TNFα Therapeutic Drug Monitoring

Therapeutic-Drug-Monitoring

Rapid Drug Monitoring

Serum trough levels for biologic drugs are extremely useful in determining effective treatment. These compounds are prone to either a primary loss of response (up to 30% of patients) or a loss of response over time (up to 46% of patients) with the level varying depending on the compound.

Historically, testing has been performed using ELISA methods which necessitates batch testing in order to be cost efficient but inevitably introduces a delay in obtaining the result. This is compounded by the fact that few hospitals run the analysis themselves – most use a referral service which means results can be delayed by several weeks.

Proportion of patients with therapeutic IFX levels increased over time

The optimal time to assess a drug level is immediately prior to the next infusion when it is at the trough level. Consequently, due to the time taken to obtain test results traditionally, patients will receive at least the immediate dose without adjustment. They may even receive multiple further doses before the drug can be optimised into the therapeutic window.

In a poster presented by C. Rentsch et al. at ECCO 2018, data showed 77% of patients required dose adjustment based on the serum trough levels achieved after the first dose, with 51% requiring dose reduction and 26% requiring dose escalation. (See graph on right)

In the absence of timely trough level information these patients are likely to receive subsequent doses without the appropriate adjustment, therefore compounding the situation.

BÜHLMANN Quantum Blue® Therapeutic Drug Monitoring Assays

The BÜHLMANN Quantum Blue® Infliximab and Adalimumab assays enable rapid, individual testing of serum samples to give trough level results in about an hour, enabling the proactive management of patients through adjustment of the next dose. Rapid results like these not only enable optimisation of treatment minimising loss of response and side effects but also save valuable healthcare resources.

The Quantum Blue therapeutic drug monitoring assays are read using a small bench top reader and can be performed in the laboratory or infusion clinic to give quantitative results. Studies have shown that the results using the rapid method are comparable to the traditional laboratory result:

“It is a good alternative for the conventional ELISA method for the measurement of IFX serum concentrations at trough in IBD”

Strik. A et al. ECCO 2018.

“This rapid test strategy has the potential to reduce patient risks and improve patient outcomes without negative cost implications

Strik. A et al. ECCO 2018.

The total test time is approximately one hour (actual assay time is 15 minutes). This makes it practical for patients to attend clinic, have their blood sample taken for analysis by the nurse in the infusion clinic and then whilst the patient goes for a cup of tea the assay can be run. The results are then available in time to optimise the dose given at that appointment. Tests can be performed in the laboratory, or by nurses in clinic and still have a good correlation to the laboratory result.

Antibody Testing

These drugs can suffer from loss of response due to the development of antibodies against the drug molecules. This can occur in up to 46% of patients (depending on the drug). So, in addition to the importance of determining if the drug level is within the therapeutic window, antibody levels should also be tested. Monitoring patients on treatment is also very important and therefore, anti-drug antibody assays are also available to determine the free antibody level within patients.

Following the same format as the drug level assays, the antibody assays will give a qualitative result within an hour enabling immediate adjustment of therapy if required.

Key Features

  • Serum trough drug levels:
    – Infliximab: 0.4 – 20µg/ml – Linear up to 180µg/ml
    – Adalimumab: 1.3 – 35µg/ml
  • Anti-drug antibody assays:
    – Anti-infliximab using a 0.2µgeq/ml cut-off
    – Anti-adalimumab using a 1.3µgeq/ml cut-off
  • Single use assay:
    – No need to batch samples
    – Individually packaged test
  • Available in two pack sizes
  • Assay time of 15 minutes (total test time 1 hour)
  • Correlation with traditional ELISA methods
  • Read using a simple touchscreen bench top reader

BSG Consensus Guidelines on the Management of Inflammatory Bowel Disease in Adults

Good Practice Recommendation 15All IBD patients should be reviewed 2–4 weeks after completing loading doses of anti-TNF therapy to assess response and optimise maintenance dosing based on clinical response and measures such as serum drug and anti-drug antibody concentrations, blood inflammatory markers, faecal biomarkers or endoscopy (Agreement: 82.5%).BSG

Statement 92We suggest that treatment options for failure of initial anti-TNF therapy (increase dose, shorten dosage interval, switch to alternative anti-TNF, or switch to different drug class) may be informed by the clinical context and by measurement of serum drug and anti-drug antibody concentrations (GRADE: weak recommendation, low-quality evidence. Agreement: 97.7%).

