Identification

Name
Certolizumab pegol
Accession Number
DB08904
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb) / Fusion proteins
Description

Certolizumab pegol is a recombinant Fab' antibody fragment against tumor necrosis factor alpha which is conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). Polyethylene glycol helps to delay the metabolism and elimination of the drugs. Chemically, the light chain is made up of 214 amino acid residues while the heavy chain is composed of 229 amino acid residues. The molecular mass of the Fab' antibody fragment itself is 47.8 kDa. It is used for the treatment of rheumatoid arthritis and Crohn’s disease. FDA approved on April 22, 2008

Protein chemical formula
C2115H3252N556O673S16
Protein average weight
91000.0 Da
Sequences
>Amino acid sequence of the light chain
DIQMTQSPSSLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASFLYSGVPY
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYPLTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Amino acid sequence of the heavy chain
EVQLVESGGGLVQPGGSLRLSCAASGYVFTDYGMNWVRQAPGKGLEWMGWINTYIGEPIY
ADSVKGRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCARGYRSYAMDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA
Download FASTA Format
Synonyms
  • CDP870
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaInjection, solution200 mg/mLSubcutaneousUcb Inc2009-05-14Not applicableUs
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaSolution200 mgSubcutaneousUcb Inc2009-08-31Not applicableCanada
CimziaSolution200 mgSubcutaneousUcb Inc2017-08-04Not applicableCanada
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaKitUcb Inc2008-04-20Not applicableUs
Categories
UNII
UMD07X179E
CAS number
428863-50-7

Pharmacology

Indication

Reducing signs and symptoms of Crohn's disease and treatment of moderately to severely active rheumatoid arthritis (RA).

Structured Indications
Pharmacodynamics

TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Biological activity associated to TNFα include the upregulation of cellular adhesion molecules and chemokines, upregulation of major histocompatibility complex (MHC) class I and class II molecules, and direct leukocyte activation. TNFα stimulates the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide. After treatment with certolizumab pegol, patients with Crohn's disease demonstrated a decrease in the levels of C-reactive protein (CRP).

Mechanism of action

Certolizumab pegol binds to free and membrane-bound human TNFα with a KD of 90pM and neutralizes its activity. Extent of neutralization is also dose-dependent. It also inhibited the release of lipopolysaccharide-induced IL-1β from monocytes. TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes in which elevated levels have been observed in patients with RA and Crohn's. Certolizumab pegol selectively neutralizes TNFα (IC90 of 4 ng/mL for inhibition of human TNFα in the in vitro L929 murine fibrosarcoma cytotoxicity assay). It does not bind to TNF-β. As certolizumab is only a Fab' fragment and thus missing the Fc region, it does not fix complement or cause antibody-dependent cell-mediated cytotoxicity. Furthermore, apoptosis of monocytes or lymphocytes, or neutrophil degranulation have not been observed in vitro.

TargetActionsOrganism
ATumor necrosis factor
neutralizer
Human
Absorption

There is a linear relationship between dose administered and Cmax and AUC. A mean Cmax of approximately 43 to 49 mcg/mL occurred at Week 5 during the initial loading dose period using the recommended dose regimen for the treatment of patients with rheumatoid arthritis (400 mg sc at Weeks 0, 2 and 4 followed by 200 mg every other week). Tmax, SubQ dose = 54 - 171 hours; Bioavailability, SubQ dose = 80% (range of 76% - 88%)

Volume of distribution

Vd, steady state, Crohn's and RA patients = 6 - 8 L

Protein binding
Not Available
Metabolism

Metabolism has not been studied in humans.

Route of elimination

The route of elimination of certolizumab pegol has not been studied in human subjects. Studies in animals indicate that the major route of elimination of the PEG component is via urinary excretion.

