What is the mechanism of action for Cimzia?
Cimzia (certolizumab pegol) is a tumor necrosis factor (TNF) blocker. TNF is a protein made by white blood cells that can cause inflammation in the body. Cimzia works by attaching to TNF-α and stops it from working to produce inflammatory substances such as interleukin-1 (IL-1), nitric oxide, and prostaglandins.
Research shows that TNF is involved in many inflammatory conditions, including rheumatoid arthritis, psoriasis, and Crohn's disease. By neutralizing TNF, inflammation in the body is reduced. This results in an improvement of symptoms for a variety of autoimmune conditions.
Cimzia is PEGylated, which means it is attached to polyethylene glycol. This helps the medication stay in your body longer before it is broken down.
Is Cimzia a TNF antagonist?
Yes. Cimzia is a TNF antagonist, also sometimes called a TNF blocker. It attaches to and neutralizes TNF-α, which is a substance that causes inflammation in the body. By blocking the actions of TNF, patients with various inflammatory conditions experience relief of their symptoms.
Unique Mechanism of Action: Beyond TNF-alpha Blockade
Certolizumab pegol is a PEGylated fragment of a humanized monoclonal antibody, lacking an Fc region. This lab-engineered structure allows Cimzia to bind with high affinity to both soluble and membrane-bound tumor necrosis factor alpha (TNF-α), thereby interrupting pro-inflammatory signaling that drives autoimmune diseases. Absence of the Fc region means the drug does not trigger complement-dependent or antibody-dependent cytotoxicity, unlike other TNF inhibitors such as adalimumab or infliximab. Additionally, Cimzia does not induce apoptosis in immune cells or cause neutrophil degranulation, further reducing the risk of excessive immunosuppression.
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The Impact of PEGylation: Improved Pharmacokinetics and Tissue Targeting
A defining feature of Cimzia is PEGylation—a process attaching polyethylene glycol (PEG) molecules to the antibody fragment. PEGylation prolongs certolizumab pegol's half-life to about 14 days, allowing flexible dosing intervals (every two or four weeks). Notably, PEGylation also enhances the drug’s distribution to inflamed tissues, which may contribute to efficacy in rheumatoid arthritis and Crohn’s disease.
Unlike non-PEGylated biologics, certolizumab pegol exhibits prolonged persistence in inflamed joints and undergoes renal clearance after PEG cleavage. Importantly, pegylation has also been shown to decrease uptake by dendritic cells, which may lower immunogenicity and reduce the risk of anti-drug antibody (ADA) formation.
What is Cimzia used for?
Cimzia is an anti-TNF biologic that is FDA approved to treat the following conditions:
- Crohn’s disease
- Rheumatoid arthritis
- Psoriatic arthritis
- Ankylosing spondylitis
- Polyarticular juvenile idiopathic arthritis
- Non-radiographic axial spondyloarthritis
- Psoriasis
Cimzia is given as an injection under the skin every 2 to 4 weeks.
References
- de Bourayne, M., Meunier, S., Bitoun, S., Correia, E., Mariette, X., Nozach, H., & Maillère, B. (2022). Pegylation Reduces the Uptake of Certolizumab Pegol by Dendritic Cells and Epitope Presentation to T-Cells. Frontiers in immunology, 13, 808606. https://doi.org/10.3389/fimmu.2022.808606
- Goel, N., et. al. (2010). Certolizumab pegol. In: mAbs. DOI: https://doi.org/10.4161%2Fmabs.2.2.11271
- National Cancer Institute. (n.d.). Tumor Necrosis Factor. Accessed 06/27/2024 at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/tumor-necrosis-factor
- Patel, A. M., et. al. (2014). Certolizumab pegol: a new biologic targeting rheumatoid arthritis. In: Expert Review of Clinical Pharmacology. DOI: https://doi.org/10.1586%2Feci.10.69
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Drug information
- Cimzia Information for Consumers
- Cimzia prescribing info & package insert (for Health Professionals)
- Side Effects of Cimzia (detailed)
- Cimzia user reviews (91)
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