Six overarching principles and 13 European Alliance of Associations for Rheumatology (EULAR) points to consider were formulated for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs), according to a systemic literature review published in Annals of the Rheumatic Diseases.
A multidisciplinary task force comprising 11 rheumatologists, a bioanalytical scientist, a health economist with a background in clinical pharmacy, 3 patient representatives, and other experts representing 8 European countries convened to consensually formulate 13 research questions.
The task force performed literature searches from PubMed, Embase, and Cochrane, as well as relevant international congress (American College of Rheumatology and EULAR) abstracts from 2018 and 2019, and EULAR abstracts published through July 2020. Two different searches were performed: the first on the technical aspects of TDM, and the second on the clinical utility of TDM. The clinical aspects were confined to the RMDs in which TDM has been studied to date, which were adult patients with rheumatoid arthritis and spondyloarthritis, including psoriatic arthritis.
The points to consider are as follows:
- The manner in which biopharmaceutical blood concentrations were measured;
- Patient-specific factors that influence pharmacokinetics in relationship to dose, administration interval, and timing of last dose;
- The lack of identified optimal range for most biopharmaceuticals in most indications;
- The measurements of biopharmaceutical blood concentrations up to 3 months after first dose to predict future efficacy;
- The potential for reactive TDM in the management of inflammatory RMDs;
- The measurement of biopharmaceutical blood concentrations to better understand clinical nonresponse; and
- Economic analyses for improved use of resources.
The task force discussed preliminary overarching principles and points to consider after reviewing the SLR results. They then came to consensus via voting in accordance with the 2014 updated EULAR standardized operation procedures.
These points to consider may be potentially limited in generalizability, which depends on international guidelines on both patient management and on local context. Despite the existence of EULAR recommendations within Europe, differences regarding the use of biopharmaceuticals remain. The researchers indicated that future research and education should focus on stakeholder (ie, patients, rheumatologists, and other health professionals) preferences and acceptability regarding TDM of biopharmaceuticals.
The review authors concluded, “[T]hese are the first set of EULAR-endorsed overarching principles and points-to-consider advising on whether, when, in whom, and how to perform and interpret TDM of biopharmaceuticals in inflammatory RMDs in clinical practice. Given the rapidly progressing field of TDM and personalized medicine more broadly, it is anticipated that some of the unanswered questions highlighted in these points-to-consider will be answered, as more data become available, which may prompt for an update of these points-to-consider in the years ahead.”
Krieckaert CLM, van Tubergen A, Gehin JE, et al. EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases. Published online May 12, 2022. Ann Rheum Dis. doi: 10.1136/annrheumdis-2022-222155