Certolizumab pegol

Drug Reference 9 min 340

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Created On: 09/01/2020

Certolizumab pegol is a recombinant, polyethylene glycolylated monoclonal antibody. It is the fourth monoclonal antibody which has been approved by USFDA and EMA for rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, active psoriatic arthritis.

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Introduction

Certolizumab pegol is a recombinant, polyethylene glycolylated monoclonal antibody. It exerts its pharmacological effects by neutralizing membrane-associated and soluble human TNFα but acts differently when compared to infliximab and adalimumab which is due to its different structure. The studies prove that this TNFα inhibitor can be an efficient monotherapy regimen, i.e. without methotrexate. Certolizumab pegol is the fourth monoclonal antibody which has been approved by USFDA and EMA for rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, active psoriatic arthritis.

Pharmacological class: Protein-Based Monoclonal Antibody

Indications

Moderate to severely active rheumatoid arthritis
Active psoriatic arthritis
Active ankylosing spondylitis
Crohn’s disease

Pharmachologic action

The Certolizumab pegol acts by binding to human TNFα which is a pro-inflammatory cytokine and triggers inflammation. It selectively neutralizes membrane-associated and soluble human TNFα and this effect is dose-dependent in nature. It does not show cross-reactivity to the normal human tissues.

Dosage

Usual Adult Dose for Crohn’s Disease

Initial dose: 400 mg initially and at weeks 2 and 4,

Maintenance dose: If response occurs, follow with 400 mg every four weeks

Usual Adult Dose for Rheumatoid Arthritis

Initial dose: 400 mg initially and at weeks 2 and 4, followed by 200 mg every other week

Maintenance dose: 400 mg every four weeks

Usual Adult Dose for Psoriatic Arthritis

Initial dose: 400 mg initially and at week 2 and 4, followed by 200 mg every other week

Maintenance dose: 400 mg every four weeks

Usual Adult Dose for Ankylosing Spondylitis

Initial dose: 400 mg (given as two subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every week or 400 mg every 4 weeks

Note: Certolizumab pegol is administered by subcutaneous injection.

Pharmacokinetics

Absorption: The bioavailability is approximately 80%, and the peak plasma concentration reaches between 54 and 171 hours after subcutaneous administration. It has a linear pharmacokinetic profile, exhibiting the peak plasma concentration of 43-49 mcg/mL

Volume of distribution (Vd): The Vd of Certolizumab pegol has been reported to be in the range of 4-8 L. It shows a perfect distribution in the joints when compared to other TNF-alpha inhibitors

Protein binding: It does not have any protein binding studies

Metabolism: It contains a polyethene glycol (PEG) group; therefore, its metabolism and elimination are delayed. After metabolization, the polyethylene glycol group gets separated from the parent molecule. In this way, the antibody portion rescues the degradation and went into the cells for action. The reticuloendothelial system degrades it into peptides and amino acids which can be further used for de-novo protein synthesis. PEG is processed to carboxylic acid by the action of enzyme alcohol dehydrogenase

Route of elimination: The elimination route of certolizumab is not widely studied; however the removal of the PEG moiety is dependent on the renal function

Half-life: It has a circulatory half-life of 14 days

Clearance: The clearance rate of certolizumab pegol ranged between 9-14 ml/h and 14-21 ml/h when administered intravenously and subcutaneously, respectively. The clearance rates are also dependent on the condition of the patient

Contraindications

No contraindications are reported for certolizumab pegol

Drug interaction

The use of certolizumab pegol with Biological DMARDs is not recommended as it can lead to increased risk of serious infections
The concurrent use of certolizumab pegol with other live and attenuated vaccines should be avoided
It can interfere with certain coagulation assays such as activated partial thromboplastin time (aPTT) tests

Side effects

Common side effects are:

Upper respiratory tract infection
Urinary tract infection
Skin rash

Precautions

The use of certolizumab pegol should not be started during an active infection. If any severe life-threatening infections occur, use should be terminated
Consider the use of empiric antifungal therapy along with certolizumab pegol for those who reside or travel to regions where mycoses are endemic
The use of certolizumab pegol should be terminated if it leads to worsening of heart failure, anaphylaxis or severe allergic reactions, demyelinating disease, lupus-like syndrome, cytopenias, pancytopenia and cases of lymphoma and other malignancies
Hepatitis B virus reactivation test for HBV infection should be done before starting certolizumab pegol. The carriers of HBV should be monitored during, and several months of therapy. The use of certolizumab pegol should be stopped, if reactivation occurs, and antiviral treatment should be started

Clinical evidence

A pooled analysis was conducted by Jeffrey R Curtis et al. to evaluate the long term safety of certolizumab pegol (CZP) across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn’s disease (CD). As per the largest data available from December 1998–August 2017, the 49 UCB-sponsored clinical trials of CZP from study sites worldwide were pooled to evaluate the safety of the CZP. These trials included five PSO, one PsA, 27 RA, 15 CD and one axSpA. Serious adverse effects such as malignancies, infections, hypersensitivity events, major adverse cardiovascular events, psoriasis events, gastrointestinal perforations, and deaths were reviewed using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) were presented as per the indication. WHO/GLOBOCAN/SEER databases were used to calculate the standardised mortality and fatality rates. Effects of CZP on the pregnant women was also studied and reported. Infections were the most common adverse effects among the studied population.

Serious adverse event (SAE)	Incidence Rate (IR)
Malignancies	0.82/100 PY
Lymphoma	0.06/100 PY
GI perforation	0.08/100 PY
Cardiovascular events	0.47/100 PY

SAEs were the highest in RA and CD, respectively. Patients with psoriasis showed the lowest serious adverse events (SAE). As per this large review, the certolizumab pegol proved to have a remarkable safety profile in all the global clinical trials. This monoclonal antibody is effective for the management of axial spondyloarthritis, Crohn's disease, rheumatoid arthritis, and psoriatic arthritis. Though some indication-specific differences in certain SAE rates were observed there were no new safety signals or relevant non-disease-related laboratory abnormalities.