scholarly journals P405 Development and validation of a rapid immunoassay for monitoring of ustekinumab concentrations in Inflammatory Bowel Disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S412-S412
Author(s):  
D Thomas ◽  
G Compernolle ◽  
J P Guedelha Sabino ◽  
M Ferrante ◽  
S Vermeire ◽  
...  
Keyword(s):  
Serum Sample ◽  
Clinical Decision Making ◽  
Point Of Care ◽  
Fiber Surface ◽  
Clinical Decision ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Several studies have reported an association between ustekinumab serum concentrations and clinical outcomes, suggesting a potential role of therapeutic drug monitoring (TDM) for guiding clinical decision-making and treatment optimisation in ustekinumab-treated patients with inflammatory bowel diseases. Usually, ustekinumab concentrations are measured with an enzyme-linked immunosorbent assay (ELISA). Disadvantages of using ELISA for TDM are the rather long time-to-result and the necessity of collecting multiple samples in order to reduce the price per determination. The performance of TDM could be further enhanced by using a rapid point-of-care assay, which would allow immediate and individualised dose optimisation based on real-time pharmacokinetic information instead of awaiting dose adjustments at the subsequent administration. Methods A fiber-optic surface plasmon resonance (FO-SPR) assay was developed on a White FOx 1.0 device (FOx Biosystems), using a monoclonal antibody (MA)/MA sandwich approach. MA-UST56A2D11 was covalently immobilised to a gold-sputtered fiber surface to capture ustekinumab. After incubation with the serum sample, biotinylated MA-UST56C1H12 was used for detection of bound ustekinumab, and the signal was amplified using a polyclonal anti-biotin antibody conjugated to gold nanoparticles. A calibration curve was constructed by spiking ustekinumab in 1/1000 diluted human serum. Recovery and imprecision were assessed, and the performance of the FO-SPR assay was compared with that of our previously developed in-house ELISA using twelve serum samples of ustekinumab-treated patients. Results A dose-response curve ranging from 1.25 – 40 ng/mL was obtained, allowing quantification of ustekinumab concentrations from 0.31 µg/mL (using a 1/250 dilution) up to 80 µg/mL (using a 1/2000 dilution) in serum samples. Measurement of ustekinumab-spiked samples (1 – 25 µg/mL) showed an average intra-assay recovery of 111% (range: 95-124%) and imprecision of 10% (range: 8-15%), and an average inter-assay recovery of 109% (range: 100-122%) and imprecision of 5% (range: 1-8%). Comparison of measurements between FO-SPR and ELISA revealed a very good correlation (Pearson r coefficient of 0.980, 95% CI 0.928-0.995, p<0.001; Figure 1). Using a pre-functionalised fiber, the FO-SPR assay requires 55 min for measuring a single ustekinumab serum sample. Conclusion A rapid FO-SPR assay for quantification of ustekinumab concentrations in serum samples was established and showed a very good correlation with ELISA. The reduced assay time and the possibility of measuring a single sample are advantages compared to ELISA, and may allow implementation of FO-SPR as a point-of-care diagnostic tool.

scholarly journals Rapid point-of-care anti-infliximab antibodies detection in clinical practice: comparison with ELISA and potential for improving therapeutic drug monitoring in IBD patients

2021 ◽  
Vol 14 ◽  
pp. 175628482199990
Author(s):  
Sonia Facchin ◽  
Andrea Buda ◽  
Romilda Cardin ◽  
Nada Agbariah ◽  
Fabiana Zingone ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Point Of Care ◽  
Drug Clearance ◽  
Elisa Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Inflammatory Bowel

Anti-drug antibodies can interfere with the activity of anti-tumor necrosis factor (TNF) agents by increasing drug clearance via direct neutralization. The presence of anti-drug antibodies is clinically relevant when trough drug concentrations are undetectable or sub-therapeutic. However, traditional immunoassay is not easily and rapidly accessible, making the translation of the results into treatment adjustment difficult. The availability of a point-of-care (POC) test for therapeutic drug monitoring (TDM) might represent an important step forward for improving the management of inflammatory bowel disease (IBD) patients in clinical practice. In this pilot study, we compared the results obtained with POC tests with those obtained by enzyme-linked immunosorbent assay (ELISA) in a group of IBD patients treated with Infliximab (IFX). We showed that POC test can reliably detect presence of antibody-to-IFX with 100% of specificity and 76% sensitivity, in strong agreement with the ELISA test ( k-coefficient = 0.84).

scholarly journals Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin

2018 ◽  
Vol 11 ◽  
pp. 1756283X1774473 ◽  
Author(s):  
Yannick Derwa ◽  
Christopher J.M. Williams ◽  
Ruchit Sood ◽  
Saqib Mumtaz ◽  
M. Hassan Bholah ◽  
...  
Keyword(s):  
Decision Making ◽  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Medical Therapy ◽  
Bowel Disease ◽  
Clinical Decision Making ◽  
Point Of Care ◽  
Clinical Decision ◽  
Mucosal Inflammation ◽  
Inflammatory Bowel

