Evaluation of dose-tapering strategies for intravenous tocilizumab in rheumatoid arthritis patients using model-based ph
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PHARMACOKINETICS AND DISPOSITION
Evaluation of dose-tapering strategies for intravenous tocilizumab in rheumatoid arthritis patients using model-based pharmacokinetic/pharmacodynamic simulations Carla Bastida 1,2 & Alwin D.R. Huitema 2,3 & Merel J. l’Ami 4 & Virginia Ruiz-Esquide 5 & Gerrit Jan Wolbink 4,6 & Raimon Sanmartí 5 & Dolors Soy 1,7 Received: 29 August 2019 / Accepted: 1 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Tocilizumab is a humanized monoclonal antibody approved for rheumatoid arthritis treatment. In clinical practice, empirical dose-tapering strategies are implemented in patients showing sustained remission or low disease activity (LDA) to avoid overtreatment and reduce costs. Since rational adaptive-dosing algorithms taking the full pharmacokinetic (PK)/pharmacodynamic (PD) characteristics into account are currently lacking, we aimed to develop novel tapering strategies and compare them with currently used empirical ones. Methods Four strategies were simulated on a virtual population. In all of them, the same initial dose was administered every 28 days for six consecutive months. Then, different strategies were considered: (1) label-dosing; (2) mild empirical dose-tapering; (3) intense empirical dose-tapering; (4) therapeutic drug monitoring (TDM)-guided dose-tapering. The different strategies were evaluated on the proportion of patients who maintain remission/LDA 1 year after the intervention. Cost-savings of direct drug costs were also estimated as relative dose intensity. Results The overall proportion of simulated patients in remission/LDA after 1 year of the intervention was comparable between the mild empirical and the TDM-guided dose-tapering strategies, and much lower for the intense empirical dose-tapering strategy (80.3%, 78.2%, and 69.0%, respectively). Likewise, 1-year flare rates were lower for the mild empirical and TDM-guided tapering strategies. The relative dose intensity was lowest for the intense empirical dose-tapering, followed by the TDMguided and the mild empirical dose-tapering approaches (61.2%, 71.0%, and 80.4%, respectively). Conclusion We demonstrated that the TDM-guided strategy using model-based algorithms performed similarly to mild empirical dose-tapering strategies in overall remission/LDA rates but is superior in cost-savings. Keywords Dose-tapering . Pharmacokinetics . Rheumatoid arthritis . Therapeutic drug monitoring . Tocilizumab
* Carla Bastida [email protected] 1
Pharmacy Department, Division of Medicines, Hospital Clinic Barcelona, Universitat de Barcelona, Villarroel 170, 08036 Barcelona, Spain
2
Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX Amsterdam, The Netherlands
3
Department of Clinical Pharmacy, University Medical Center, Utrecht University, Utrecht, The Netherlands
4
Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands
5
Arthritis Unit, Rheumatology Department, Hospital Clinic Barcelona, Universitat de
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