ArticleJournal of pharmacokinetics and pharmacodynamics2008
Exposure-response modeling using latent variables for the efficacy of a JAK3 inhibitor administered to rheumatoid arthritis patients.
Article in Journal of pharmacokinetics and pharmacodynamics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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Who cites it
36 citing papers in PubMed.
- Early exposure-response modeling of an interferon-beta monoclonal antibody (dazukibart) in adults with dermatomyositis.Journal of pharmacokinetics and pharmacodynamics · 2026Trial
- Application of Beta-Distribution and Combined Uniform and Binomial Methods in Longitudinal Modeling of Bounded Outcome Score Data.The AAPS journal · 2020Trial
- Model-Based Characterization of the Pharmacokinetics, Target Engagement Biomarkers, and Immunomodulatory Activity of PF-06342674, a Humanized mAb Against IL-7 Receptor-α, in Adults with Type 1 Diabetes.The AAPS journal · 2020Trial
- Joint longitudinal model development: application to exposure-response modeling of ACR and DAS scores in rheumatoid arthritis patients treated with sirukumab.Journal of pharmacokinetics and pharmacodynamics · 2018Trial
- Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.Journal of pharmacokinetics and pharmacodynamics · 2017Trial
- Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab.British journal of clinical pharmacology · 2016Trial
- Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.Journal of clinical pharmacology · 2016Trial
- Latent variable indirect response modeling of categorical endpoints representing change from baseline.Journal of pharmacokinetics and pharmacodynamics · 2013Trial
- Lack of effect of tofacitinib (CP-690,550) on the pharmacokinetics of the CYP3A4 substrate midazolam in healthy volunteers: confirmation of in vitro data.British journal of clinical pharmacology · 2012Trial
- Informative dropout modeling of longitudinal ordered categorical data and model validation: application to exposure-response modeling of physician's global assessment score for ustekinumab in patients with psoriasis.Journal of pharmacokinetics and pharmacodynamics · 2011Trial
- A latent variable approach for modeling categorical endpoints among patients with rheumatoid arthritis treated with golimumab plus methotrexate.Journal of pharmacokinetics and pharmacodynamics · 2010Trial
- Implications of Immunogenicity Testing for Therapeutic Monoclonal Antibodies: A Quantitative Pharmacology Framework.The AAPS journal · 2024Article
- Moving Beyond Boundaries: Utilization of Longitudinal Exposure-Response Model for Bounded Outcome Score to Inform Decision Making in the Accelerated Drug Development Paradigm.Clinical pharmacokinetics · 2024Article
- A framework for precision "dosing" of mental healthcare services: algorithm development and clinical pilot.International journal of mental health systems · 2023Article
- Latent variable indirect response modeling of clinical efficacy endpoints with combination therapy: application to guselkumab and golimumab in patients with ulcerative colitis.Journal of pharmacokinetics and pharmacodynamics · 2023Article
- Role of Disease Progression Models in Drug Development.Pharmaceutical research · 2022Review
- Improving categorical endpoint longitudinal exposure-response modeling through the joint modeling with a related endpoint.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Pharmacometric analysis linking immunoglobulin exposure to clinical efficacy outcomes in chronic inflammatory demyelinating polyneuropathy.CPT: pharmacometrics & systems pharmacology · 2021Article
- Therapeutic Drug Monitoring for Current and Investigational Inflammatory Bowel Disease Treatments.Journal of clinical gastroenterology · 2021Review
- Facilitating Longitudinal Exposure-Response Modeling of a Composite Endpoint Using the Joint Modeling of Sparsely and Frequently Collected Subcomponents.The AAPS journal · 2020Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, no general methods have been developed to relate pharmacologically based models, such as indirect response models, to discrete or ordered categorical data. We propose the use of an unobservable latent variable (LV), through which indirect response models can be linked with drug exposure. The resulting indirect latent variable response model (ILVRM) is demonstrated using a case study of a JAK3 inhibitor, which was administered to patients in a rheumatoid arthritis (RA) study. The clinical endpoint for signs and symptoms in RA is the American College of Rheumatology response criterion of 20%--a binary response variable. In this case study, four exposure-response models, which have different pharmacological interpretations, were constructed and fitted using the ILVRM method. Specifically, two indirect response models, an effect compartment model, and a model which assumes instantaneous (direct) drug action were assessed and compared for their ability to predict the response data. In general, different model interpretations can influence drug inference, such as time to drug effect onset, as well as affect extrapolations of responses to untested experimental conditions, and the underlying pharmacology that operates to generate key response features does not change because the response was measured discretely. Consideration of these model interpretations can impact future study designs and ultimately provide greater insight into drug development strategies.
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Registered trials
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.