What is Adalimumab (tumor necrosis factor inhibitor)?

What is Adalimumab?

Adalimumab is a fully human recombinant IgG1 monoclonal antibody that specifically binds to and blocks tumor necrosis factor-alpha (TNF-α), preventing its interaction with cell surface TNF receptors and inducing lysis of TNF-expressing cells. 1

Molecular Structure and Formulation

• Adalimumab is produced using phage display technology, resulting in an antibody with human-derived heavy and light chain variable regions and human IgG1:κ constant regions 1
• The molecule consists of 1330 amino acids with a molecular weight of approximately 148 kilodaltons 1
• It is manufactured using recombinant DNA technology in Chinese Hamster Ovary (CHO) cells and purified through a process including viral inactivation and removal steps 1
• Adalimumab is supplied as a sterile, preservative-free, clear and colorless solution for subcutaneous administration with a pH of approximately 5.2 1

Mechanism of Action

• Adalimumab binds specifically to TNF-α and blocks its interaction with both p55 and p75 cell surface TNF receptors 1
• The drug lyses surface TNF-expressing cells in vitro when complement is present 1
• It does not bind to or inactivate lymphotoxin (TNF-β) 1
• The mechanism involves both neutralization of TNF-α bioactivity and induction of apoptosis in TNF-expressing mononuclear cells 2

Classification Among TNF Inhibitors

• Adalimumab is one of five TNF inhibitors approved since 2000, alongside infliximab, certolizumab pegol, etanercept, and golimumab 3
• Unlike infliximab (a chimeric mouse/human antibody) and etanercept (a fusion protein), adalimumab is a fully humanized anti-TNF-α monoclonal antibody that cannot be distinguished from normal human IgG1 3
• It is administered subcutaneously, distinguishing it from intravenously administered infliximab 3

FDA-Approved Indications

Adalimumab has been approved for multiple inflammatory conditions over the past two decades:

• Rheumatoid arthritis (alone or in combination with methotrexate) 3
• Psoriatic arthritis 3
• Ankylosing spondylitis 3
• Psoriasis (moderate-to-severe plaque psoriasis) 3
• Crohn's disease 3
• Ulcerative colitis (including pediatric patients 5 years and older) 3, 1
• Juvenile idiopathic arthritis 3
• Non-infectious uveitis (including pediatric patients 2 years and older) 1
• Hidradenitis suppurativa (including pediatric patients 12 years and older) 1
• Behçet's disease 3

Route of Administration and Standard Dosing

• Adalimumab is administered by subcutaneous injection 3, 1
• For psoriasis, the standard regimen is 80 mg at week 0,40 mg at week 1, then 40 mg every other week thereafter 3, 4
• The drug does not require routine laboratory monitoring, unlike traditional systemic treatments 5
• Available formulations include prefilled pens, prefilled syringes, and institutional use vials in various strengths (10 mg, 20 mg, 40 mg, and 80 mg) 1

Efficacy in Inflammatory Bowel Disease

• Among TNF inhibitors, adalimumab (along with infliximab and golimumab) can induce clinical and endoscopic remission in inflammatory bowel disease, which is not true for etanercept 3
• This distinction is clinically important when selecting TNF inhibitors for patients with concomitant inflammatory bowel disease 6

Safety Profile and Common Adverse Effects

• The most common side effects are injection site reactions, occurring in approximately 20% of patients 3, 5
• Adalimumab increases the risk of serious infections, with a two-fold increased risk reported in clinical trials 5
• The most notable infectious complication is reactivation of tuberculosis, requiring tuberculosis screening before initiation 3, 7
• Rare but serious adverse effects include worsening or initiation of congestive heart failure, lupus-like syndrome, lymphoma promotion, medically significant cytopenias, and neurological diseases including multiple sclerosis 5
• The safety profile is generally favorable compared with traditional systemic treatments and similar to other TNF antagonists 5, 8