Objectives: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. Methods: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare and faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. Results: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84–17.0] and UC (OR 10.8; 95% CI 1.8–64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49–5.39; and OR 0.21; 95% CI 0.21–1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84–34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46–6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47–43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28–14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. Conclusions: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.

scholarly journals Precision medicine in inflammatory bowel disease: concept, progress and challenges

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 54 ◽  
Author(s):  
Simon P. Borg-Bartolo ◽  
Ray Kiran Boyapati ◽  
Jack Satsangi ◽  
Rahul Kalla
Keyword(s):  
Precision Medicine ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Underlying Disease ◽  
Response To Therapy ◽  
Current Evidence ◽  
Disease Biology ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Individual

Crohn’s disease and ulcerative colitis are increasingly prevalent, relapsing and remitting inflammatory bowel diseases (IBDs) with variable disease courses and complications. Their aetiology remains unclear but current evidence shows an increasingly complex pathophysiology broadly centring on the genome, exposome, microbiome and immunome. Our increased understanding of disease pathogenesis is providing an ever-expanding arsenal of therapeutic options, but these can be expensive and patients can lose response or never respond to certain therapies. Therefore, there is now a growing need to personalise therapies on the basis of the underlying disease biology and a desire to shift our approach from “reactive” management driven by disease complications to “proactive” care with an aim to prevent disease sequelae. Precision medicine is the tailoring of medical treatment to the individual patient, encompassing a multitude of data-driven (and multi-omic) approaches to foster accurate clinical decision-making. In IBD, precision medicine would have significant benefits, enabling timely therapy that is both effective and appropriate for the individual. In this review, we summarise some of the key areas of progress towards precision medicine, including predicting disease susceptibility and its course, personalising therapies in IBD and monitoring response to therapy. We also highlight some of the challenges to be overcome in order to deliver this approach.

scholarly journals Serum Adalimumab Levels After Induction Are Associated With Long-Term Remission in Children With Inflammatory Bowel Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Marianna Lucafò ◽  
Debora Curci ◽  
Matteo Bramuzzo ◽  
Patrizia Alvisi ◽  
Stefano Martelossi ◽  
...  
Keyword(s):  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Level Measurement ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Term Response

Introduction: Adalimumab is effective in inducing and maintaining remission in children with inflammatory bowel diseases (IBD). Therapeutic drug monitoring is an important strategy to maximize the response rates, but data on the association of serum adalimumab levels are lacking. This study aimed to assess the association of adalimumab concentrations at the end of induction and early during maintenance for long-term response.Materials and Methods: Serum samples for adalimumab level measurement were collected during routine visits between adalimumab administrations and therefore not necessarily at trough, both during the induction (week 4 ± 4) and maintenance phases (week 22 ± 4, 52 ± 4, and 82 ± 4). Adalimumab and anti-adalimumab antibodies were measured retrospectively using enzyme-linked immunosorbent assays (ELISA). Disease activity was determined by Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index.Results: Thirty-two children (median age 14.9 years) were enrolled. Sixteen, 15, 14, and 12 patients were in remission at weeks 4, 22, 52, and 82, respectively. Median adalimumab concentration was higher at all time points in patients achieving sustained clinical remission. Adalimumab levels correlated with clinical and biochemical variables. Adalimumab concentration above 13.85 and 7.54 μg/ml at weeks 4 and 22 was associated with remission at weeks 52 and 82.Conclusions: Adalimumab non-trough levels are associated with long-term response in pediatric patients with IBD.

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.

Novel immunoassays for detection of CUZD1 autoantibodies in serum of patients with inflammatory bowel diseases

2017 ◽  
Vol 55 (10) ◽  
Author(s):  
Sofia Farkona ◽  
Antoninus Soosaipillai ◽  
Panagiota Filippou ◽  
Christos Liaskos ◽  
Dimitrios P. Bogdanos ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Solid Phase ◽  
Disease Onset ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Phenotype ◽  
Serum Samples ◽  
Multicenter Studies ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Disease Location

