Identification

Name
Golimumab
Accession Number
DB06674
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Golimumab is a human IgG1қ monoclonal antibody derived from immunizing genetically engineered mice with human TNFα. Golimumab binds and inhibits soluble and transmembrane human TNFα. Increased TNFα is associated with chronic inflammation. Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications. In the U.S. and Canada, golimumab is marketed under the brand name Simponi®. The FDA label includes a black box warning of serious infections and malignancy. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed.

Protein structure
Db06674
Protein chemical formula
C6530H10068N1752O2026S44
Protein average weight
146943.1937 Da
Sequences
Not Available
Synonyms
Not Available
External IDs
CNTO 148 / CNTO-148
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SimponiInjection, solution100 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
SimponiSolution100 mgSubcutaneousJanssen Pharmaceuticals2013-10-03Not applicableCanada
SimponiInjection, solution50 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
SimponiSolution50 mgSubcutaneousJanssen Pharmaceuticals2009-06-22Not applicableCanada
SimponiInjection, solution100 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
SimponiInjection, solution100 mg/mLSubcutaneousJanssen Biotech, Inc.2013-05-15Not applicableUs
SimponiInjection, solution50 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
SimponiInjection, solution50 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
SimponiInjection, solution100 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
SimponiSolution100 mgSubcutaneousJanssen Pharmaceuticals2013-10-03Not applicableCanada
Categories
UNII
91X1KLU43E
CAS number
476181-74-5

Pharmacology

Indication

Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (iv) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications.

Structured Indications
Pharmacodynamics

Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα). In areas such as the joints and blood, increased TNFα is associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Thus golimumab decreases the inflammation in these conditions. Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined.

Mechanism of action

As a human monoclonal antibody, golimumab binds and inhibits soluble and transmembrane human TNFα. Inhibition of TNFα prevents it binding to its receptors, which prevents both leukocyte infiltration through prevention of cell adhesion proteins such as E-selectin, ICAM-1 and VCAM-1, and pro-inflammatory cytokine secretion such as IL-6, IL-8, G-CSF and GM-CSF in vitro. Consequently, in patients with chronic inflammatory conditions, decreases in ICAM-1 and IL-6 as well as C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) were observed.

TargetActionsOrganism
ATumor necrosis factor
antibody
Human
Absorption

After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2 to 6 days and has an approximate bioavailability of 53%. In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 μg/mL.

Volume of distribution

After IV administration, golimumab has a volume of distribution of about 58 to 126 mL/kg. This means that golimumab stays mostly in the circulatory system.

Protein binding

Plasma protein binding was not quantified.

Metabolism

The metabolism of golimumab has yet to be determined.

Route of elimination

The route of elimination for golimumab has yet to be determined.

Half life

Golimumab has a long half-life of about 2 weeks.

Clearance

After one IV dose of golimumab, the systemic clearance was about 4.9 to 6.7 mL/day/kg.

Toxicity

The FDA label includes a black box warning of serious infections and malignancy. Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections. Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed.

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 Golimumab is combined with Abatacept.Approved
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Golimumab.Approved
AnakinraThe risk or severity of adverse effects can be increased when Golimumab is combined with Anakinra.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Golimumab.Investigational
CanakinumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Canakinumab.Approved, Investigational
Certolizumab pegolGolimumab may increase the immunosuppressive activities of Certolizumab pegol.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Golimumab.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 Golimumab.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Golimumab.Approved
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Golimumab.Approved, Investigational
FingolimodGolimumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Golimumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Golimumab.Investigational
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Golimumab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Golimumab.Approved, Withdrawn
InfliximabGolimumab may increase the immunosuppressive activities of Infliximab.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Golimumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Golimumab.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Golimumab is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Golimumab.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Golimumab.Approved
RilonaceptThe risk or severity of adverse effects can be increased when Golimumab is combined with Rilonacept.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Golimumab.Investigational
RituximabThe risk or severity of adverse effects can be increased when Golimumab is combined with Rituximab.Approved
RoflumilastRoflumilast may increase the immunosuppressive activities of Golimumab.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Golimumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Golimumab.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Golimumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Golimumab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Golimumab.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Golimumab.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Golimumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Golimumab.Investigational
TocilizumabTocilizumab may increase the immunosuppressive activities of Golimumab.Approved
TofacitinibThe risk or severity of adverse effects can be increased when Golimumab is combined with Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Golimumab.Approved, Investigational
VedolizumabThe risk or severity of infection can be increased when Golimumab is combined with Vedolizumab.Approved
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Golimumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Golimumab.Approved
Food Interactions
  • Since golimumab is administered by subcutaneous injection, there are no food effects.

