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.
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 to give quantitative results. Studies have shown that the results using the rapid method are comparable to the traditional ELISA result.
“It is a good alternative for the conventional ELISA method for the measurement of IFX serum concentrations at trough in IBD”
“This rapid test strategy has the potential to reduce patient risks and improve patient outcomes without negative cost implications”
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 15 – All 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%).
Statement 92 – We 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
Infliximab
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:
Successful Routine Use of Quantum Blue® Therapeutic Drug Monitoring (TDM) Assays in an Italian Children Hospital
An interview with Dr. ssa Giuliana Cangemi
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
The new biosimilar of infliximab SB2 can be quantified by IFX-optimized therapeutic drug monitoring assays
Afonso et al. ECCO 2018
Therapeutic drug monitoring of CT-P13: a comparison of four different immunoassays
Afonso et al. Aug 17
Clinical performance of an infliximab rapid quantification assay
Magro et al. Aug 17
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.
Adalimumab
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.
Successful Routine Use of Quantum Blue® Therapeutic Drug Monitoring (TDM) Assays in an Italian Children Hospital
An interview with Dr. ssa Giuliana Cangemi
Serum levels of infliximab and adalimumab biosimilars can be measured equivalently to originator drugs by Quantum Blue® rapid testing as tool for therapeutic drug monitoring
Anchling et al. UEGW 2021
Performance Of the Bühlmann Quantum Blue® Adalimumab Rapid Test Dedicated For Therapeutic Drug Monitoring of Serum Adalimumab Trough Levels
Wieser et al UEGW P1014
Performance of QB Adalimumab Rapid Test for TDM of Serum Adalim Trough Levels
Wieser et al. UEGW P1014
Therapeutic Drug Monitoring
References Summary