scholarly journals Correction to: Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis

2020 ◽  
Vol 37 (3) ◽  
Author(s):  
Phyllis Chan ◽  
Jiajie Yu ◽  
Leslie Chinn ◽  
Marita Prohn ◽  
Jan Huisman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Population Pharmacokinetics ◽  
Meta Analysis ◽  
Response Analysis ◽  
Model Based ◽  
Exposure Response

scholarly journals Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis

2020 ◽  
Vol 37 (2) ◽  
Author(s):  
Phyllis Chan ◽  
Jiajie Yu ◽  
Leslie Chinn ◽  
Marita Prohn ◽  
Jan Huisman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Population Pharmacokinetics ◽  
Clinical Efficacy ◽  
Meta Analysis ◽  
Compartment Model ◽  
Phase 2 ◽  
Efficacy Data ◽  
Exposure Response ◽  
Phase 2 Clinical Trial

Abstract Purpose Fenebrutinib (GDC-0853), a Bruton’s tyrosine kinase (BTK) inhibitor was investigated in a Phase 2 clinical trial in patients with rheumatoid arthritis (RA). Our aim was to apply a model-informed drug development (MIDD) approach to examine the totality of available clinical efficacy data. Methods Population pharmacokinetics (popPK) modeling, exposure-response (E-R) analysis, and model-based meta-analysis (MBMA) of fenebrutinib were performed based on the Phase 2 data. Results PopPK of fenebrutinib after oral administration was described using a 3-compartment model with linear elimination and a flexible absorption transit compartment model. Healthy subjects had a 52% higher apparent clearance than patients. E-R analyses based on longitudinal ACR20, ACR50, and ACR70 and DAS28 (CRP) data modeled fenebrutinib effect with an Emax function, and an efficacy plateau was achieved within the exposure range obtained in the Phase 2 clinical trial. Based on literature data, a summary-level clinical efficacy database was constructed, and MBMA determined ACR20, ACR50, and ACR70 responder rates in the placebo and adalimumab arms of the Phase 2 clinical trial were found to be consistent with historical data for these treatments. Conclusions Our multi-pronged approach applied MIDD to maximize knowledge extraction of efficacy data and enabled robust interpretation from a Phase 2 clinical trial.

scholarly journals Model-based exposure-response analysis to quantify age related differences in the response to scopolamine in healthy subjects

2016 ◽  
Vol 82 (4) ◽  
pp. 1011-1021 ◽  
Author(s):  
Ricardo Alvarez-Jimenez ◽  
Geert Jan Groeneveld ◽  
Joop M. A. van Gerven ◽  
Sebastiaan C. Goulooze ◽  
Anne Catrien Baakman ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Response Analysis ◽  
Model Based ◽  
Exposure Response ◽  
Age Related

scholarly journals Occupational exposure to silica and risk of heart disease: a systematic review with meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e029653 ◽  
Author(s):  
Kai Liu ◽  
Min Mu ◽  
Kehong Fang ◽  
Yuanyuan Qian ◽  
Song Xue ◽  
...  
Keyword(s):  
Systematic Review ◽  
Heart Disease ◽  
Cohort Studies ◽  
Meta Analysis ◽  
Response Analysis ◽  
Study Quality ◽  
Silica Exposure ◽  
Pulmonary Heart Disease ◽  
Exposure Response ◽  
The Relationship

ObjectiveTo search for evidence of the relationship between occupational silica exposure and heart disease.DesignA systematic review and meta-analysis.BackgroundGrowing evidence suggests a relationship between occupational silica exposure and heart disease; however, the link between them is less clear.Data sourcesPubMed, ScienceDirect, Springer and EMBASE were searched for articles published between 1 January 1995 and 20 June 2019. Articles that investigated the effects of occupational silica exposure on the risk of heart disease were considered.Study selectionWe included cohort studies, including prospective, retrospective and retroprospective studies.Data extraction and synthesisWe extracted data using a piloted data collection form and conducted random-effects meta-analysis and exposure-response analysis. The meta-relative risk (meta-RR), a measure of the average ratio of heart disease rates in those with and without silica exposure, was used as an inverse variance-weighted average of relative risks from the individual studies. The Newcastle-Ottawa Quality Assessment Scale for cohort studies was used for study quality assessment.Outcome measureWe calculated the risk of heart diseases such as pulmonary heart disease, ischaemic heart disease and others.ResultsTwenty cohort studies were included. The results suggest a significant increase in the risk of overall heart disease (meta-RR=1.08, 95% CI 1.03 to 1.13). Stronger evidence of association with pulmonary heart disease was found in the risk estimate of both categories of heart disease (meta-RR=1.24, 95% CI 1.08 to 1.43) and in the exposure-response analysis (meta-RR=1.39, 95% CI 1.19 to 1.62). Our subgroup analyses also revealed that the statistical heterogeneity among studies could be attributed mainly to the diversity in reference group, occupation and study quality score.ConclusionsSilica-exposed workers are at an increased risk for overall heart disease, especially pulmonary heart disease. Further research is needed to better clarify the relationship between occupational silica exposure and ischaemic heart disease.PROSPERO registration numberCRD42019124673.

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