Half life

Terminal plasma elimation half-life = 14 days (for all doses);

Clearance

IV dose, healthy subjects = 9.21 mL/h to 14.38 mL/h; SC dose, Crohn's disease patients = 17 mL/h; SC dose, RA patients = 21.0 mL/h;

Toxicity

The most common adverse reactions (incidence ≥7% and higher than placebo): upper respiratory tract infection, rash, and urinary tract infection.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbataceptThe risk or severity of infection can be increased when Certolizumab pegol is combined with Abatacept.Approved
AdalimumabAdalimumab may increase the immunosuppressive activities of Certolizumab pegol.Approved
AfelimomabAfelimomab may increase the immunosuppressive activities of Certolizumab pegol.Investigational
AnakinraThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Anakinra.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Certolizumab pegol.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Belimumab.Approved
CanakinumabThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Canakinumab.Approved, Investigational
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Certolizumab pegol.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Certolizumab pegol.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Certolizumab pegol.Approved
EtanerceptEtanercept may increase the immunosuppressive activities of Certolizumab pegol.Approved, Investigational
FingolimodCertolizumab pegol may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Certolizumab pegol.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Certolizumab pegol.Investigational
GolimumabGolimumab may increase the immunosuppressive activities of Certolizumab pegol.Approved
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Certolizumab pegol.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Certolizumab pegol.Approved, Withdrawn
InfliximabInfliximab may increase the immunosuppressive activities of Certolizumab pegol.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Certolizumab pegol.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Certolizumab pegol.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Natalizumab.Approved, Investigational
PegloticaseThe therapeutic efficacy of Certolizumab pegol can be decreased when used in combination with Pegloticase.Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Certolizumab pegol.Approved, Investigational
PirfenidonePirfenidone may increase the immunosuppressive activities of Certolizumab pegol.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Certolizumab pegol.Approved
RilonaceptThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Rilonacept.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Certolizumab pegol.Investigational
RituximabRituximab may increase the immunosuppressive activities of Certolizumab pegol.Approved
RoflumilastRoflumilast may increase the immunosuppressive activities of Certolizumab pegol.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Certolizumab pegol.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Certolizumab pegol.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Certolizumab pegol.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Certolizumab pegol.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Certolizumab pegol.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Certolizumab pegol.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Certolizumab pegol.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Certolizumab pegol.Investigational
TocilizumabTocilizumab may increase the immunosuppressive activities of Certolizumab pegol.Approved
TofacitinibThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Certolizumab pegol.Approved, Investigational
VedolizumabThe risk or severity of infection can be increased when Certolizumab pegol is combined with Vedolizumab.Approved
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Certolizumab pegol.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Certolizumab pegol.Approved
Food Interactions
Not Available