Statement 93 We suggest that patients with secondary loss of response to anti-TNF therapy may have serum drug and antidrug antibody concentrations measured to inform appropriate changes in treatment (GRADE: weak recommendation, moderate-quality evidence. Agreement: 97.6%).

Read the BSG Guidelines

The BÜHLMANN Quantum Blue® Infliximab assay is an immunoassay for the quantitative determination of infliximab trough levels in human serum which can be used to support therapy monitoring. Generally, trough levels in serum that reach a value of 3µg/ml and above correlate well with remission, endoscopic healing of the gut mucosa and low CRP values as well as prediction of sustained response to infliximab therapy.

The test is designed for the selective measurement of infliximab by a sandwich immunoassay.

Recombinant tumour necrosis factor alpha (TNFα) is conjugated to gold colloids. On the test cassette the conjugate is released from the pad onto the reaction system as the sample is applied. Infliximab present in the sample will bind to the conjugate. A highly specific monoclonal antibody is immobilised on the test membrane and will capture the conjugate/analyte complex, resulting in a colouring of the test line. The remaining free TNFα/gold conjugate will bind to the control line. The signal intensities of the test line and the control line are measured quantitatively by the BÜHLMANN Quantum Blue® reader.

There are numerous tests available for the determination of trough level biologics and the WHO has recently introduced an international reference material for infliximab (NIBSC 16/170) to improve comparability of the various testing methods.

A poster by Keller et al presented at the 2020 Virtual UEGW evaluated samples analysed with the BÜHLMANN Quantum Blue Infliximab assay and WHO calibration which showed excellent correlation:

Buy Online

Quantum Blue anti-TNFα Drug Monitoring
Product Code Description Pack Size
LF-TLIF25 Quantum Blue® Infliximab 25 Tests
LF-TLIF10 Quantum Blue® Infliximab 10 Tests
LF-ADIF25 Quantum Blue® Anti-infliximab Antibody 25 Tests
LF-ADIF10 Quantum Blue® Anti-infliximab Antibody 10 Tests

First successful comparison of Quantum Blue® rapid TDM assay standardization with WHO international standard for infliximab

Keller et al. UEG Virtual Week

High Correlation of the Quantum Blue® rapid assay with HPLC tandem mass spectrometry for infliximab therapeutic drug monitoring

Olson et al. UEG Virtual Week 2020

Quantum Blue® Anti-Infliximab: Development and evaluation of a point of care rapid test for measuring anti-infliximab antibodies in human serum

Bantleon et al. ECCO P202

Alfonso et al ECCO

The new biosimilar of infliximab SB2 can be quantified by IFX-optimized therapeutic drug monitoring assays

Afonso et al. ECCO 2018

The new infliximab point-of-care quantitative test can equally be used for therapeutic drug monitoring of biosimilars of infliximab

Afonso et al. Poster at ECCO 2018

ECCO-P767

Quantum Blue® Infliximab POC User Performance Evaluation

Fellay et al. ECCO 2018 Poster No. 767

Alfonso_TDM_CT-P13

Therapeutic drug monitoring of CT-P13: a comparison of four different immunoassays

Afonso et al. Aug 17

Magro-et-al

Clinical performance of an infliximab rapid quantification assay

Magro et al. Aug 17

QB-infliximab-poster

Patient-near Infliximab trough-level testing by a novel quantitative rapid test: The Quantum Blue Infliximab test

