Adalimumab Overview

Introduction of Adalimumab

Adalimumab (trade name Humira) is a a recombinant, fully human IgG1 monoclonal antibody and subcutaneously administered biological disease modifier which targets tumor necrosis factor (TNF). The drug is produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific viral inactivation and removal steps. Adalimumab is used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis, hidradenitis suppurativa, juvenile idiopathic arthritis, and uveitis. It was originally launched by Abbvie in the US and approved in 2002 by the FDA. This drug is available in a prefilled syringe form and convenient pen form for subcutaneous self-administered doses. Adalimumab-adaz (Hyrimoz) is a new biosimilar to adalimumab developed by Novartis AG. It was approved by the FDA on October 31, 2008. However, due to the importance of TNF in host defense, one of the issues of major concern with all TNF-blockers, including adalimumab, is the increased risk of infections and malignancies.

Mechanism of Action of Adalimumab

Psoriasis is a chronic inflammatory immune-mediated skin disease that affects 1%-3% of general population. The disease is characterized by hyperproliferation and abnormal differentiation of keratinocytes, vascular changes in the papillary dermis, intraepidermal accumulation of neutrophils and dermal inflammation with prominent lymphocytic infiltrate. The development of psoriasis has a multifactorial nature resulting from the interaction between genetic predisposition and environmental factors. Pathogenic mechanisms are considered to be secondary to an abnormal immune response, with an aberrant regulation of both the adaptative (CD4+ Th1 lymphocytes and CD8+ type-1 T-cells) and the innate immunity (dendritic cells, macrophages, keratinocytes) resulting in a complex network of cytokines, chemokines and growth factors. The serendipitous discovery of the effectiveness of anti-TNF biologics in psoriasis has suggested the crucial role of this cytokine, which can be implicated in multiple events of psoriasis-related inflammation: attraction of leucocytes into the skin, activation of dendritic cells and T lymphocytes, release of epithelial and vascular growth factors, synthesis of cytokines, chemokines and other proinflammatory mediators via activation of NF-kappaB. The mechanism of action of adalimumab is primarily linked to the neutralization of TNF-alpha bioactivity by preventing the interaction of TNF-alpha with the cell surface TNF receptors. Through this mechanism, adalimumab inhibits several TNF-alpha-induced events, i.e., the release of serum cytokines (IL-6), acute phase reactants of inflammation, matrix metalloproteases and other markers of cartilage and synovium turnover, and the expression of adhesion molecules responsible for leukocyte migration. In addition, adalimumab lyses TNF-expressing cells in the presence of complement.

Fig 1. Mechanism of Action of Adalimumab

Table 1. Clinical Projects of Adalimumab*

Table 2. Approved Drugs of Adalimumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Humira	Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Adult Crohn’s Disease, Pediatric Crohn’s Disease, Ulcerative Colitis, Plaque Psoriasis, Hidradenitis Suppurativa, Uveitis	Solution for injection	40MG/0.8ML	Syringe	AbbVie	December 31, 2002
Humira	plaque psoriasis, rheumatoid arthritis, axial spondyloarthritis , Crohn’s disease, ulcerative colitis, polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis, hidradenitis suppurativa, non-infectious uveitis	Solution for injection	40MG/0.8ML	Syringe	AbbVie	September 8, 2003

What We Provide

Therapeutic Antibody

We provide high-quality 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=Adalimumab

**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=125057