The TAXIT study by KU Leuven demonstrated the positive effect of the therapeutic drug monitoring of infliximab with regards to cost savings and therapy optimisation. R-Biopharm develops products and processes to optimise TDM.

Tumour necrosis factor (TNF) inhibitors are biologic agents used for the treatment of inflammatory diseases such as ulcerative colitis, Crohn’s disease and rheumatoid arthritis. Infliximab (IFX, trade name Remicade), its biosimilars Remsima and Inflectra, and adalimumab (trade name Humira) belong to this group of drugs.

When an inflammation begins, cells of the immune system increase the production of TNF. TNF binds to specific receptors, which trigger the signal for the inflammatory process. In the case of chronic inflammation, the immune system continuously produces TNF so that the inflammatory process is kept upright.

TNF inhibitors interrupt this cycle by binding to the messenger TNF. The molecule can no longer bind to the receptor, so the signalling cascade of the inflammatory process is disrupted. As a result, the inflammation and its symptoms can decrease, or cease completely.

Monitor to optimise

Individual dose adjustments can be made to optimise therapeutic drug monitoring (TDM), by measuring drug levels and immunogenicity. In order for drugs to work optimally, it is important to check the trough level of TNF inhibitors on a regular basis, since the bioavailability differs from person to person. For this purpose, the IFX drug concentration in the blood is tested shortly before the subsequent infusion (see figure, above right).

Immunogenicity also has an impact on the efficacy of the drug. So-called anti-drug antibodies (ADAs) bind to the drug and can lead to a decrease in drug availability in the metabolism, as well as allergic reactions. The monitoring of drug and ADA levels of TNF inhibitors helps to optimally adjust the therapy to the individual needs of the patient.

TDM of infliximab based on algorithm

The trough-level adapted infliximab treatment (TAXIT) algorithm is recommended for therapy adaptation (concerning dosage and interval) based on the results of ADA levels of infliximab. The algorithm is a result of Vande Casteele et al’s 2015 study in Gastroenterology, which investigated the effect of drug monitoring on the outcome of TNF treatment (see figure, below).

Vande Casteele et al’s study shows the positive effect of TDM for therapy optimisation and treatment cost reduction. R-Biopharm’s RIDASCREEN IFX Monitoring and anti-IFX antibodies are based on the assays used in this study.