Golimumab

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
SimponiSolution50 mgSubcutaneousJanssen Pharmaceuticals2009-06-22Not applicableCanada
SimponiSolution100 mgSubcutaneousJanssen Pharmaceuticals2013-10-03Not applicableCanada
SimponiInjection, solution50 mg/0.5mLSubcutaneousJanssen Biotech, Inc.2009-04-25Not applicableUs
SimponiInjection, solution100 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
SimponiInjection, solution50 mgSubcutaneousJanssen Biologics B.V.2009-10-01Not applicableEu
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, solution50 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.

Associated Conditions
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
DrugInteraction
AbataceptThe risk or severity of infection can be increased when Golimumab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Golimumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Golimumab.
AlclometasoneThe risk or severity of adverse effects can be increased when Golimumab is combined with Alclometasone.
AldesleukinThe risk or severity of adverse effects can be increased when Golimumab is combined with Aldesleukin.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Golimumab.
AmcinonideThe risk or severity of adverse effects can be increased when Golimumab is combined with Amcinonide.
AmsacrineThe risk or severity of adverse effects can be increased when Golimumab is combined with Amsacrine.
AnakinraThe risk or severity of adverse effects can be increased when Golimumab is combined with Anakinra.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Golimumab is combined with Anthrax immune globulin human.
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
0RecruitingBasic ScienceDiabetes, Diabetes Mellitus Type 11
1Active Not RecruitingTreatmentUlcerative Colitis (UC)1
1CompletedTreatmentHealthy Adult Chinese Males1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentRheumatoid Arthritis1
1RecruitingTreatmentPre-Symptomatic Type 1 Diabetes1
1, 2TerminatedTreatmentAutoimmune Inner Ear Disease1
2Active Not RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
2CompletedTreatmentAsthma Bronchial1
2CompletedTreatmentRheumatoid Arthritis2
2CompletedTreatmentSarcoidosis1
2CompletedTreatmentUlcerative Colitis (UC)1
2RecruitingTreatmentAnkylosing Spondylitis (AS)1
2RecruitingTreatmentUlcerative Colitis (UC)1
2TerminatedTreatmentRheumatoid Arthritis1
2, 3CompletedTreatmentUlcerative Colitis (UC)1
2, 3TerminatedTreatmentUlcerative Colitis (UC)1
3Active Not RecruitingTreatmentJuvenile Idiopathic Arthritis (JIA)1
3CompletedTreatmentAnkylosing Spondylitis (AS)4
3CompletedTreatmentArthritis / Autoimmune Diseases / Rheumatoid Arthritis1
3CompletedTreatmentPsoriatic Arthritis3
3CompletedTreatmentRheumatoid Arthritis8
3CompletedTreatmentUlcerative Colitis (UC)2
3Not Yet RecruitingTreatmentSpondyloarthritis, Axial1
3Not Yet RecruitingTreatmentUlcerative Colitis (UC)1
3RecruitingTreatmentPsoriatic Arthritis1
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 RecruitingTreatmentUlcerative Colitis (UC)1
4RecruitingOtherHepatosplenic T-Cell Lymphoma1
4RecruitingTreatmentAnkylosing Spondylitis (AS)1
4RecruitingTreatmentColitis1
4RecruitingTreatmentRheumatoid Arthritis3
4RecruitingTreatmentUlcerative Colitis (UC)2
4TerminatedNot AvailableRheumatoid Arthritis1
4Unknown StatusDiagnosticUlcerative Colitis (UC)1
4WithdrawnNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableActive Not RecruitingNot AvailableAnkylosing Spondylitis (AS) / Coxitis1
Not AvailableActive Not RecruitingNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableActive Not RecruitingNot AvailableRheumatoid Arthritis1
Not AvailableCompletedNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableCompletedNot AvailablePsoriatic Arthritis / Rheumatoid Arthritis / Spondyloarthritis1
Not AvailableCompletedNot AvailableSpondyloarthritis / Ultrasonography1
Not AvailableRecruitingNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableRecruitingNot AvailablePsoriatic Arthritis1
Not AvailableRecruitingNot AvailableRheumatoid Arthritis2
Not AvailableRecruitingNot AvailableUlcerative Colitis (UC)1
Not AvailableTerminatedNot AvailableRheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous100 mg/1mL
Injection, solutionSubcutaneous100 mg
Injection, solutionSubcutaneous50 mg/0.5mL
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 September 21, 2018 20:42