy and then after 1 year of therapy and between 1 and 3 years of treatment. The induction course was administered according to the scheme of 0–2–6 weeks; maintenance therapy was administered with 6-week and 8-week intervals. The residual level of IFX and the level of anti-IFX antibodies in serum were measured using enzyme-linked immunosorbent assay. Results. We observed a significant increase in the IFX level during clinical remission of CD (remission – 5.21 [3.32; 7.43] μg/mL; exacerbation – 2.42 [0.42; 4.51] μg/mL, p = 0.001) and UC (remission – 4.57 [3.4; 6.74] μg/mL; exacerbation – 0.63 [0.4; 3.27] μg/mL, p = 0.000). ROC analysis demonstrated high accuracy of our model based on measuring residual IFX level for distinguishing between exacerbation and remission in both CD patients (AUC = 0.812) and UC patients (AUC = 0.851). The optimal minimum level of IFX for maintaining clinical remission was 3.7 μg/mL in children with CD and 3.4 μg/mL in children with UC. Anti-IFX antibodies were detected in 18% of patients; children with exacerbation were 4.7 times more likely to have detectable level of anti-IFX antibodies than those in clinical remission. Conclusion. Monitoring of serum levels of IFX and anti-IFX antibodies is a promising method for predicting treatment efficacy and its optimization in children with IBD. Key words: inflammatory bowel disease, tumor necrosis factor-α, infliximab, residual level of infliximab, anti-infliximab antibodies

P329 Comparative Assessment of Adalimumab Trough Levels between Point-of-Care Testing and current Standard of Care (enzyme linked immunosorbent assay) in patients with Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S353-S353
Author(s):  
I Marsilio ◽  
D Maniero ◽  
G Lorenzon ◽  
A Rigo ◽  
R Cardin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Whole Blood ◽  
Point Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Point Of Care Testing ◽  
Deming Regression ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background Adalimumab (ADL) is a therapeutic monoclonal antibody that targets the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) and has been shown to effectively induce and maintain disease remission in patients with Inflammatory Bowel Disease (IBD). However, some patients fail to respond to this treatment, experiencing primary failure (no response to induction therapy), while others initially respond but lose efficacy over time (secondary failure). Therapeutic Drug Monitoring (TDM), in clinical practice, may lead to maintain therapeutic drug concentration thereby optimizing individual dosage regimen and improving treatment response. Recently, a point of care testing (POCT) has been developed to rapidly measure trough levels in patients taking ADL. Comparative data with current gold standard are lacking. Aim To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) ADL assay which analyze capillary whole blood and the comparative enzyme linked immunosorbent assays (ELISA) from serum samples. Methods From December 2020 to February 2021, consecutive patients (aged ≥ 18 years) taking ADA (Humira, Amgevita, Imraldi) were recruited at Gastroenterology Unit, Padua University Hospital, during outpatient visits. In each patient, ADL levels from capillary whole blood collected by finger stick were performed using the ProciseDx ADL assay with reportable range between 1.3 µg/mL - 51.5 µg/mL; at the same time, a serum sample from venous blood was collected to carry out Grifols’ Promonitor ELISA test (range ≤ 0.024 – 12 µg/mL). A Deming regression test was used to identify the correlation between the two methods. Results Sixty patients were enrolled (67% males with mean age of 3±14), with 80% of them having CD, 17% UC and 3% an undetermined-Inflammatory Bowel Disease (IBD-U). The assessment with ProciseDx POCT was feasible and required a turnaround time of 3±0.2 minutes while serum ELISA analysis required the collection of at least 40 samples (around three weeks at our centre) and 3 hours to be performed. Thirty patients (63% males with mean age of 41±14) had therapeutic levels as assessed by ProciseDx ADL assay lower than 1.3 or greater than 12 µg/mL, in accordance with ELISA assessment. Among the remaining 30 patients (70% males with mean age of 43±15), the correlation between the two tests was high (r of 0.858 (95% CI 0.720 – 0.930)). Conclusion The ProciseDx POCT has similar accuracy but was more rapid and easy to be performed in providing the results of TDM in outpatients taking ADL. This could lead to a more rapid and effective optimization of the biological drug, thus avoiding treatment failure.

scholarly journals SERUM INFLIXIMAB MEASUREMENT IN INFLAMMATORY BOWEL DISEASE PATIENTS IN REMISSION: A COMPARATIVE ANALYSIS OF TWO DIFFERENT METHODS IN A MULTICENTRIC BRAZILIAN COHORT

