Infliximab Overview

Introduction of Infliximab

Infliximab (trade name Remicade) is a tumor necrosis factor (TNF-alpha or TNF-α) blocker and a chimeric monoclonal IgG1 antibody composed of human constant (75%) and murine variable (25%) regions. It is produced by a recombinant cell line cultured by continuous perfusion and was developed by Junming Le and Jan Vilček at New York University School of Medicine and in collaboration with Centocor, (now Janssen Biotech, Inc.). Infliximab is an artificial antibody. It was originally developed in mice as a mouse antibody. Because humans have immune reactions to mouse proteins, the mouse common domains were replaced with similar human antibody domains. Infliximab was first approved by the FDA in 1998 under the market name Remicade as an intravenous injection. It is indicated for the treatment of various inflammatory disorders such as adult or pediatric Chron's disease, adult or pediatric ulcerative colitis, rheumatoid arthritis in combination with methotrexate, ankylosing spondyliti, psoriatic arthritis, and plaque psoriasis. In clinical trials, multiple infusions of infliximab displayed in a reduction of signs and symptoms of inflammatory diseases and induction of remission in patients who have had an inadequate response to alternative first-line therapies for that disorder. There are currently two biosimilars of infliximab available in the US market that demonstrate a high degree of similarity to the reference product, Remicade. They are approved for all eligible indications of the reference product. Inflectra, a first biosimilar drug product, was approved in 2016. In December 2017, Ixifi, a second biosimilar that was developed by Pfizer, was granted approval by the FDA.

Mechanism of Action of Infliximab

Crohn's disease is a lifelong inflammatory disorder characterized by the presence of inflammatory ulcerative lesions in the gastrointestinal tract. Lesions most commonly involve the large and small bowel, giving rise to symptoms of abdominal pain, weight loss, gastrointestinal haemorrhage, and fistula formation. Lesions most commonly involve the large and small bowel, giving rise to symptoms of abdominal pain, weight loss, gastrointestinal haemorrhage, and fistula formation. To date, treatment has been geared towards symptomatic relief of disease exacerbations via pharmacological interventions such as aminosalicylates, corticosteroids, immunosuppressive agents, antibiotics, and nutritional therapy. Surgery is indicated in those patients who have failed to respond to medical management, or to correct intestinal obstruction or abscesses. Surgical intervention is by no means curative, with inflammatory episodes recurring in ⩾80% of patients after intestinal resection. The inflammatory response in Crohn's disease is regulated by intercellular mediators known as cytokines. The major contributing factor to chronic local inflammation in Crohn's disease is local mucosal overproduction of proinflammatory cytokines to anti-inflammatory cytokines. Tumour necrosis factor-α (TNF-α) is one of several proinflammatory mediators, which has a central role in chronic inflammatory conditions, such as Crohn's disease, rheumatoid arthritis, and other granulomatous diseases. Its hyperactivity and enhanced signaling pathways can be observed in inflammatory diseases where it activates further pro-inflammatory cascades. Infliximab is a chimeric monoclonal antibody to TNF-α, developed as a therapeutic agent for TNF-α mediated diseases. Infliximab neutralizes the biological activity of TNF-α by binding with high affinity to the soluble (free floating in the blood) and transmembrane (located on the outer membranes of T cells and similar immune cells) forms of TNF-α and inhibits or prevents the effective binding of TNF-α with its receptors. By binding to both the soluble subunit and the membrane-bound precursor of TNF-α, infliximab disrupts the interaction of TNF-α with its receptors and may also cause lysis of cells that produce TNF-α.

Fig 1. Mechanism of Action of Infliximab

Table 1. Clinical Projects of Infliximab*

Table 2. Approved Drugs of Infliximab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Remicade	Crohn’s Disease, Pediatric Crohn’s Disease, Ulcerative Colitis, Pediatric Ulcerative Colitis, Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Plaque Psoriasis	Lyophilized concentrate for injection	100MG / vial	Intravenous infusion	Centocor Inc	August 24, 1998
Remicade	Gastroentology-Hepatology	Powder for concentrate for solution for infusion	100MG / vial	Intravenous infusion	Centocor B.V.	September 16, 2010
Remicade	Inflammatory, Antirheumatic	Lyophilized concentrate for injection	100MG / vial	Intravenous infusion	Janssen Biotech	May, 2002

What We Provide

Therapeutic Antibody

Infliximab

We provide high-quality Infliximab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
*The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Infliximab

**Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103772

For research use only. Not intended for any clinical use.