The FDA first approved the original molecule of adalimumab for the treatment of rheumatoid arthritis. It was the third tumor necrosis factor (TNF) alpha inhibitor to be approved by the FDA after infliximab and etanercept. Subsequently, the FDA has approved adalimumab for the following indications:
The off label uses of adalimumab include:
Several biosimilar molecules have now been developed, for, eg. ABP 501, BI 695501, and SB5.
Adalimumab is a fully human, high-affinity, recombinant immunoglobulin G (IgG) anti-TNF alpha monoclonal antibody. It is a molecule comprising 1330 amino acids and has a molecular weight of approximately 148 kDa. It inhibits the binding of TNF alpha (both soluble and membrane-bound). It inhibits its interaction with p55 (TNFR1) and p75 (TNFR2) cell surface TNF receptors, which in turn interferes with cytokine-driven inflammatory processes. It is identical in structure and function to the naturally occurring human IgG1, and thus has high selectivity for TNF alpha, and has low immunogenic potential.
It does not affect or bind to other cytokines like lymphotoxin or interleukins. Its efficacy in various arthritis owes to its potent osteogenic action. TNF mediates activation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) ligand (RANKL) receptors on stromal or osteoblast cells. TNF blockade thus inhibits subsequent destruction of cartilage and bone. TNF also plays a role in osteoclast maturation and activation, which remains in check with TNF blockade. Anti-TNF agents also downregulate serum matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3). All of these factors contribute to the efficacy of TNF inhibitors in arthritis.
Administer injection subcutaneously at separate sites in the thigh or lower abdomen (avoid areas within 2 inches of the navel); rotate injection sites; may leave at room temperature for 15 to 20 minutes prior to use; do not remove cap or cover while allowing the product to reach room temperature; not for administration to the skin which is red, tender, bruised, hard, or that scars, stretch marks, or psoriasis plaques.
The recommended doses for each indication are:
The injection is available as a pre-filled glass syringe or pen, or as a single-use glass vial in doses of 10 mg, 20 mg, 40 mg or 80 mg. Patients may use the adalimumab pen as self-administration. The vial is for institutional use only.
Following a single 40 mg subcutaneous dose, the pharmacokinetics of adalimumab are as follows:
The most common adverse effects of adalimumab are:
Although the manufacturers have listed no contraindications, adalimumab has not been adequately studied in patients who are younger than four years of age and weighing less than 15 kg. CLinicians should avoid using it in this age group as a precautionary measure.
Clinicians must also avoid adalimumab in cases of hypersensitivity, patients with underlying foci of infection, congestive cardiac failure, or hepatic dysfunction.
Concomitant administration of live vaccines is contraindicated. Also, the risk of serious infections increases significantly in the co-administration of abatacept and anakinra.
Long term human or animal studies on adalimumab have not been conducted, leaving the toxicity profile mostly unknown. It has not demonstrated to be mutagenic in vitro or in vivo studies.
The FDA categorizes adalimumab as a pregnancy category B drug. There is no conclusive published evidence of poor pregnancy outcomes or specific pattern of defects in infants exposed prenatally to adalimumab.
The administration of TNF alpha antagonists such as adalimumab requires thorough knowledge and working experience with these drugs. A few points to be kept in mind are:
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