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.

Keywords: adalimumab (ADL); anti-TNF-α agents; biosimilars; effectiveness; immunogenicity; inflammatory bowel disease; infliximab (IFX); monoclonal antibodies; safety.

Figure 1

Schematic view of nomenclature for monoclonal antibodies (MAbs) (left) and general representation of their “Y” structure (right) [6]. Note the change in color, representing the differing humanization of antibodies.

Figure 2

Factors influencing the etiology and pathophysiology of IBD [30,32,34].

Figure 3

Main cells and cytokines involved in the immune response in IBD. The red line depicts TNF-α as the main proinflammatory cytokine of the inflammatory cascade [50].

Figure 4

Monoclonal IgG1 anti-TNF-α antibodies (MAbs): infliximab, IFX (on the left), and adalimumab, ADL (on the right). IFX: (a) Human IgG1 constant region, (b) mouse antigen-binding variable region, and (c) homotrimer of TNF-α; ADL: (a) human IgG1 constant region, (b) human antigen-binding variable region, and (c) homotrimer of TNF-α [6,60].

Figure 5

Pharmacological armamentarium of IBD and paradigm shift in the management of IBD [61].