scholarly journals TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200099
Author(s):  
Juliane Totzke ◽  
Scott A. Scarneo ◽  
Kelly W. Yang ◽  
Timothy A. J. Haystead
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Factor Inhibitor ◽  
Irritable Bowel ◽  
Inflammatory Signalling ◽  
Necrosis Factor

Aberrant tumour necrosis factor (TNF) signalling is a hallmark of many inflammatory diseases including rheumatoid arthritis (RA), irritable bowel disease and lupus. Maladaptive TNF signalling can lead to hyper active downstream nuclear factor (NF)-κβ signalling in turn amplifying a cell's inflammatory response and exacerbating disease. Within the TNF intracellular inflammatory signalling cascade, transforming growth factor-β-activated kinase 1 (TAK1) has been shown to play a critical role in mediating signal transduction and downstream NF-κβ activation. Owing to its role in TNF inflammatory signalling, TAK1 has become a potential therapeutic target for the treatment of inflammatory diseases such as RA. This review highlights the current development of targeting the TNF-TAK1 signalling axis as a novel therapeutic strategy for the treatment of inflammatory diseases.

scholarly journals Therapeutic drug monitoring of tumour necrosis factor inhibitors in the management of chronic inflammatory diseases

2018 ◽  
Vol 56 (1) ◽  
pp. 28-41 ◽  
Author(s):  
JG Sanchez-Hernandez ◽  
N Rebollo ◽  
F Munoz ◽  
A Martin-Suarez ◽  
MV Calvo
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Tumour Necrosis Factor ◽  
Drug Monitoring ◽  
Tumour Necrosis ◽  
Inflammatory Diseases ◽  
Tumour Necrosis Factor Inhibitor ◽  
Therapeutic Drug ◽  
Factor Inhibitor ◽  
Antidrug Antibodies ◽  
Necrosis Factor

Tumour necrosis factor inhibitor therapy has drastically changed the management of chronic inflammatory diseases. Some important drawbacks that can cause loss of response during treatment with these drugs are related to their large individual variability, the disease burden and the formation of antidrug antibodies that increase its clearance. Therapeutic drug monitoring of these drugs is not yet recommended by all scientific societies, and if so, only in patients with inflammatory symptoms. Proactive therapeutic drug monitoring represents a new strategy with many potential clinical benefits, including the prevention of immunogenicity, a reduction in the need for rescue therapy and greater durability of tumour necrosis factor inhibitor treatment. The review is based on a systematic search of the literature for controlled trials, systematic reviews, experimental studies, guideline papers and cohort studies addressing the best practice in tumour necrosis factor inhibitor therapeutic drug monitoring. Although there is ample evidence supporting the use of therapeutic drug monitoring in clinical practice to achieve better outcomes, some challenges have been detected. Many studies are focused on finding solutions for the lack of standardization of analytical methods to measure tumour necrosis factor inhibitor and antidrug antibodies concentrations. Other challenges are development of effective cost-saving proactive algorithms to identify optimal drug concentrations and the research on the role of antidrug antibodies, especially in the management and prevention of loss of response. Therapeutic drug monitoring of tumour necrosis factor inhibitor offers a rational approach to the optimization of the treatment of chronic inflammatory disease. Although prospective controlled trials yield little conclusive evidence of its benefits, there is growing acceptance of its value in clinical practice.

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