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Bland–Altman’s plot. The difference in ADL concentrations vs. the average (µg/mL) between Promonitor and QB. The dashed blue line represents the bias and dashed orange lines represent the 95% limit of agreement.
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The introduction of point-of-care (POC) assays into clinical practice in patients with inflammatory disease enables on-demand therapeutic decision making. The aim of this study was to compare the POC test Quantum blue (Bühlmann Laboratories) for infliximab (IFX), adalimumab (ADL), and its anti-drug antibodies with the traditional ELISA assay (Promo...
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Introduction: Therapeutic drug monitoring (TDM) has proven to be a valuable strategy for optimizing biologic therapies, among which are anti-tumor necrosis factor (anti-TNF) treatments in inflammatory bowel disease (IBD). In particular, reactive TDM has been shown to manage treatment failures more cost-effectively than empirical dose adjustments fo...
Citations
... Our findings indicate that serum levels were higher when measured using the Quantum Blue assay than those assessed by the Promonitor assay, consistent with Cherry et al.'s, 39 who report higher adalimumab levels measured by rapid tests than with ELISA assays. Toja-Camba et al., 40 which employed the same comparison methods as ours, reported no significant differences between the assays for adalimumab, which contrasts with our findings. While the Spearman correlation observed in their study for both drugs indicated a strong correlation between the two assays, our results demonstrated a moderate correlation. ...
Crohn’s disease (CD) involves immune system interactions with intestinal tissue, driven by pro-inflammatory cytokines like Tumor Necrosis Factor (TNF-α). Adalimumab, targeting TNF-α, regulates associated inflammatory responses. Despite being humanized, it may induce immunogenic processes, affecting treatment effectiveness. Thus, monitoring serum adalimumab and anti-drug antibody (ADA) levels can optimize therapy. Understanding genetic factors influencing adalimumab response can enhance personalized treatment and improve patient quality of life. We aimed to quantify adalimumab serum levels, assess test interchangeability, detect ADA, examine immune complex formation, and investigate genetic phenotypes related to immunogenicity in CD patients. Seventy CD patients in the maintenance phase with adalimumab were classified into active (CDA) and remission (CDR) groups. Adalimumab concentration was determined via enzyme-linked immunosorbent assay (ELISA—Promonitor) and lateral flow assay (Quantum Blue), with assay interchangeability assessed statistically. ADA and immune complex formation were quantified using ELISA assays. DNA was genotyped for the genes ATG16L1, CD96, and CD155. No significant differences in adalimumab serum concentrations were observed between groups, regardless of the assay. However, a statistical difference between the tests indicated measurement disparity (P = 0.003), with moderate agreement (Lin’s correlation of 0.247). ADA was detected in 4 of 27 of the patients with infratherapeutic levels, 3 in the CDA group and 1 in the CDR group. Analysis of immune complexes revealed significantly higher concentrations in the CDA group (P = 0.0125). The genotypic evaluation revealed significant associations for the CD96 CC (wild-type) genotype with higher CRP levels, colonic involvement, and infratherapeutic levels of adalimumab. ATG16L1 CC genotype was associated with higher CDEIS and fecal calprotectin values, while the variant (TT) genotype had lower platelet counts. The effectiveness of treatment with adalimumab was not directly related to higher medication levels in this cohort. The disparity between tests indicates the need to use only one test in patient follow-up to ensure accuracy in therapeutic monitoring. Genotypic differences highlight the correlation between the wild genotype for CD96 and ATG16L1 with unfavorable laboratory and endoscopic response to adalimumab. Finally, the more significant levels of immune complexes in the CDA group indicate an association with a worse response to adalimumab.
... This was more pronounced in the high-range subgroup, where the mean difference was 2.23 µg/mL. Toja-Camba et al. 17 also observed that QB slightly overestimated the infliximab concentration, with a median C-trough of 4.86 µg/mL for ELISA (Promonitor) and 6.15 µg/mL for QB (p < 0.001). Two older studies, on the other hand, observed systematic differences in the opposite direction, with ELISA-based measurements (both Sanquin) 2.62 and 0.92 µg/mL higher than QB, respectively. ...