Lindsjø et al. Poster – UEG Week October 2016

QB-infliximab-paper

Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point-of-care quantitative test with two established ELISA assays

Afonso J et al. Aliment Pharmacol Ther. 2016 Oct;44(7):684-92

Infliximab_QB_Poster

Performance of the BÜHLMANN Quantum Blue® Infliximab point-of-care assay dedicated for therapeutic drug monitoring of serum infliximab trough levels

ECCO, March 16-19, 2016, Poster No. 242

TDM-References

Therapeutic Drug Monitoring

References Summary

BÜHLMANN Quantum Blue® Adalimumab is an in vitro diagnostic lateral flow immunoassay for the quantitative determination of trough levels of adalimumab in serum samples.

The assay serves as an aid to therapeutic drug monitoring in patients with inflammatory bowel disease (IBD) under adalimumab therapy, in conjunction with other clinical and laboratory findings. Quantum Blue Adalimumab is combined with the Quantum Blue Reader. The test is designed for the selective measurement of adalimumab by a sandwich immunoassay.

Recombinant tumor necrosis factor alpha (TNFα) is conjugated to gold colloids. On the test cassette the gold conjugate is released from a pad into the reaction system as the sample is applied. Adalimumab present in the sample will bind to the gold conjugate. A monoclonal antibody, highly specific for adalimumab, is immobilised on the analytical membrane and will capture the complex of gold conjugate and the adalimumab analyte, resulting in a colouring of the Test Line (T). The remaining free TNFα-gold conjugate will bind to the Control Line (C). The signal intensities of the Test Line (T) and the Control Line (C) are measured quantitatively by the Quantum Blue Reader.

Buy Online

Quantum Blue anti-TNFα Drug Monitoring
Product Code Description Pack Size
LF-TLAD25 Quantum Blue® Adalimumab 25 Tests
LF-TLAD10 Quantum Blue® Adalimumab 10 Tests
LF-ADAD25 Quantum Blue® Anti-adalimumab Antibody 25 Tests
LF-ADAD10 Quantum Blue® Anti-adalimumab Antibody 10 Tests

Quantum Blue® Anti-Adalimumab: Development and evaluation of a point of care rapid test for measuring anti-adalimumab antibodies in human serum

Ricken et al. ECCO 2019

ECCO-P283

Quantum Blue® Adalimumab: Development of the first point of care rapid test for therapeutic drug monitoring of serum adalimumab levels

Bantleon et al. ECCO P283

UEGW-P1014

Performance of QB Adalimumab Rapid Test for TDM of Serum Adalim Trough Levels

Wieser et al. UEGW P1014

TDM-References

Therapeutic Drug Monitoring

References Summary

Infliximab Assay Videos

BÜHLMANN Quantum Blue® Therapeutic Drug Monitoring Tutorial:
Demonstration of quantitative trough level measurement for therapeutic drug monitoring using the Quantum Blue® TDM rapid test technology.

TDM Success Story from convent hospital Barmherzige Brüder St. Veit Trailer:
Dr. Hans Peter Gröchenig from the convent hospital Barmherzige Brüder St. Veit talks about the successful introduction of Quantum Blue® TDM tests in an Austrian IBD Centre.

Joana Afonso from the University of Porto presents data that confirms the validated use of the Quantum Blue® Infliximab assay to quantify the new infliximab biosimilar SB2.

Dr. Afif from McGill presents a pilot study for the Quantum Blue® Infliximab rapid test application in loss of response patients.

Dr. Rentsch from the Alfred Health Melbourne shows very promising data on infliximab management supported by the Quantum Blue® Infliximab rapid test and implications for therapy cost reduction.

Dr. Maria Pia Santos from the Beatriz Angelo Hospital presents data on an easy integration of the Quantum Blue® TDM rapid test in clinical routine.