AbstractBackground:Pancreatic autoantibodies (PABs) are detected in patients with inflammatory bowel disease (IBD). Their prevalence is higher in Crohn’s disease (CrD) than in ulcerative colitis (UC). Glycoprotein 2 (GP2) and, more recently, CUB and zona pellucida-like domain-containing protein 1 (CUZD1) have been identified as target autoantigens of PAB. The clinical utility of CUZD1 autoantibodies has only recently been assessed by indirect immunofluorescence (IIF) assays. In this study, we developed and validated novel immunoassays for the detection of CUZD1 autoantibodies.Methods:Recombinant CUZD1 protein was utilized as a solid-phase antigen for the development of two immunoassays for the detection of IgG and IgA CUZD1 autoantibodies. Serum samples from 100 patients with CrD, 100 patients with UC, 129 patients assessed for various autoimmune diseases (vADs) and 50 control individuals were analyzed.Results:Two immunofluorometric assays for the detection of IgG and IgA CUZD1-specific antibodies were developed. CUZD1 autoantibodies were detected in 12.5% (25/200) IBD patients, including 16% of patients with CrD and in 9% of patients with UC (CrD vs. UC, p<0.05), compared with 3.1% (4/129) patients suspected of having vADs (CrD vs. ADs, p<0.05; UC vs. ADs, p=0.08). CUZD1 autoantibody positivity was not found to be related to disease location, age of disease onset or disease phenotype.Conclusions:This is the first study to describe novel IgA and IgG CUZD1 autoantibody enzyme-linked immunosorbent assay. These immunoassays agree well with standard IIF techniques and can be utilized in multicenter studies to investigate the diagnostic and clinical utility of CUZD1 autoantibodies.

scholarly journals Conflicts of Interest in Inflammatory Bowel Disease Articles on UpToDate

2019 ◽  
Author(s):  
Rishad Khan ◽  
Juana Li ◽  
Michael A Scaffidi ◽  
Nikko Gimpaya ◽  
Bianca Pivetta ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Decision Making ◽  
Conflicts Of Interest ◽  
Point Of Care ◽  
Clinical Decision ◽  
Cross Sectional ◽  
Inflammatory Bowel ◽  
Sectional Analysis ◽  
Open Payments

Abstract Background Financial conflicts of interest (FCOIs) are widespread in inflammatory bowel disease (IBD) and may be particularly important in point-of-care (POC) resources, such as UpToDate, that are used to aid clinical decision making. In this study, we determined the prevalence of industry payments from companies making biologic medications for IBD to contributors of UpToDate articles on IBD. Methods This cross-sectional analysis included UpToDate articles that mention the use of biologic medications for IBD. We collected the names of the contributors (authors and editors) and their disclosures on UpToDate. We then searched for their names on the Center for Medicare and Medicaid Open Payments database and compared the payment information from 2013 to 2018 with UpToDate's disclosures. We presented data per episode, which describes one instance of participation by one person in one article, regardless of whether that person contributed to multiple articles. Results We identified 23 articles on the treatment of Crohn's disease and ulcerative colitis that mentioned the use of biologic medications, with 86 total episodes. Sixty-two (72%) episodes involved FCOIs. The median payment associated with each episode was $$55 (interquartile range = $44 to $145,241). Contributors did not fully disclose FCOIs in 41 (48%) episodes. Deputy editors, who are required to be free of FCOIs, in general did not have substantial episodes involving FCOI. Conclusions We found that UpToDate articles on inflammatory bowel disease involve substantial FCOI, many of which are not disclosed. The presence of these FCOIs may hamper trust in the objectivity of treatment recommendations.

scholarly journals SMALL-BOWEL CAPSULE ENDOSCOPY IN INFLAMMATORY BOWEL DISEASE TYPE UNCLASSIFIED

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Ana-Maria Singeap ◽  
Irina Girleanu ◽  
Stefan Chiriac ◽  
Tudor Cuciureanu ◽  
Carol Stanciu ◽  
...  
Keyword(s):  
Small Bowel ◽  
Diagnostic Criteria ◽  
Capsule Endoscopy ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Crohn’S Colitis ◽  
Crohn's Colitis ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background and aim Ulcerative colitis (UC) and Crohn’s disease (CD) are idiopathic inflammatory bowel diseases (IBD) with no unique, gold standard diagnostic test. UC and Crohn’s colitis are in approximately 10% of cases impossible to be distinguished. The term IBD type unclassified (IBD-U) is officially proposed for the cases of chronic colitis showing overlapping endoscopic, radiological, and biopsy histological features between UC and CD, while indetermined colitis is reserved for colectomy specimen. Our aim was to evaluate the role of small-bowel capsule endoscopy (SBCE) in the diagnostic work-up of IBD-U. Material and methods We prospectively studied all cases of IBD-U explored by SBCE in our tertiary referral gastroenterology center. Patients were investigated by SBCE after contraindications were excluded. Diagnostic criteria for small bowel CD consisted in more than 3 ulcerations, irregular ulcers or stenosis; if fulfilled, Crohn’s colitis was sustained. The absence of CD features in the small bowel (SB) strengthened the assumption of UC. Follow-up data were recorded. Results Fifteen patients with IBD-U were explored by SBCE. Seven patients had SB lesions meeting the diagnostic criteria for CD. The remaining eight examinations showed no SB significant findings; therefore, they were classified as UC. No complications occurred. The patients were treated accordingly. Follow-up data recorded a case of colectomy for refractory UC. Conclusions SBCE is a useful safe tool in the management of IBD unclassified. Due to its diagnostic valences, SBCE plays a particular role in the process of proper clinical decision-making.

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