... We distinguished two categories of C-trough results (<5 vs. ≥5 mg/L), whereas other groups used three different categories (<3, 3-7 and >7 mg/L). 17,[19][20][21][22] The κ statistics in these studies ranged from 0.67 to 0.81, corresponding with substantial to almost perfect agreement. Our κ of 0.62 was slightly lower, but an infliximab concentration ≥5 mg/L is internationally accepted as the recommended target C-trough for children in the maintenance phase. ...
Objectives
Infliximab is an antitumour necrosis factor agent used to treat inflammatory bowel disease (IBD). Measurement of infliximab trough concentrations (C‐troughs) are used to optimize drug exposure and improve outcomes. Currently, enzyme‐linked immunosorbent assays (ELISAs) are used predominantly for this purpose. Novel lateral flow immunoassays provide a rapid result.
Methods
We collected 100 paired serum samples of adolescents and young adults with IBD, who were treated with infliximab maintenance infusions. C‐troughs were measured with the Quantum Blue® lateral flow test (QB) with ELISA. Results were categorized as low‐range (mean C‐trough ≤5 µg/mL) or high‐range (>5 µg/mL). A Bland–Altman plot was created with limits of clinical acceptability set at ≤2 µg/mL for low‐range and ≤40% for high‐range C‐troughs. A concordance matrix was created to evaluate the C‐trough‐based clinical scenario (whether or not to escalate infliximab) using a cutoff value of 5 µg/mL.
Results
Agreement between QB and ELISA was good (intraclass correlation coefficient: 0.85). In the low‐range, 90% (95% confidence interval [CI]: 79–96) of measurements were within the limits of clinical acceptability. In the high‐range this was 67% (95% CI: 53–79). QB provided higher results than ELISA. The concordance matrix showed 81% agreement (95% CI: 72–88, κ : 0.62).
Conclusions
Lateral flow‐ and ELISA‐based infliximab C‐trough measurements were in agreement. The swift establishment of infliximab C‐troughs matters for patients experiencing increased disease activity. In the event of a low C‐trough, prompt dose escalation can be initiated.
... Despite some reported acceptable agreement between ELISAs and POC tests, not all tests exhibit the same recovery of international standards, affecting result comparability and uniform target concentrations. [149][150][151] Adequate training of nonlaboratory personnel is crucial for using these devices. 152 Furthermore, implementing international standards and universal calibrators, along with participation in proficiency testing rounds, is essential for continuous accuracy and precision of POC testing. ...
Background
Infliximab, an anti–tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research.
Methods
The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement.
Results
Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record–integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration.
Conclusions
Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory.
Background
New point-of-care (POC) techniques offer rapid results and address some of the limitations of traditional enzyme-linked immunosorbent assay (ELISA) methods, such as lengthy processing times and delays in therapeutic decision making. It is crucial to evaluate the comparability of POC assays with established ELISA methods to ensure accuracy and reliability in therapeutic drug monitoring. This study aimed to evaluate the analytical performance and clinical utility of the AFIAS-10 POC assay compared with the Promonitor ELISA for quantifying serum concentrations of infliximab (IFX) and adalimumab (ADA) and detecting antidrug antibodies (ATIs and ATAs).
Methods
A prospective study was conducted from October 2023 to April 2024, including 225 samples from patients with immune-mediated diseases. The samples were analyzed using both AFIAS-10 POC and Promonitor ELISA assays. To assess the agreement between the 2 methods in terms of quantification, Bland–Altman analysis was performed by examining the mean difference and establishing limits of agreement.
Results
The Pearson correlation coefficient indicated strong correlations for IFX (r = 0.932) and ADA (r = 0.967) between the 2 assays. The mean difference between POC and ELISA for IFX was −0.78 mcg/mL and for ADA was 1.54 mcg/mL, respectively. The POC assay tended to underestimate IFX concentrations and overestimate ADA concentrations compared with ELISA.
