Therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal disease: a systematic literature review informing EULAR points to consider.

The objectives of this review were to collect and summarise evidence on therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases and to inform the EULAR Task Force for the formulation of evidence-based points to consider. A systematic literature review (SLR) was performed, covering technical aspects and (clinical) utility of TDM, to answer 13 research questions. MEDLINE, Embase and Cochrane were searched until July 2020. American College of Rheumatology and EULAR abstracts were also considered for inclusion. Data were extracted in evidence tables and risk of bias assessment was performed. For the search on technical aspects, 678 records were identified, of which 22 papers were selected. For the clinical utility search, 3846 records were identified, of which 108 papers were included. Patient-related factors associated with biopharmaceutical blood concentrations included body weight, methotrexate comedication and disease activity. The identification of a target range was hampered by study variability, mainly disease activity measures and study type. Evidence was inconsistent for multiple clinical situations in which TDM is currently applied. However, for some particular scenarios, including prediction of future treatment response, non-response to treatment, tapering and hypersensitivity reactions, robust evidence was found. There is currently no evidence for routine use of proactive TDM, in part because published cost-effectiveness analyses do not incorporate the current landscape of biopharmaceutical costs and usage. This SLR yields evidence in favour of TDM of biopharmaceuticals in some clinical scenarios, but evidence is insufficient to support implementation of routine use of TDM.

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Competing interests: AvT received unrestricted research grants from Pfizer, Abbvie, Novartis, UCB and Biogen and consultancy fees from Novartis; AB received grant/research support and fees for consultancies or as a speaker from Abbvie, Amgen, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, UCB and Roche; MJ received travel expenses from Abbvie and speaker fees from Grifols in the last 5 years; DM acted as a consultant and gave lectures on behalf of his institution for Pfizer, Novartis and Grifols and was invited to attend an international congress by Janssen-Cilag; his institution received grants for research from the non-governmental organisation Lions Club Tours Val de France; VN-C received research grants/honoraria from AbbVie, Janssen, Lilly, Moonlake, Novartis, Pfizer and UCB; JDI received grant income from Pfizer, GSK and Janssen and consultancy/speaker fees/sponsorship from Abbvie, Eli Lily, Gilead, Roche and UCB.