2018 ◽  
Vol 55 (2) ◽  
pp. 192-197 ◽  
Author(s):  
Fábio Vieira TEIXEIRA ◽  
Ligia Yukie SASSAKI ◽  
Rogerio SAAD-HOSSNE ◽  
Julio Pinheiro BAIMA ◽  
Daniéla Oliveira MAGRO ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Sensitivity And Specificity ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Rapid Test ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Elisa Assay ◽  
Inflammatory Bowel

ABSTRACT BACKGROUND: Infliximab (IFX) therapeutic drug monitoring is an important tool to guide therapeutic decision in inflammatory bowel disease patients. Currently, there are two methods to measure trough levels of IFX, ELISA assays or rapid tests. Despite that the ELISA assay is the most used method in therapeutic drug monitoring, the results take long to be available for clinical use, and it needs to be performed by trained personnel. In contrary, the results of a rapid test take 20 to 30 minutes to be available and can be performed by non-trained lab personnel. OBJECTIVE: The aim of the study was to compare a rapid test (QB-IFX) for quantitative determination of IFX level to one ELISA assay in a cohort of inflammatory bowel disease patients. METHODS: Cross-sectional multicentric study with 49 inflammatory bowel disease patients on maintenance therapy with IFX. Blood samples for IFX serum levels were collected immediately before infusion. IFX serum levels were classified as undetectable, low (<3.0 μg/mL), adequate (3.1-7.0 μg/mL) or high (>7.1 μg/mL). A sensitivity and specificity of each test and a comparison between tests was based on ROC curves. RESULTS: Thirty-four Crohn’s disease patients and 15 ulcerative colitis patients in clinical remission were evaluated. The majority of patients had low or adequate serum levels of IFX. In relation to the serum levels proportions with the two methods, there was no significant difference (P=0.84). The ROC analysis identified a concentration threshold >2.9 μg/mL with the QB-IFX test (area under the ROC, 0.82; P<0.0001, sensitivity, 100%; specificity, 61.9%), and >3.83 μg/mL using the ELISA assay (area under the ROC, 0.96; P<0.0001, sensitivity, 100%; specificity, 92.9%). CONCLUSION: QB-IFX and ELISA assays to measure IFX levels were comparable. Both methods had accurate sensitivity and specificity to detect undetectable, low and adequate levels, but had showed low specificity for supra therapeutic levels of IFX.

P092 COMPARISON OF INFLIXIMAB AND ADALIMUMAB CONCENTRATIONS BETWEEN THE ENZYME-LINKED IMMUNOSORBENT ASSAY AND THE HOMOGENEOUS MOBILITY SHIFT ASSAY (HMSA) IN INFLAMMATORY BOWEL DISEASE: AN UPDATE FOLLOWING IMPLEMENTATION OF CORRECTIVE MEASURES FOR THE HMSA

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S69-S69
Author(s):  
Konstantinos Papamichail ◽  
William Clarke ◽  
Niels VandeCasteele ◽  
Katharine Germansky ◽  
Joseph Feuerstein ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immunosorbent Assay ◽  
Drug Concentration ◽  
Bowel Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Mobility Shift ◽  
Drug Concentrations ◽  
Inflammatory Bowel ◽  
Mobility Shift Assay

