Background/Purpose:

The purpose is to develop an individualised treatment strategy based on Therapeutic drug monitoring (TDM) in order to optimise efficacy of Infliximab (INX) treatment. Targeted therapies have greatly improved the treatment of patients inflammatory joint diseases, but a significant proportion of patients either do not respond sufficiently to therapy or loose efficacy over time. An extensive individual variation in serum drug concentrations suggests both under- and overtreatment of a substantial proportion of patients. Many patients develop anti-drug antibodies (ADAb) during therapy, contributing to reduced drug levels, inefficacy and adverse events. TDM can probably increase effectiveness of treatment with INX and other biological drugs.

Methods:

The treatment strategy has been developed by the steering committee of the NORwegian DRUg Monitoring study (NOR-DRUM), based on a systematic literature research (SLR), unpublished data and expert opinion. A SLR was performed in May 2016. In Norway neutralising ADAb are measured with an “in house” assay. For this assay, ADAb levels >50 µg/L are defined as “high”. This cut-off is based on own s-INX and ADAb data (Diakonhjemmet Hospital during 2015-2016) and clinical experience. The proposed strategy has been developed through a series of meetings in the project group consisting of national leading experts in this field (both clinicians experienced with TDM and laboratory physicians) and with additional input from international key experts in the scientific advisory board of the NOR-DRUM study.

Results:

The treatment strategy from infusion number 4 onwards is depicted in the Figure. The therapeutic range for serum INX (through levels) is defined as 3-8µg/ml (Figure, green zone). During the induction phase (infusion 1-3) the recommendation is to keep the level >20 µg/ml at infusion 2 and >15µg/ml at infusion 3. A guideline for action according to levels outside the therapeutic range is given in the Figure. If the patients develop high levels of ADAb the recommendation is to switch therapy.

Conclusion:

An individualised treatment strategy based on TDM has the potential to optimise therapy with infliximab and other biological drugs by; 1) prevention of treatment failure by identification of patients with drug levels below the therapeutic range, 2) reduction of overtreatment, which predispose to side effects and increase costs, and 3) early identification of ADAb development, with the possibility to detect treatment failures prior to a clinical flare and to prevent hypersensitivity reactions. The real life efficacy of this strategy is being investigated in an ongoing randomised clinical trial, NOR-DRUM (NCT03074656).