Under the Umbrella of Clinical Pharmacology: Inflammatory Bowel Disease, Infliximab and Adalimumab, and a Bridge to an Era of Biosimilars

Abstract

Monoclonal antibodies (MAbs) have revolutionized the treatment of many chronic inflammatory diseases, including inflammatory bowel disease (IBD). IBD is a term that comprises two quite similar, yet distinctive, disorders—Crohn’s disease (CD) and ulcerative colitis (UC). Two blockbuster MAbs, infliximab (IFX) and adalimumab (ADL), transformed the pharmacological approach of treating CD and UC. However, due to the complex interplay of pharmacology and immunology, MAbs face challenges related to their immunogenicity, effectiveness, and safety. To ease the burden of IBD and other severe diseases, biosimilars have emerged as a cost-effective alternative to an originator product. According to the current knowledge, biosimilars of IFX and ADL in IBD patients are shown to be as safe and effective as their originators. The future of biosimilars, in general, is promising due to the potential of making the health care system more sustainable. However, their use is accompanied by misconceptions regarding their effectiveness and safety, as well as by controversy regarding their interchangeability. Hence, until a scientific consensus is achieved, scientific data on the long-term effectiveness and safety of biosimilars are needed.

TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice

“…S2A . As infliximab has been used successfully in the treatment of inflammatory bowel disease (IBD) [ 32 ] and the development of MASLD has been associated with impairments of intestinal barrier function [ 33 ], we next determined levels of endotoxin in portal plasma being indicative of intestinal barrier dysfunction. Bacterial endotoxin levels were significantly higher in both SFC-fed groups compared to C-fed mice ( Table 1 ).…”

Clinical Pharmacology of Vinpocetine: Properties Revisited and Introduction of a Population Pharmacokinetic Model for Its Metabolite, Apovincaminic Acid (AVA)

“…Namely, evidence shows that vinpocetine can inhibit the activation of proinflammatory mediators mediated via the tumor necrosis factor alpha (TNF-α) signaling pathway in various cell types, including macrophages, endothelial cells, and vascular smooth cells. As TNF-α is the main pharmacological target in many diseases, such as inflammatory bowel disease (Crohn's disease and ulcerative colitis) [49], these findings should be further researched and tested in disease models that have inflammation in etiopathogenesis. For instance, in a mouse model of acetic acid-induced colitis, the administration of 30 mg/kg of vinpocetine demonstrated multifaceted properties, including anti-inflammatory, antioxidant, and analgesic effects.…”

Super Carbonate Apatite-miR-497a-5p Complex Is a Promising Therapeutic Option against Inflammatory Bowel Disease

“…A part of mononuclear cells turns into macrophages which produce a large number of inflammatory cytokines such as IL-23, TNF-α, and IL-6 by stimulation of intestinal bacteria, leading to chronic inflammation [23][24][25]. Co-culture of macrophages and intestinal epithelial cells is also used as a colitis model in vitro [68]. Therefore, we examined whether miR-497a-5p would suppress the production of inflammatory cytokines TNF-a, IL-6, and IL-12p40 (a subunit of IL-23), when lipopolysaccharides (LPS) at 100 ng/mL was added to mouse macrophage cell line J774a.1 according to the time schedule shown in Figure 5A.…”