ECCO 2019

Updates from the ECCO Conference in Copenhagen on Therapeutic Drug monitoring

The 2019 European Crohn’s and Colitis Organisation conference in Copenhagen was extremely well attended by over 8000 participants (with the largest contingent being from the UK) which was a 20% increase in previous years. There were almost 900 posters which focused mainly on clinical diagnosis & outcomes and Clinical therapy & observations.

Below is a list of some of the posters on rapid drug monitoring using the BÜHLMANN Quantum Blue device:

P576: Therapeutic Drug Monitoring as a Predictive Marker of Mucosal Healing  in Crohn’s Disease Patients Treated with Anti-TNF: A Prospective Multicenter Study

L. Bertani, University of Pisa, Italy presented a poster at ECCO to see if monitoring serum trough levels of infliximab and adalimumab could predict mucosal healing (MH) or clinical remission (CR). They tested 35 Crohn’s disease patients (21 starting Adalimumab and 14 starting Infliximab) at 14, 22 and 54 weeks for the serum trough levels using the BÜHLMANN Quantum Blue rapid TDM assays and the Promonitor ELISA assay.

Trough level assessment, especially at week 22, could be very useful in the management of CD patients naïve to anti-TNFs treated with ADL. The good correlation with MH has an important clinical implication, as far as the disappearance of ulcers should be the target of anti-TNF therapy.”

Bertani-ECCO-2019_Graph2
Bertani-ECCO-2019_Graph1

“Moreover, POC assay has showed the same efficacy than ELISA and is quicker and easier to perform. In this perspective, a proactive management of TDM could be suggested, especially if the same results could be extended to IFX-treated patients. The study is ongoing, and the final results would suggest a wider use of TDM in CD patients.”

Click Here to Read the Poster Abstract from L. Bertani

P113: Accuracy of a New Rapid Test Assay for Monitoring Adalimumab Levels

J. Afonso, University of Porto, Spain also presented a poster at ECCO comparing the BÜHLMANN Quantum Blue rapid adalimumab assay to three ELISA based assays. They tested 120 IBD patient samples and some spiked samples:

Assay ICC (theoretical & measured) Recovery
BÜHLMANN Quantum Blue 0.982 86%
Immundiagnostik ELISA 0.927 111%
R-Biopharm ELISA 0.984 113%
In-house ELISA 0.989 110%

The new Quantum Blue Adalimumab assay, which is able to deliver results within 15 minutes, can safely replace the commonly used ELISA-based ADA quantification kits and it is reliable alternative to these methods. This new assay is perfect for immediate concentration adjusted dosing avoiding delays caused by ELISA assays with a turnaround time of approximately 8 hours.”

Click Here to Read the Poster Abstract from J. Afonso

P202: Quantum Blue® Anti-Infliximab: Development and evaluation of a point of care rapid test for measuring anti-infliximab antibodies in human serum

F. Bantleon from BÜHLMANN Laboratories presented a poster on anti-infliximab antibody assay on the Quantum Blue platform demonstrating a measuring range of 0.5 – 12µg/ml and an LOD of 0.31µg/ml.

“A clinical cut off value of 1.44µg/ml results in a sensitivity of 0.86 and a specificity of 0.94 obtained by ROC curve analysis with 78 patient samples:”

Click Here to View the Poster from F. Bantleon
Bantleon-ECCO_Graph

P153: Quantum Blue® Anti-Adalimumab: Development and evaluation of a point of care rapid test for measuring anti-adalimumab antibodies in human serum

B. Ricken from BÜHLMANN Laboratories presented a poster on anti-adalimumab antibody assay on the Quantum Blue platform demonstrating a preliminary measuring range of 0.3 – 12µg/ml. Using 119 patient serum samples, a preliminary cut-off value of 0.44µg/ml is proposed.

102 patient samples were also compared on both the Quantum Blue and the R-Biopharm ELISA demonstrating 87% agreement.

Click Here to View the Poster from B. Ricken
Ricken-ECCO_Graph1