scholarly journals Quantitative Evaluations of Time-Course and Treatment Effects of Systemic Agents for Psoriasis: A Model-Based Meta-Analysis

2017 ◽  
Vol 102 (6) ◽  
pp. 1006-1016 ◽  
Author(s):  
T Checchio ◽  
S Ahadieh ◽  
P Gupta ◽  
J Mandema ◽  
L Puig ◽  
...  
Keyword(s):  
Time Course ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Model Based ◽  
Systemic Agents ◽  
Quantitative Evaluations

scholarly journals Model-based meta-analysis to optimise S. aureus-targeted therapies for atopic dermatitis

2021 ◽  
Author(s):  
Takuya Miyano ◽  
Alan D Irvine ◽  
Reiko J Tanaka
Keyword(s):  
Clinical Trials ◽  
Atopic Dermatitis ◽  
Targeted Therapies ◽  
Time Course ◽  
Model Simulation ◽  
Meta Analysis ◽  
Poor Responders ◽  
Coagulase Negative Staphylococcus ◽  
Model Based ◽  
Severity Scores

Background: Several clinical trials of Staphylococcus aureus (S. aureus)-targeted therapies for atopic dermatitis (AD) have demonstrated conflicting results regarding whether they improve AD severity scores. This study performs a model-based meta-analysis to investigate possible causes of these conflicting results and suggests how to improve the efficacies of S. aureus-targeted therapies. Methods: We developed a mathematical model that describes systems-level AD pathogenesis involving interactions between S. aureus and Coagulase Negative Staphylococcus (CoNS). The model was calibrated to reproduce time course data of S. aureus levels, EASI scores, and EASI-75 in response to dupilumab, S. hominis A9 (ShA9) and flucloxacillin from published clinical trials. We simulated efficacies of hypothetical S. aureus-targeted therapies on virtual patients using the model. Results: Our model simulation reproduced the clinically observed detrimental effects that application of ShA9 and flucloxacillin had on AD severity and showed that these effects disappeared if the bactericidal activity against CoNS was removed. A hypothetical (modelled) eradication of S. aureus by 3.0 log10 CFU/cm2, without killing CoNS, achieved comparable EASI-75 to dupilumab. This efficacy was potentiated if dupilumab was administered in conjunction with S. aureus eradication (EASI-75 at week 16; S. aureus eradication: 66.7%, dupilumab 61.6% and combination: 87.8%). The improved efficacy was also seen for virtual dupilumab poor responders. Conclusion: Our model simulation suggests that killing CoNS worsens AD severity and that S. aureus-specific eradication without killing CoNS could be effective for AD patients, including dupilumab poor responders. This study will contribute to design promising S. aureus-targeted therapy.

scholarly journals Model-Based Network Meta-Analysis for Time Course Relationships: A Union of two Methodologies

2018 ◽  
Vol 21 ◽  
pp. S224
Author(s):  
H Pedder ◽  
M Boucher ◽  
S Dias ◽  
M Bennetts ◽  
NJ Welton
Keyword(s):  
Time Course ◽  
Meta Analysis ◽  
Model Based

scholarly journals Performance of model‐based network meta‐analysis (MBNMA) of time‐course relationships: A simulation study

2020 ◽  
Author(s):  
Hugo Pedder ◽  
Martin Boucher ◽  
Sofia Dias ◽  
Margherita Bennetts ◽  
Nicky J. Welton
Keyword(s):  
Simulation Study ◽  
Time Course ◽  
Meta Analysis ◽  
Model Based

Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans

2020 ◽  
Vol 21 (5) ◽  
pp. 390-399
Author(s):  
Suhaila Omar Alhaj-Suliman ◽  
Gary Milavetz ◽  
Aliasger Karimjee Salem
Keyword(s):  
Adverse Events ◽  
Time Course ◽  
Meta Analysis ◽  
New Drugs ◽  
Maximum Effect ◽  
Primary Efficacy ◽  
Primary Efficacy Endpoint ◽  
Efficacy And Safety ◽  
Model Based ◽  
Osteoarthritic Pain

Background: Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA). Methods: To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach. Results: The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses. Conclusions: This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.

Therapeutic Benefit of Eletriptan Compared to Sumatriptan for the Acute Relief of Migraine Pain — Results of a Model-Based Meta-Analysis that Accounts for Encapsulation

Cephalalgia ◽  
2005 ◽  
Vol 25 (9) ◽  
pp. 715-725 ◽  
Author(s):  
JW Mandema ◽  
E Cox ◽  
J Alderman
Keyword(s):  
Pain Relief ◽  
Time Course ◽  
Meta Analysis ◽  
Therapeutic Benefit ◽  
Absolute Difference ◽  
Multiple Time ◽  
Model Based ◽  
Migraine Pain ◽  
Absolute Benefit ◽  
Significant Difference

A novel model-based meta-analysis was used to quantify the dose-response relationship of sumatriptan and eletriptan for the proportion of patients that achieve migraine pain relief up to 4h after treatment. The proportion of patients that became pain free was also evaluated. This analysis includes some unique features, allowing comparison of sumatriptan and eletriptan doses that have not been directly compared in a head to head study and also permitting comparison between the two drugs at multiple time points up to 4 h after treatment. Because the analysis allows comparison of response to blinded sumatriptan with that to marketed sumatriptan and contains timepoints as early as 0.5 h, it is especially suited to detection of possible effects of encapsulation on sumatriptan's therapeutic effectiveness and thus was employed to assess this also. Data from 19 randomized placebo controlled clinical trials were jointly analysed using a random-effects logistic regression model. The results of this analysis show a significant clinical benefit of eletriptan 40 mg compared to sumatriptan 100 mg at any point in time up to 4 h after treatment. The benefit of eletriptan 40 mg is greatest around 1.5-2 h after treatment with an absolute difference at 2 h of 9.1% (7.4-11.5%) more patients achieving pain relief and 7.3% (5.8-8.6%) more patient achieving pain free when compared to sumatriptan 100 mg. An absolute benefit of more than 5% of patients is maintained from 45 min up to 4 h after treatment for pain relief and from 1.5 h up to 4 h for pain free. Eletriptan 20 mg was superior to sumatriptan 50 mg and similar to sumatriptan 100 mg for pain relief while it was similar to sumatriptan 50 mg for pain free. The benefit of eletriptan 20 mg when compared to sumatriptan 50 mg is greatest around 1.5-2 h after treatment with an absolute difference at 2 h of 5.0% (2.9-8.1%) more patients achieving pain relief. An absolute benefit of more than 3% of patients was maintained from 1 h up to 3 h after treatment. No significant difference was found between eletriptan 20 mg and sumatriptan 50 mg for the fraction of patients that became pain free. No significant effect of encapsulation of sumatriptan was found on the time course of response up to 4 h after treatment when compared to commercial sumatriptan.

Sign in / Sign up

Export Citation Format

Share Document