Infliximab and Adalimumab Concentrations May Vary Between the Enzyme-Linked Immunosorbent Assay and the Homogeneous Mobility Shift Assay in Patients With Inflammatory Bowel Disease: A Prospective Cross-Sectional Observational Study

Clarke, William T; Papamichael, Konstantinos; Casteele, Niels Vande; Germansky, Katharine A.; Feuerstein, Joseph D.; Melmed, Gil Y.; Siegel, Corey A.; Irving, Peter M; Cheifetz, Adam S.

doi:10.1093/ibd/izz202

Cited by 14 publications

(15 citation statements)

References 5 publications

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“…8 The difference in the numbers could be related to difference in IFX concentration detection assays used. 19,20 In addition to what was found in the PANTS study, we demonstrated that patients who had an infusion-4 level of ≥5 µg/mL had a 90% decrease of FCP from baseline to infusion 4 by, whereas patients with an IFX< 5 µg/mL had only a 35% decrease after induction.…”

Section: Discussionsupporting

confidence: 76%

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn’s Disease

Colman

Tsai

Jackson

et al. 2020

Inflammatory Bowel Diseases

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Background The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations. Methods We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn’s disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP <250 µg/g, with clinical response defined as a weighted Pediatric Crohn’s Disease Activity Index <12.5 or Δ>17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs). Results Among 56 CD patients, ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934, P < 0.001) and nCD64 <6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of >9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP <250 and FCP <100, respectively. We found patients achieving end of induction trough >5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels <5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031). Conclusions This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

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Section: Discussionsupporting

confidence: 76%

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn’s Disease

Colman

Tsai

Jackson

et al. 2020

Inflammatory Bowel Diseases

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“…We also found that infliximab and adalimumab concentrations before and after the correction of the HMSA were significantly different, both quantitatively and qualitatively. This is in line with previous studies showing discrepancies among assays used for evaluating biologic drug concentrations [8,9,14,15]. Moreover, we identified adalimumab concentration thresholds of 22.4 µg/mL before the corrected measures and 14.4 µg/mL after the corrected measures discriminated patients with or without treatment failure.…”

Section: Discussionsupporting

confidence: 91%

“…However, these thresholds can vary depending on the targeted clinical outcome, IBD phenotype, and TDM assay used [7]. Regarding the latter, we have previously shown a discrepancy between a commercially available enzyme-linked immunosorbent assay (ELISA) and a commercially available homogeneous mobility shift assay (HMSA), for both infliximab and adalimumab concentrations [8,9]. Based on these results, a comprehensive review of the HMSA assays was initiated and an upward drift for both infliximab (from December 2017 to May 2019) and adalimumab (from August 2017 to May 2019) was found, including the period during which our study was performed.…”

Section: Introductionmentioning

confidence: 99%

Clinical Impact of Corrections to Infliximab and Adalimumab Monitoring Results with the Homogeneous Mobility Shift Assay

Papamichael

Thomas

Banty

et al. 2020

JCM

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An upward drift for both infliximab and adalimumab concentrations measured by the homogenous mobility shift assay (HMSA) was previously reported. We aimed to investigate the impact of this drift on clinical care of patients with inflammatory bowel disease. This was a retrospective, multicenter study. Providers reviewed the individual patient data and drug concentrations before and after the laboratory corrections and then documented whether a different clinical decision would have been made had the corrected drug concentration been originally reported. A multivariable Cox proportional hazards regression analysis was performed to investigate the association of a documented treatment change with treatment failure, defined as drug discontinuation for primary nonresponse, loss of response, or serious adverse event, adjusting for confounding factors. The study population consisted of 479 patients (infliximab, n = 219; adalimumab, n = 260). Upon review, 14.9% (71/479) patients would have had a different treatment decision made had the corrected drug concentration been initially reported. After a median follow-up of 10.6 months, 25.7% of patients (123/479) had treatment failure. A theoretical different clinical decision based on the corrected drug concentrations was not associated with treatment failure (adjusted hazard ratio (HR): 1.452; 95% confidence interval (CI): 0.805–2.618; p = 0.216), which was consistent for both infliximab (adjusted HR: 1.977; 95% CI: 0.695–5.627; p = 0.201) and adalimumab (adjusted HR: 1.484; 95% CI: 0.721–3.054; p = 0.284). The drift in infliximab and adalimumab concentrations in the HMSA assay affected treatment decisions in 15% of cases. However, this discrepancy was not associated with a higher cumulative probability for treatment failure.

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“…Furthermore, although a comparison of commercially available homogenous mobility shift assay and ELISA to assess infliximab and adalimumab concentrations found good correlation between the assays for each biologic (infliximab: r = 0.861; P < 0.001; adalimumab: r = 0.935; P < 0.001), agreement between the assays was weak (infliximab intraclass correlation coefficient = 0.356 [95% CI, −0.069 to 0.720]; P < 0.001; adalimumab intraclass correlation coefficient = 0.395 [95% CI, −0.073 to 0.759]; P < 0.001). 13 Therefore, if the aim is to establish whether a particular cutoff concentration of a TNF antagonist has been reached as part of a TDM approach, it is always recommended to select the assay that was initially used to establish the respective threshold.…”

Section: Tdm Of Tnf Antagonists In CDmentioning

confidence: 99%

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Crohn Disease: A Theoretical Construct to Apply Pharmacokinetics and Guidelines to Clinical Practice

Casteele

Feagan

Wolf

et al. 2020

Inflammatory Bowel Diseases

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Therapeutic drug monitoring (TDM) is the measurement of drug and antidrug antibody concentrations in individuals to guide treatment decisions. In patients with Crohn disease (CD), TDM, used either reactively or proactively, is emerging as a valuable tool for optimization of tumor necrosis factor (TNF) antagonist therapy. Reactive TDM is carried out in response to treatment failure, whereas proactive TDM involves the periodic monitoring of patients responding to TNF antagonist therapy to allow treatment optimization. In patients with CD, most of the available data for TDM relate to the first-to-market TNF antagonist infliximab and, to a lesser extent, to adalimumab and certolizumab pegol. Several gastroenterology associations, including the American Gastroenterology Association, have endorsed the use of reactive TDM in patients with active CD. However, fewer recommendations currently exist for the use of proactive TDM, although several new prospective randomized controlled trials evaluating proactive TDM strategies have been published. In this review, the current evidence for reactive and proactive TDM is discussed, and a proactive treatment algorithm for certolizumab pegol based on previously published threshold concentrations is proposed.

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Infliximab and Adalimumab Concentrations May Vary Between the Enzyme-Linked Immunosorbent Assay and the Homogeneous Mobility Shift Assay in Patients With Inflammatory Bowel Disease: A Prospective Cross-Sectional Observational Study

Abstract: This prospective observational study including consecutive patients with inflammatory bowel disease treated with either infliximab or adalimumab showed that although the correlation between the ELISA and the homogeneous mobility shift assay was good for both drugs, the agreement was poor.

Cited by 14 publications

References 5 publications

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn’s Disease

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn’s Disease

Clinical Impact of Corrections to Infliximab and Adalimumab Monitoring Results with the Homogeneous Mobility Shift Assay

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Crohn Disease: A Theoretical Construct to Apply Pharmacokinetics and Guidelines to Clinical Practice

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