scholarly journals Role of IL-23 neutralization in psoriasis – insights from a mechanistic PK/PD model and meta-analysis of clinical data

2021 ◽  
Author(s):  
Georgi I. Kapitanov
Keyword(s):  
Mathematical Model ◽  
Monoclonal Antibodies ◽  
Patient Outcomes ◽  
Clinical Efficacy ◽  
Clinical Data ◽  
Meta Analysis ◽  
Current Work ◽  
Therapeutic Molecules ◽  
Dosing Regimens

AbstractBlocking of IL-23 has shown a profound effect on patient outcomes in psoriasis. The current IL-23 binding monoclonal antibodies show differences in dosing regimens, pharmacokinetics, affinity for the target, and efficacy outcomes in the clinic. The goal of the current work is to use a mechanistic pharmacokinetics/pharmacodynamics mathematical model to estimate projected free IL-23 neutralization for the different therapeutic molecules and connect it to clinical efficacy outcomes. The meta-analysis indicates a sigmoid-like relationship and suggests that the best current anti-IL23 antibodies are close to saturating the efficacy that can be achieved by this pathway in psoriasis.

scholarly journals The Prognostic Role of BRAF Mutation in Metastatic Colorectal Cancer Receiving Anti-EGFR Monoclonal Antibodies: A Meta-Analysis

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65995 ◽  
Author(s):  
Zi-Xu Yuan ◽  
Xiao-Yan Wang ◽  
Qi-Yuan Qin ◽  
De-Feng Chen ◽  
Qing-Hua Zhong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Braf Mutation ◽  
Meta Analysis ◽  
Prognostic Role

The misleading concept of initial severity in depression clinical trials: development and results from a mathematical model

2016 ◽  
Vol 25 (1) ◽  
pp. 18-20 ◽  
Author(s):  
Konstantinos N Fountoulakis
Keyword(s):  
Mathematical Model ◽  
Clinical Trials ◽  
Treatment Efficacy ◽  
Positive Relationship ◽  
Meta Analysis ◽  
True Nature ◽  
Patient Level ◽  
Initial Severity ◽  
Artificial Datasets

Objective: Recently, meta-analytic studies have suggested a positive relationship between initial severity and magnitude of treatment efficacy. The aim of the current study was to develop a mathematical model to test the assumption concerning the role of initial severity in treatment response. Methods: A number of experimental artificial datasets were developed on the basis of three different scenarios which reflect a pre-determined effect of initial severity. They were used to test for correlations at the patient level as well as at the meta-analysis level (trial level). Results: The results suggested that in all scenarios and analyses the correlations were so high that a ceiling effect was obvious. The testing concerned changes from baseline, but not differences between arms. Conclusions: Overall the data suggest that the question concerning the role of initial severity cannot be answered. Any allegations on such a role are based on flawed methodology and do not take into consideration the true nature of data.

scholarly journals Gabapentin

1996 ◽  
Vol 23 (S2) ◽  
pp. S10-S12 ◽  
Author(s):  
J. Bruni
Keyword(s):  
Antiepileptic Drug ◽  
Clinical Efficacy ◽  
Clinical Data ◽  
Mechanism Of Action ◽  
Clinical Studies ◽  
Adjunctive Therapy ◽  
Pharmacokinetic Profile ◽  
Seizure Models ◽  
Clonic Seizures

ABSTRACT:Gabapentin is a novel antiepileptic drug that has recently been introduced in Canada. Although its mechanism of action remains to be defined gabapentin is effective in a number of seizure models which predict its efficacy in partial and tonic-clonic seizures. Clinical studies support the clinical efficacy of gabapentin as adjunctive therapy in adults with epilepsy with partial and secondarily generalized tonic-clonic seizures. Gabapentin has a favorable pharmacokinetic profile and is generally well tolerated. More clinical data are required on the role of gabapentin in children and additional monotherapy experience is required before the role of gabapentin in the overall treatment of epilepsy can be better defined.

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