Conclusions
The AFIAS-10 POC assay demonstrated good correlation and concordance with the ELISA method for the quantification of IFX and ADA, as well as for detecting anti-IFX and anti-ADA antibodies. However, this correlation was notably lower at higher drug concentrations.
Purpose
Adalimumab (ADA) is a systemic biological treatment option approved for the treatment of noninfectious uveitis (NIU); however, up to 40% of patients do not respond to the drug, either in a primary or secondary manner. Here, we evaluated the proteomic profile of patients with NIU who fail to ADA to identify proteins implicated in intraocular inflammation, as well as potential biomarkers for treatment response and novel therapeutic targets.
Methods
Cross-sectional observational study of patients with NIU under ADA treatment for six or more months. Tears were collected with microcapillary tubes and protein analyzed by data-independent acquisition/sequential window acquisition of all theoretical mass spectra. Differentially expressed proteins (DEPs) were defined based on the fold change between their expression in nonresponders (NR) and responders (R). Protein network and gene ontology analysis were performed. The χ² test for trend and receiver operating characteristic (ROC) curves were used to evaluate potential biomarkers of treatment response.
Results
Twenty-nine DEPs, 14 upregulated and 15 downregulated, were detected in NR. These proteins were mainly related to enhanced neutrophil effector functions and redox imbalance. ROC analysis identified defensin-1,3 (DEF-1,3), biotinidase, and ATP-binding cassette transporter A1 as potential biomarkers for treatment response.
Conclusions
This is the first study on a clinical cohort of patients with noninfectious uveitis that identifies tear proteins related to neutrophil hyperactivation as drivers of the persistent intraocular inflammation observed in NR to ADA and provides evidence that targeting interleukin 6, Janus kinases, or the complement cascade could be potential alternative therapeutic strategies in these patients. Our results indicate the potential of high-throughput proteomics to provide insights into the underlying pathological mechanisms of persistent intraocular inflammation observed in patients who do not adequately respond to anti-TNF treatment and the value of tear proteomics as a tool for personalized medicine.
Objectives:
To evaluate the analytical performance and clinical utility of the POC-AFIAS assay in comparison with two ELISA established assays for quantifying serum concentrations of ustekinumab.
Methods:
A prospective study was conducted. Consecutive serum samples from adult patients undergoing treatment with ustekinumab were collected. Three analytical techniques were compared for the quantification of ustekinumab serum concentrations: the AFIAS-10® POC assay (POC-AFIAS), the Promonitor® ELISA assay (ELISA-PRO), and the ELISA Ridascreen® assay (ELISA-RDSC). Ustekinumab concentrations were evaluated within three therapeutic ranges: <1μg/mL, 1-4.5μg/mL, and >4.5μg/mL. Statistical analysis included Pearson correlation, intra-class correlation coefficient, and Bland-Altman analysis.
Results:
A total of 104 patients were included in the study. The median ustekinumab concentrations measured were 5.22μg/mL (POC-AFIAS), 3.99μg/mL (ELISA-PRO), and 4.50μg/mL (ELISA-RDSC). Strong correlations were observed between techniques (POC-AFIAS and ELISA-PRO: r=0.921, POC-AFIAS and ELISA-RDSC: r=0.940, ELISA-PRO and ELISA-RDSC: r=0.976). The Bland-Altman analysis revealed a bias difference of 1.81μg/mL between POC-AFIAS and ELISA-PRO, and 1.27μg/mL between POC-AFIAS and ELISA-RDSC. Agreement rates varied by therapeutic range, with the highest agreement observed within the therapeutic range (97.3%) and lower agreement for supra-therapeutic concentrations (74.6%).
Conclusion:
This study demonstrated that the POC-AFIAS assay provides comparable results to established ELISA techniques for quantifying serum concentrations of ustekinumab, particularly within the therapeutic range. The findings suggest that the POC-AFIAS assay offers a rapid and effective tool for managing ustekinumab therapy in clinical practice.