Abstract Background and aims We previously showed a discrepancy between a commercially available enzyme-linked immunosorbent assay (ELISA) and the homogenous mobility shift assay (HMSA) for both infliximab and adalimumab concentrations in patients with inflammatory bowel disease (IBD).1 Based also on the results of this study, Prometheus Laboratories initiated a comprehensive review of their HMSA assays and found that there was an upward drift for both infliximab and adalimumab over a 2-year period, including when our study was being performed. Prometheus corrected the errant values and reported the revised drug concentrations to physicians. We aimed to compare these two assays following the implementation of these corrective measures. Methods Samples from patients with IBD either on infliximab or adalimumab maintenance therapy were prospectively evaluated using both ELISA (InformTx™, Inform Diagnostics) (for research purposes) and the HMSA (ANSER™, Prometheus Laboratories) (performed clinically). Comparison of drug concentrations between assays was performed as previously described.1 Results In total 74 samples were analysed (infliximab, n=45; adalimumab, n=29). Drug concentrations (median [interquartile range, IQR]) were still significantly higher when measured by the HMSA compared to ELISA for foth infliximab (9 [7.1–12.4] vs. 5.7 [4.8–9] μg/ml; p&lt;0.001, respectively) and adalimumab (12.9 [10.3–16.9] vs. 10.6 [8.6–14] μg/ml; p=0.036, respectively). The correlation of infliximab and adalimumab concentrations between assays is depicted in Figure 1. Agreement between assays was moderate [ICC: 0.658; 95% confidence interval (CI): -0.080 to 0.892; p&lt;0.001] for infliximab and strong (ICC = 0.826, 95%CI: -0.066 to 0.949, p&lt;0.001) for adalimumab. A Bland–Altman plot of infliximab and adalimumab concentrations to compare the two assays is shown in Figure 2. Qualitative agreement in drug concentration status (therapeutic or sub-therapeutic) was only minimal between assays using &gt;5 μg/ml (K = 0.299, p=0.005), &gt;7 μg/ml (K = 0.303, p=0.005) or &gt;10 μg/ml (K = 0.323, p=0.003) as therapeutic drug concentrations for infliximab, while for adalimumab was weak using &gt;10 μg/ml as therapeutic drug concentrations (K = 0.437, p=0.004), although overall agreement using either &gt;5 or &gt;7 μg/ml as therapeutic drug concentrations was 97%. Conclusions These data suggest that although the correlation between the ELISA and the HMSA was very good for both infliximab and adalimumab it is difficult to compare absolute drug concentrations. Until commercial assays are properly cross-validated and standardized, assay-dependent drug concentration thresholds may need to be applied to better interpret therapeutic drug monitoring results and it is advisable that patients are monitored with the same assay. 1Inflamm Bowel Dis. 2019 Sep 27. https://doi.org/10.1093/ibd/izz202. [Epub ahead of print]

scholarly journals Serum Interleukin (IL)-23 and IL-17 Profile in Inflammatory Bowel Disease (IBD) Patients Could Differentiate between Severe and Non-Severe Disease

2021 ◽  
Vol 11 (11) ◽  
pp. 1130
Author(s):  
Laura A. Lucaciu ◽  
Maria Ilieș ◽  
Ștefan C. Vesa ◽  
Radu Seicean ◽  
Shahida Din ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Decision Making ◽  
Severe Disease ◽  
Clinical Decision ◽  
Serum Levels ◽  
Fecal Calprotectin ◽  
Mucosal Inflammation ◽  
Diagnostic Role ◽  
Inflammatory Bowel

Interleukin (IL)-17 and IL-23 are crucial for mediating gut mucosal inflammation in inflammatory bowel disease (IBD), which has led to new therapeutic strategies. We assessed the relevancy of IL-17 and IL-23 serum levels as potential biomarkers towards severe IBD discrimination and disease-related complications. Sixty-two patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) were included. Serum IL-17 and IL-23 were measured by sandwich enzyme-linked immunosorbent assays (ELISA). IL-23 and fecal calprotectin (FCal) were significantly higher in severe CD (p < 0.001) and UC (p < 0.001 and p = 0.001, respectively), compared to mild or moderate. Elevated C-reactive protein (CRP) was correlated with severe disease only in CD (p = 0.008), whereas for UC, disease severity was associated with increased IL-17 values (p < 0.001). Diagnostic role of IL-23 was superior to FCal in discriminating between severe and mild to moderate CD (p < 0.001). IL-23 levels were also significantly higher in CD patients with intestinal complications (p = 0.04). Both IL-17 and IL-23 correlate with IBD severity, and IL-23 might be a promising novel biomarker for severe CD. Identifying the dominant IL pathway involved in IBD severity could serve as guidance for clinical decision-making on biologic therapy.

Therapeutic drug monitoring with vedolizumab in inflammatory bowel disease

2020 ◽  
Vol 65 (4) ◽  
Author(s):  
Daniela Pugliese ◽  
Giuseppe Privitera ◽  
Fabrizio Pizzolante ◽  
Antonio Gasbarrini ◽  
Luisa Guidi ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Inflammatory Bowel

scholarly journals Tu1789 – Treatment Response to Ustekinumab and Vedolizumab in Inflammatory Bowel Disease: the Predictive Role of Gut Microbiota

2019 ◽  
Vol 156 (6) ◽  
pp. S-1124
Author(s):  
Clara Caenepeel ◽  
Sara Vieira-Silva ◽  
Jorge F. Vázquez-Castellanos ◽  
Bram Verstockt ◽  
Marc Ferrante ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Bowel Disease ◽  
Predictive Role ◽  
Inflammatory Bowel

scholarly journals A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 162-163
Author(s):  
M Mikail ◽  
A Wilson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pyoderma Gangrenosum ◽  
Bowel Disease ◽  
Complete Resolution ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Median Serum ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

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