References

Synthesis Reference

Zhou H, Jang H, Fleischmann RM, Bouman-Thio E, Xu Z, Marini JC, Pendley C, Jiao Q, Shankar G, Marciniak SJ, Cohen SB, Rahman MU, Baker D, Mascelli MA, Davis HM, Everitt DE: Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol. 2007 Mar;47(3):383-96.

General References
  1. Oldfield V, Plosker GL: Golimumab: in the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. BioDrugs. 2009;23(2):125-35. doi: 10.2165/00063030-200923020-00005. [PubMed:19489653]
  2. Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Jarnerot G, Rutgeerts P: Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):96-109.e1. doi: 10.1053/j.gastro.2013.06.010. Epub 2013 Jun 14. [PubMed:23770005]
External Links
KEGG Drug
D04358
PubChem Substance
347910358
ChEMBL
CHEMBL1201833
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Golimumab
ATC Codes
L04AB06 — Golimumab
AHFS Codes
  • 92:36.00 — Disease-modifying Antirheumatic Agents
FDA label
Download (1.9 MB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentUlcerative Colitis (UC)1
1CompletedTreatmentHealthy Adult Chinese Males1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentRheumatoid Arthritis1
1RecruitingTreatmentPre-Symptomatic Type 1 Diabetes1
1, 2TerminatedTreatmentAutoimmune Inner Ear Disease1
2CompletedTreatmentAsthma Bronchial1
2CompletedTreatmentRheumatoid Arthritis2
2CompletedTreatmentSarcoidosis1
2CompletedTreatmentUlcerative Colitis (UC)1
2Not Yet RecruitingTreatmentUlcerative Colitis (UC)1
2RecruitingTreatmentAnkylosing Spondylitis (AS)1
2RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
2TerminatedTreatmentRheumatoid Arthritis1
2, 3CompletedTreatmentUlcerative Colitis (UC)1
2, 3TerminatedTreatmentUlcerative Colitis (UC)1
3CompletedTreatmentAnkylosing Spondylitis (AS)4
3CompletedTreatmentArthritis / Autoimmune Diseases / Rheumatoid Arthritis1
3CompletedTreatmentPsoriatic Arthritis2
3CompletedTreatmentRheumatoid Arthritis8
3CompletedTreatmentUlcerative Colitis (UC)2
3Not Yet RecruitingTreatmentSpondyloarthritis, Axial1
3RecruitingTreatmentJuvenile Idiopathic Arthritis (JIA)1
3RecruitingTreatmentPsoriatic Arthritis2
3TerminatedTreatmentJuvenile Idiopathic Arthritis (JIA)1
3TerminatedTreatmentRheumatoid Arthritis1
3TerminatedTreatmentSpondyloarthritis, Axial2
3Unknown StatusTreatmentPeripheral Spondylarthritis1
4CompletedDiagnosticUlcerative Colitis (UC)1
4CompletedTreatmentAnkylosing Spondylitis (AS)2
4CompletedTreatmentRheumatoid Arthritis1
4CompletedTreatmentSpondyloarthropathies1
4CompletedTreatmentUlcerative Colitis (UC)1
4Not Yet RecruitingTreatmentRheumatoid Arthritis1
4Not Yet RecruitingTreatmentUlcerative Colitis (UC)2
4RecruitingOtherHepatosplenic T-Cell Lymphoma1
4RecruitingTreatmentAnkylosing Spondylitis (AS)1
4RecruitingTreatmentColitis1
4RecruitingTreatmentRheumatoid Arthritis2
4RecruitingTreatmentUlcerative Colitis (UC)1
4TerminatedNot AvailableRheumatoid Arthritis1
4Unknown StatusDiagnosticUlcerative Colitis (UC)1
4WithdrawnNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableActive Not RecruitingNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableCompletedNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableCompletedNot AvailableSpondyloarthritis / Ultrasonography1
Not AvailableRecruitingNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableRecruitingNot AvailablePsoriatic Arthritis1
Not AvailableRecruitingNot AvailableRheumatoid Arthritis3
Not AvailableRecruitingNot AvailableUlcerative Colitis (UC)1
Not AvailableTerminatedNot AvailableRheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous100 mg/mL
Injection, solutionSubcutaneous100 mg
Injection, solutionSubcutaneous50 mg/.5mL
Injection, solutionSubcutaneous50 mg
SolutionSubcutaneous100 mg
SolutionSubcutaneous50 mg
SolutionIntravenous50 mg/4mL
SolutionIntravenous50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
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
Antibody
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. Mittal M, Raychaudhuri SP: Golimumab and certolizumab: the two new anti-tumor necrosis factor kids on the block. Indian J Dermatol Venereol Leprol. 2010 Nov-Dec;76(6):602-8; quiz 609. doi: 10.4103/0378-6323.72445. [PubMed:21079302]

Drug created on March 19, 2008 10:47 / Updated on November 19, 2017 20:34