Golimumab (brand name Simponi) is a human IgG1 monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. It is a full-size antibody with a molecular mass of approximately 150 kilodaltons that exhibits multiple glycoforms. The drug binds and inhibits soluble and transmembrane human TNFα. The product was originally isolated from a hybridoma clone produced by HuMab (Medarex) transgenic mice that had been immunized with human TNFα. The golimumab-secreting clone was selected after being assayed for human light and heavy chains, and for TNFα-binding. The commercial product is produced in a recombinant cell line cultured by continuous perfusion. Golimumab was approved in the US and Canada in April 2009 as a treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. The product was developed by Centocor and Janssen Pharmaceutical KK, in collaboration with Schering-Plough and Mitsubishi Tanabe Pharma. Large, double-blind randomized controlled trials in patients with rheumatoid arthritis have shown that golimumab in combination with methotrexate was more effective than methotrexate alone. When clinically indicated, golimumab is estimated as a moderate cost-effective treatment option. National Institutes for Health and Care Excellence (NICE) stated that treatment with golimumab is not recommended for RA patients who have failed prior TNFi treatment. Unlike other TNFi treatments such as certolizumab pegol, there have been no reported cases of drug-induced lupus-like syndrome (DILS).
Autoimmune inflammatory diseases affect approximately 7.6-9.4% of the world population, especially among the young and middle-aged women. Frequently accompanied by severe and chronic morbidity, autoimmune diseases are also leading causes of death all around world. Excessive and prolonged activation of immune cells, such as T and B lymphocytes, and overexpression of the master pro-inflammatory cytokine tumor necrosis factor alpha (TNF), together with other mediators play a central role in the pathogenesis of autoimmune inflammatory responses in rheumatoid arthritis inflammatory bowel disease, Crohn’s disease, and ankylosing spondylitis. Tumor necrosis factor (TNF), a pleiotropic cytokine mainly produced by activated macrophages, modulates a wide range of biological functions in multiple tissues and organs. Besides its effects on tumor cell death, TNF is a key mediator of both acute and chronic inflammation that serves a key role in the pathogenesis of a variety of immunological diseases. As majority of TNF-α blockers, Golimumab inhibits soluble and transmembrane forms of TNF-α binding to their specific receptors and blocking in consequence their bioactivity. Furthermore, Golimumab neither bind nor inhibit other members of TNF-α such as the lymphotoxin (TNF-β) Competing with TNF-α receptors, Golimumab regulates TNF-α pro-inflammatory cytokines essentially produced by activated macrophages. Golimumab has also the power to fix complement inducing cell lysis and to participate in immune responses implicating antibody-dependent cell cytotoxicity function. Following Golimumab therapy, numerous positive responses related to RA disease cure were obtained, such as reductions in levels of C-reactive protein (CRP), IL-6, MMP-3, ICAM-1, and VEGF.
Fig 1. Mechanism of Action of Golimumab
Table 1. Clinical Projects of Golimumab*
Table 2. Approved Drugs of Golimumab**
|INN (trade name)||Therapeutic area||Dose||Strength||Route||Company||Marketing start||Market|
|Simponi||Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Ulcerative Colitis||Concentrate for injection||50MG||Subcutaneous injection||Centocor Ortho Biotech||April 24, 2019|
|Simponi||Active rheumatoid arthritis, Active and progressive psoriatic arthritis, Axial spondyloarthritis, Moderately to severely active ulcerative colitis, Polyarticular juvenile idiopathic arthritis||Solution for injection||50MG||Subcutaneous injection||Janssen Biologics||October 1, 2009|
*The table was excerpted from the following website
**Information presented in the table were collected from the following website:
For research use only. Not intended for any clinical use.