TNF-α Antagonist

Obesity, an epidemic of our times with rates rising to alarming levels, is associated with comorbidities including cardiovascular diseases, arthritis, certain cancers, and degenerative diseases of the brain and other organs. Importantly, obesity is a leading cause of insulin resistance and type 2 diabetes. As emerging evidence has shown over the last decade, inflammation is one of the critical processes associated with the development of insulin resistance, diabetes and related diseases, and obesity is now considered as a state of chronic low-grade inflammation. Adipose tissue, apart from its classical role as an energy storage depot, is also a major endocrine organ secreting many factors, whose local and circulating levels are affected by the degree of adiposity. Obesity leads to infiltration of the expanded adipose tissue by macrophages and increased levels in proinflammatory cytokines. The first indication for increased cytokine release in obesity was provided by the identification of increased expression of TNF-alpha, a proinflammatory cytokine, in the adipose tissue of obese mice in the early 1990s. TNF-alpha is expressed in and secreted by adipose tissue, its levels correlating with the degree of adiposity and the associated insulin resistance. Targeting TNF-alpha and/or its receptors has been suggested as a promising treatment for insulin resistance and type 2 diabetes. This review will summarize the available knowledge on the role of TNF-alpha in obesity and related processes and the potential implications of the above in the development of new therapeutic approaches for obesity and insulin resistance. Recent data from clinical studies will also be described together with late findings on the pathogenesis of obesity and insulin resistance.

Tumor necrosis factor-α (TNF-α) blockers are a popular therapeutic choice in a number of inflammatory diseases. Thus far, five TNF- α blockers have been approved for clinical use (etanercept, infliximab, adalimumab, golimumab. and certolizumab). Despite being considered relatively safe, serious side effects associated with immune suppression have been reported, including central and peripheral nervous system (CNS) demyelinating disorders. It is still elusive whether these events are mere coincidence or a side effect of anti-TNF-α use. In this paper, we review the published case reports of CNS demyelination associated with anti-TNF-α therapy and present the follow-up of our 4 previously reported patients who developed neurologic symptoms suggestive of CNS demyelination after having received anti-TNF-α treatment. We also discuss the possible role of TNF-α blockers in demyelination.

Since the introduction of tumor necrosis factor (TNF)-α inhibitors, the treatment of rheumatoid arthritis (RA) has been revolutionized. The approach of targeting TNF-α has considerably improved the success in the treatment of RA. Over the last 3 decades five different TNF-α inhibitors have been administered: infliximab, etanercept, adalimumab, golimumab, and certolizumab-pegol. All of them show excellent efficacy with similar rates of clinical response and prevention of radiographic disease progression. With improved therapies, treatment strategies have also changed, with the aims now being to achieve and maintain remission. Most recently, the discussion expands to the issue of treatment reduction in patients who have achieved sustained remission; here, the discontinuation of TNF-α inhibitor therapy has become an area of interest, given obvious economic and risk-benefit evaluations. However, only little is known if "biologic free" remission is possible in patients with sustained remission following intensive TNF-α inhibitor therapy.