Identification
NameCertolizumab pegol
Accession NumberDB08904
TypeBiotech
GroupsApproved
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 structureNo structure small
Related Articles
Protein chemical formulaC2115H3252N556O673S16
Protein average weight91000.0 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
External IDs Not Available
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaSolution200 mgSubcutaneousUcb Inc2009-08-31Not applicableCanada
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaKitUcb Inc2008-04-20Not applicableUs
CimziaInjection, solution200 mgSubcutaneousUcb Pharma Sa2009-10-01Not applicableEu
CimziaInjection, solution200 mg/mLSubcutaneousUcb Inc2009-05-14Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIUMD07X179E
CAS number428863-50-7
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Tumor necrosis factorProteinyes
neutralizer
HumanP01375 details
Related Articles
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 bindingNot 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
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbataceptThe risk or severity of adverse effects 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 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
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 risk or severity of adverse effects can be increased when Certolizumab pegol is combined with G17DT.Investigational
GolimumabGolimumab may increase the immunosuppressive activities of Certolizumab pegol.Approved
InfliximabInfliximab may increase the immunosuppressive activities of Certolizumab pegol.Approved
INGN 201The risk or severity of adverse effects can be increased when Certolizumab pegol is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Certolizumab pegol is combined with INGN 225.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.Investigational
RilonaceptThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Rilonacept.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with CDX-110.Investigational
RituximabRituximab may increase the immunosuppressive activities of Certolizumab pegol.Approved
RoflumilastRoflumilast may increase the immunosuppressive activities of Certolizumab pegol.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Certolizumab pegol.Approved
SRP 299The risk or severity of adverse effects can be increased when Certolizumab pegol is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Certolizumab pegol.Approved, 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 adverse effects can be increased when Certolizumab pegol is combined with Vedolizumab.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesL04AB05 — Certolizumab pegol
AHFS Codes
  • 56:92
PDB EntriesNot Available
FDA labelDownload (595 KB)
MSDSDownload (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
2Not Yet RecruitingTreatmentAnkylosing Spondylitis (AS)1
2RecruitingPreventionAntiphospholipid Syndrome in Pregnancy / Complications, Pregnancy / High Risk Pregnancies / Lupus Anticoagulant Disorder1
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 AvailableCompletedTreatmentCrohn's Disease (CD)1
Not AvailableEnrolling by InvitationNot AvailableCrohn'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
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous200 mg
Injection, solutionSubcutaneous200 mg/mL
Kit
SolutionSubcutaneous200 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2380298 No2010-09-282021-06-05Canada
Properties
StateSolid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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 action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs ...
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 August 17, 2016 12:24