Evidence map›Paper›PMID 32514745›Full record

ArticleEuropean journal of clinical pharmacology2020

Evaluation of dose-tapering strategies for intravenous tocilizumab in rheumatoid arthritis patients using model-based pharmacokinetic/pharmacodynamic simulations.

Carla Bastida, Alwin D R Huitema, Merel J l'Ami, Virginia Ruiz-Esquide, Gerrit Jan Wolbink, Raimon Sanmartí, Dolors Soy

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in European journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Article
  4. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Carla BastidaPharmacy Department, Division of Medicines, Hospital Clinic Barcelona, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain. cbastida@clinic.cat.ORCID https://orcid.org/0000-0003-0845-8107
Alwin D R HuitemaDepartment of Pharmacy & Pharmacology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.
Merel J l'AmiRheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.
Virginia Ruiz-EsquideArthritis Unit, Rheumatology Department, Hospital Clinic Barcelona, Universitat de Barcelona, Barcelona, Spain.
Gerrit Jan WolbinkRheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.
Raimon SanmartíArthritis Unit, Rheumatology Department, Hospital Clinic Barcelona, Universitat de Barcelona, Barcelona, Spain.
Dolors SoyPharmacy Department, Division of Medicines, Hospital Clinic Barcelona, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain.

Funding

"la Caixa" Foundation 100010434
6 · The paper itself

Abstract

purposeTocilizumab 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.

methodsFour 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.

resultsThe 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 TDM-guided and the mild empirical dose-tapering approaches (61.2%, 71.0%, and 80.4%, respectively).

conclusionWe 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.

Indexed as

Models, BiologicalAdministration, IntravenousAlgorithmsAntibodies, Monoclonal, HumanizedAntirheumatic AgentsArthritis, RheumatoidComputer SimulationDrug TaperingHumansRemission InductionAntibodies, Monoclonal, HumanizedAntirheumatic AgentstocilizumabDose-taperingPharmacokineticsRheumatoid arthritisTherapeutic drug monitoringTocilizumab

Identifiers

PMID32514745

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.