Certolizumab pegol
Certolizumab pegol Uses, Dosage, Side Effects, Food Interaction and all others data.
Certolizumab pegol is a pegylated monoclonal antibody against the tumor necrosis factor-alpha (TNF-alpha). It is formed with a humanized Fab fragment of 50 kDa, from an IgG 1 isotype, fused to a 40 kDa polyethylene glycol moiety replacing the Fc antibody region. The absence of the Fc region was ideated to prevent complement fixation and antibody-mediated cytotoxicity as well as to markedly increase its half-life.
Certolizumab does not require glycosylation for active function and hence, its production is significantly more affordable when compared to other existing TNF-alpha therapies as it can be done directly in bacterial hosts such as E. coli. It was developed and manufactured by UCB Pharma, first FDA approved in 2008 and updated for a new indication on March 28, 2019.
As part of the mechanism of action and nature of the drug, certolizumab does not induce apoptosis in cultured lymphocytes and monocytes. However, as a piece of the inhibition of inflammation, certolizumab pegol inhibits lipopolysaccharide-induced production of IL-1 beta and it induces nonapoptotic cell death via signaling transmembrane TNF-alpha.
| Trade Name | Certolizumab pegol |
| Generic | Certolizumab pegol |
| Certolizumab pegol Other Names | Certolizumab pegol |
| Type | |
| Formula | C2115H3252N556O673S16 |
| Weight | 91000.0 Da (Pegylated) |
| Protein binding | Monoclonal antibodies are usually not required to have protein binding studies. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Certolizumab pegol is a tumor necrosis factor (TNF) blocker used to treat a variety of autoimmune and autoinflammatory conditions like Crohn's disease, rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, axial spondyloarthritis, and plaque psoriasis.
Certolizumab pegol has been approved for several different conditions listed below:
- Symptomatic management of Chron's disease patients and for the maintenance of clinical response in patients with moderate to severe disease with inadequate response to conventional therapy.
- Treatment of adult patients with moderate to severely active rheumatoid arthritis.
- Treatment of adult patients with active psoriatic arthritis.
- Treatment of adult patients with active ankylosing spondylitis.
- Treatment of adult patients with moderate-to-severe plaque psoriasis that are candidates for systemic therapy or phototherapy.
- Treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation.
In Canada, certolizumab pegol is additionally approved in combination with methotrexate for the symptomatic treatment, including major clinical response, and for the reduction of joint damage in adult patients with moderately to severely active rheumatoid arthritis and psoriatic arthritis.
Inflammation is a biological response against a potential threat. This response can be normal but in certain conditions, the immune system can attack the body's normal cells or tissues which causes an abnormal inflammation. TNF-alpha has been identified as a key regulator of the inflammatory response. The signaling cascades of this inflammatory mediator can produce a wide range of reactions including cell death, survival, differentiation, proliferation and migration.
Certolizumab pegol is also used to associated treatment for these conditions: Active Ankylosing Spondylitis or Non-Radiographic Axial Spondyloarthritis, Moderate-to-severe Plaque Psoriasis, Moderately to Severely Active Rheumatoid Arthritis, Psoriatic Arthritis, Psoriatic arthritis aggravated, Severe Crohn's Disease, Active Ankylosing spondylitis, Moderate Crohn's disease, Moderate Rheumatoid arthritis, Severe Rheumatoid arthritis
How Certolizumab pegol works
Certolizumab targets the activation of TNF-alpha with high affinity (KD 90 pM and IC90 0.004 mcg/ml) which in order, inhibits the downstream inflammatory process. It acts by binding and neutralizing the soluble and membrane portions of TNF-alpha without inducing complement or antibody-dependent cytotoxicity due to the lack of the Fc region. The inhibition of TNF-alpha is achieved in a dose-dependent manner and it does not present activity against lymphotoxin alpha (TNF-beta).
One additional feature od certolizumab pegol is that, due to the presence of the PEGylation, it is more significantly distributed into inflamed tissues when compared to other TNF-alpha inhibitors such as infliximab and adalimumab.
Toxicity
The oral ld50 observed in mice is determined to be of 300 mg/kg. To this date, there have not been reports of overdosage, however, in case of accidental overexposure close monitoring is recommended.
Certolizumab pegol does not present mutagenic potential nor presents effects in fertility and reproductive performance. On the other hand, carcinogenicity studies have not been performed.
Volume of Distribution
Certolizumab pegol volume of distribution is reported to be in the range of 4-8 L. It is known to have a very good distribution in the joints when compared to other TNF-alpha inhibitors.
Elimination Route
After subcutaneous administration, the peak plasma concentration is reached between 54 and 171 hours with a bioavailability of 80%. Certolizumab presents a linear pharmacokinetic profile with a peak plasma concentration of 43-49 mcg/ml.
Half Life
The circulatory half-life of certolizumab is of 14 days.
Clearance
The clearance rate of certolizumab pegol ranged between 9-14 ml/h when administered intravenously. However, when administered subcutaneously, the clearance rate is estimated to range between 14-21 ml/h depending on the patient condition.
Elimination Route
As certolizumab is a monoclonal antibody, the elimination route is not widely studied. However, it is known that the elimination of the PEG moiety is dependent on the renal function which links it directly with a high portion of renal elimination.
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