References

General References
  1. Chimenti MS, Saraceno R, Chiricozzi A, Giunta A, Chimenti S, Perricone R: Profile of certolizumab and its potential in the treatment of psoriatic arthritis. Drug Des Devel Ther. 2013 Apr 15;7:339-48. doi: 10.2147/DDDT.S31658. Print 2013. [PubMed:23620660]
  2. Ferrante M, Vermeire S, Rutgeerts P: Certolizumab pegol in the treatment of Crohn's disease. Expert Opin Biol Ther. 2013 Apr;13(4):595-605. doi: 10.1517/14712598.2013.777039. Epub 2013 Mar 4. [PubMed:23451881]
  3. Link [Link]
External Links
KEGG Drug
D03441
PubChem Substance
347910385
ChEMBL
CHEMBL1201831
PharmGKB
PA165107055
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Certolizumab_pegol
ATC Codes
L04AB05 — Certolizumab pegol
AHFS Codes
  • 92:36.00 — Disease-modifying Antirheumatic Agents
  • 56:92.00 — Miscellaneous GI Drugs
FDA label
Download (595 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableSperm Quality1
1CompletedBasic ScienceBioavailability Study on Healthy Volunteers1
1CompletedOtherAnkylosing Spondylitis (AS) / Axial Spondyloarthritis (AxSpA) / Crohn's Disease (CD) / Non-radiographic Evidence-AxSpA / Psoriatic Arthritis / Rheumatoid Arthritis2
1CompletedTreatmentHealthy Volunteers2
1RecruitingTreatmentStage IV Lung Adenocarcinoma1
2Active Not RecruitingTreatmentCrohn's Disease (CD)1
2CompletedTreatmentChronic Plaque Psoriasis1
2CompletedTreatmentCrohn's Disease (CD)3
2CompletedTreatmentPsoriasis1
2CompletedTreatmentRheumatoid Arthritis1
2RecruitingPreventionAntiphospholipid Syndrome in Pregnancy / Complications, Pregnancy / High Risk Pregnancies / Lupus Anticoagulant Disorder1
2RecruitingTreatmentAnkylosing Spondylitis (AS)1
2RecruitingTreatmentRheumatoid Arthritis1
2RecruitingTreatmentUlcerative Colitis (UC)1
2TerminatedTreatmentCrohn's Disease (CD)1
2, 3CompletedTreatmentRheumatoid Arthritis1
2, 3RecruitingTreatmentGeneralized Pustular Psoriasis and Erythrodermic Psoriasis / Psoriasis, Moderate to Severe1
3Active Not RecruitingTreatmentAnkylosing Spondylitis (AS) / Axial Spondyloarthrithis1
3Active Not RecruitingTreatmentInterstitial Cystitis1
3Active Not RecruitingTreatmentNonradiographic Axial Spondyloarthritis / Nr-axSpA / Spondyloarthritis, Axial1
3Active Not RecruitingTreatmentPlaque Psoriasis / Psoriasis3
3Active Not RecruitingTreatmentPolyarticular-course Juvenile Idiopathic Arthritis (JIA)1
3Active Not RecruitingTreatmentRheumatoid Arthritis1
3CompletedNot AvailableCrohn's Disease (CD)2
3CompletedBasic ScienceRheumatoid Arthritis1
3CompletedTreatmentActive Rheumatoid Arthritis1
3CompletedTreatmentCrohn's Disease (CD)8
3CompletedTreatmentPsoriatic Arthritis1
3CompletedTreatmentRheumatoid Arthritis21
3CompletedTreatmentSpondyloarthropathies1
3RecruitingTreatmentRheumatoid Arthritis1
3TerminatedTreatmentCrohn's Disease (CD)2
3TerminatedTreatmentRheumatoid Arthritis1
3Unknown StatusTreatmentCrohn's Disease (CD)1
3WithdrawnTreatmentCrohn's Disease (CD)2
4CompletedNot AvailableRheumatoid Arthritis1
4CompletedTreatmentRheumatoid Arthritis7
4Enrolling by InvitationNot AvailableRheumatoid Arthritis1
4Not Yet RecruitingTreatmentCrohn's Disease (CD)1
4Not Yet RecruitingTreatmentRheumatoid Arthritis1
4RecruitingBasic ScienceRheumatoid Arthritis1
4RecruitingTreatmentAnterior Uveitis (AU) / Axial Spondyloarthritis (AxSpA)1
4RecruitingTreatmentRheumatoid Arthritis4
4TerminatedNot AvailableCrohns Disease1
4TerminatedTreatmentCrohn's Disease (CD)1
4Unknown StatusTreatmentAnkylosing Spondylitis (AS) / Hypertensive / Psoriatic Arthritis / Rheumatoid Arthritis1
4Unknown StatusTreatmentCrohn's Disease (CD)1
Not AvailableActive Not RecruitingNot AvailableCrohn's Disease (CD)1
Not AvailableCompletedTreatmentCrohn's Disease (CD)1
Not AvailableRecruitingNot AvailableCrohn's Disease (CD) / Inflammatory Bowel Diseases (IBD)1
Not AvailableRecruitingNot AvailableRheumatoid Arthritis2
Not AvailableRecruitingPreventionCardiovascular Disease (CVD) / Rheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous200 mg
Injection, solutionSubcutaneous200 mg/mL
Kit
SolutionSubcutaneous200 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2380298No2010-09-282021-06-05Canada

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Neutralizer
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
References
  1. Chimenti MS, Saraceno R, Chiricozzi A, Giunta A, Chimenti S, Perricone R: Profile of certolizumab and its potential in the treatment of psoriatic arthritis. Drug Des Devel Ther. 2013 Apr 15;7:339-48. doi: 10.2147/DDDT.S31658. Print 2013. [PubMed:23620660]

Drug created on June 11, 2013 00:11 / Updated on November 19, 2017 20:34