Leading Edge 2021 Issue 1

8 LEADING EDGE - 2021-1 Why Wait for Results? The Benefits of Rapid and Point-of-Care Monitoring of Therapeutic Drugs Biochemical testing to support clinical decision making is essential, but certain analytes are still not routinely tested in-house. For these, patient samples are sent away to a referral laboratory for analysis or are stored and batch tested once or twice a week. This means that it can take several weeks before a result is available and treatment decisions often have to be made without the benefit of that analyte information. In these situations rapid testing within the laboratory or even Point-of-Care (POC) testing can aid the management of patients significantly, by enabling rapid implementation of the appropriate treatment. In addition to the healthcare benefits, POC testing also gives significant benefits to patients, enabling direct discussion of results and the determination of an appropriate treatment plan immediately. Both of these can significantly relieve patient anxiety that the delays from traditional laboratory testing can cause. Rapid Drug Monitoring Knowledge of 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)1 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 20182, 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 [Figure 1]. In the absence of timely trough level information these patients are likely to receive subsequent doses without the appropriate adjustment, therefore compounding the situation. Figure 1: Proportion of patients with therapeutic IFX levels increased over time.2 Standardisation There are numerous tests available for the determination of trough level biologics and the World Health Organisation (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 correlation3 [Figure 2]. Another poster presented at the 2020 Virtual UEGW from R. Olson et al. compared the BÜHLMANN rapid infliximab assay with laboratory HPLC tandem mass spectrometry analysis performed at the Mayo Clinic in America4 with results giving an r of 0.965 [Figure 3]. Figure 2: Passing-Bablok regression analysis of serum samples analysed with BÜHLMANN and WHO calibration.3 Figure 3: Passing-Bablok regression analysis comparing BÜHLMANN rapid infliximab assay with laboratory HPLC tandem mass spectrometry analysis.4