2014
DOI: 10.1016/j.pharep.2014.05.004
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TNF inhibitors – Mechanisms of action, approved and off-label indications

Abstract: Tumor necrosis factor inhibitors (TNFi) belong to the group of biologic drugs, holding presently top positions on lists of most profitable products for pharmaceutical companies. Although current indications for TNFi include only selected diseases with an established role of immune dysfunction in their pathogenesis, studies on new indications are being carried out all over the world. The most important aspect of TNFi therapy is a targeted therapeutic approach, allowing to avoid a wide range of side effects asso… Show more

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Cited by 53 publications
(43 citation statements)
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“…The extent to which CaMKIIδ C activation in myocytes sends signals to other cells is not clear, but our studies demonstrate that the cardiomyocyte initiates signals though CaMKIIδ that lead to upregulation of TNF-α. TNF-α inhibitors such as etanercept have been used to inhibit TNF-α signaling in patients with various autoimmune disorders [39]. Effects of TNF-α inhibitors on cardiovascular disease outcomes have also been evaluated with uncertain results that could in part be due to systemic responses to sustained antibody administration [28].…”
Section: 7 Discussionmentioning
confidence: 99%
“…The extent to which CaMKIIδ C activation in myocytes sends signals to other cells is not clear, but our studies demonstrate that the cardiomyocyte initiates signals though CaMKIIδ that lead to upregulation of TNF-α. TNF-α inhibitors such as etanercept have been used to inhibit TNF-α signaling in patients with various autoimmune disorders [39]. Effects of TNF-α inhibitors on cardiovascular disease outcomes have also been evaluated with uncertain results that could in part be due to systemic responses to sustained antibody administration [28].…”
Section: 7 Discussionmentioning
confidence: 99%
“…As regards TNF inhibitors, such as adalimumab and etanercept, this discrepancy may be due to the well-known intrinsic chemical and pharmacological properties between the two agents. As reviewed by Cessak et al [36], these two biologics show to have different kinetic parameters, as well as different binding affinities and avidities. Finally, the anti p40-dependent lesser 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 12 normalization of S100A7 expression compared to adalimumab treatment, may be due to the different target molecules; in fact, ustekinumab interferes with the expansion of Th1 and Th17, acting on IL-12 and IL-23, respectively.…”
Section: Discussionmentioning
confidence: 99%
“…TNFSF cytokines can also regulate neuronal activity and drive inflammatory responses in a range of tissue structural cells, including epithelial cells and fibroblasts. These insights have led to intensive efforts to treat other inflammatory diseases through TNF neutralization, and multiple TNF-blocking agents (such as adalimumab, certolizumab pegol, etanercept, golimumab and infliximab) are now approved for diseases such as juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, spondylarthropathies, inflammatory bowel disease and uveitis 7,8 (TABLE 1). Investigations into the targeting of other TNFSF members have led to a number of clinical trials in different diseases and resulted in the successful development of belimumab, an antibody against B cell activating factor (BAFF, also known as TNFSF13B), and denosumab, an antibody targeting receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL, also known as TNFSF11), for the treatment of systemic lupus erythematosus (SLE) and osteoporosis, respectively 911 .…”
mentioning
confidence: 99%