Abstract
The etiology of inflammatory bowel disease (IBD), of which ulcerative colitis (UC) and Crohn’s disease (CD) are the two most prevailing entities, is unknown. However, IBD is characterized by an imbalanced synthesis of pro-inflammatory mediators of the inflamed intestine, and for more than a decade tumor necrosis factor-(TNF) α has been a major target for monoclonal antibody therapy. However, TNF inhibitors are not useful for one third of all patients (i.e. “primary failures”), and further one third lose effect over time (“secondary failures”). Therefore, other strategies have in later years been developed including monoclonal antibodies targeting the interleukin (IL)-6 family of receptors (the p40 subunit of IL-12/IL-23) as well as monoclonal antibodies inhibiting adhesion molecules (the α4β7 heterodimers), which direct leukocytes to the intestinal mucosa. Recently, small molecules, which are inhibitors of Janus kinases (JAKs), hold promise with a tolerable safety profile and efficacy in UC, and the field of nanomedicine is emerging with siRNAs loaded into polyactide nanoparticles that may silence gene transcripts at sites of intestinal inflammation. Thus, drug development for IBD holds great promise, and patients as well as their treating physicians can be hopeful for the future.
Highlights
The etiology of inflammatory bowel disease (IBD), of which ulcerative colitis (UC) and Crohn’s disease (CD) are the two most prevailing entities, is unknown
Conventional management of IBD follow a step-up strategy [6, 7], and for several years the treatment options were glucocorticoids, immunomodulators [i.e. thiopurines and methotrexate], cyclosporine, 5-aminosalicylic acid, and antibiotics [8, 9], but in later years there has been a landmark of discoveries and advancements in our understanding of the innate and adaptive immune responses
One of the drawbacks attributed to biologics is, the loss of response caused by antibody formation and the costs associated with long-term therapy [12]
Summary
TNF INHIBITORS For one and a half decade, the treatment of more than 1.3 million patients with tumor necrosis factor (TNF-α) inhibitors have generated huge amounts of safety and long-term efficacy data. This class include monoclonal antibodies of which infliximab was first on the market, followed by adalimumab, certolizumab pegol (a Fab fragment), and recently golimumab (Table 1) [11].
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