Table 1

EULAR-endorsed overarching principles and points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases

Grade of recommendationLevel of evidenceLevel of agreement (0–10, mean (SD))% of votes≥8/10
Overarching principles
APharmacokinetic and pharmacodynamic principles underpin the interpretation of TDM for biopharmaceuticalsNANA9.7 (0.9)100
BTDM refers to the principle of utilising pharmacokinetic data (biopharmaceutical blood concentrations and, optionally, ADAb, to optimise treatment for an individual patientNANA9.7 (0.5)100
CThere are two broad categories of TDM: Proactive TDM refers to scheduled testing irrespective of the clinical situation and reactive TDM refers to testing in response to particular clinical scenariosNANA9.7 (0.5)100
DMost research in the field relates to TNF-inhibitors but the underlying principles can be extrapolated to other biopharmaceutical classesNANA8.4 (1.4)76
ETherapeutic approaches to treating patients with inflammatory RMDs should be in line with international and national guidelines for the management of the respective disease. Consideration of TDM should be taken within the context of such guidanceNANA9.5 (1.1)96
FTDM should be part of a shared decision making process between the patient and healthcare professionals, incorporating the patient’s experiences and preferencesNANA9.5 (1.3)96
1Measurement of biopharmaceutical blood concentrations should be performed in a validated laboratoryC2b9.9 (0.3)100
2Measurement of ADAb should be performed in a validated laboratory, preferably using a consistent assay over time. Measurement should be performed and interpreted alongside contemporaneous biopharmaceutical blood concentrationsB - C2b9.8 (0.5)100
3Biopharmaceutical blood concentrations are dependent on the dose, administration interval and date of last dose. When interpreting biopharmaceutical blood concentrations, patient-specific factors that influence pharmacokinetics should be considered, which include body weight, methotrexate co-treatment, disease activity and adherence to therapyB2b9.6 (0.6)100
4Despite an association with clinical response, the use of biopharmaceutical blood concentrations to guide dosing is not recommended due to the lack of an identified optimal range for most biopharmaceuticals in most indications.B2b8 (2.2)72
5Routine use of proactive TDM is not recommended in the management of inflammatory RMDsD2b9 (1.6)88
6Measurement of biopharmaceutical blood concentrations up to 3 months after commencement of treatment could be considered to predict future efficacyB2b8.8 (1.3)92
7Reactive TDM could be considered in the management of inflammatory RMDsB2b9.5 (1.0)84
8Measurement of biopharmaceutical blood concentrations could be considered to identify those with high biopharmaceutical blood concentrations in whom tapering may be indicatedB2b9.3 (1.2)88
9Measurement of biopharmaceutical blood concentrations should be considered to understand clinical non-responseB2b9.5 (1.0)96
10Measurement of ADAb should be considered in the case of immunogenic biopharmaceuticals, alongside biopharmaceutical blood concentrations, at the time of clinical non-responseB2b9.4 (1.0)96
11Measurement of ADAb should be considered in the case of a hypersensitivity reaction, mainly related to infusionsB2b9.4 (1.4)96
12Measurement of ADAb is not recommended in the case of an injection-site reactionD58.8 (2.0)84
13Cost-effectiveness of TDM should be considered according to local context and standard of careD2c8.8 (2.4)80
  • ADAb, antidrug antibodies; NA, not applicable; RMDs, rheumatic and musculoskeletal diseases; TNF, tumour necrosis factor.