Ustekinumab

Identification

Name
Ustekinumab
Accession Number
DB05679
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Ustekinumab, is a human immunosuppressive drug developed by the biotechnology company Centocor. It is a laboratory-manufactured, monoclonal antibody directed against interleukins IL-12 and IL-23. Since 2009, ustekinumab has been approved in US, Canada, and Europe for the treatment of plaque psoriasis and psoriatic arthritis. In September 2016, Janssen announced that the FDA approved the medication for the treatment of moderate-severe Crohn's disease.

Protein structure
Db05679
Protein chemical formula
Anti-(human interleukin 12 p40 subunit) (human monoclonal CNTO 1275 γ1-chain)-immunoglobulin G1 disulfide with human monoclonal CNTO 1275 κ-chain dimer
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • Stelera
External IDs
CNTO 1275 / CNTO-1275 / CNTO1275 / L04AC05 / TT 20 / TT-20 / TT20
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
StelaraInjection, solution45 mgSubcutaneousJanssen Cilag International Nv2009-01-16Not applicableEu
StelaraInjection, solution90 mg/mLSubcutaneousJanssen Biotech, Inc.2009-09-25Not applicableUs
StelaraInjection, solution90 mgSubcutaneousJanssen Cilag International Nv2009-01-16Not applicableEu
StelaraSolution5 mgIntravenousJanssen Pharmaceuticals2016-12-21Not applicableCanada
StelaraInjection, solution90 mgSubcutaneousJanssen Cilag International Nv2009-01-16Not applicableEu
StelaraSolution130 mg/26mLIntravenousJanssen Biotech, Inc.2016-09-23Not applicableUs
StelaraSolution45 mgSubcutaneousJanssen Pharmaceuticals2009-01-05Not applicableCanada
StelaraInjection, solution45 mg/.5mLSubcutaneousJanssen Biotech, Inc.2009-09-25Not applicableUs
StelaraInjection, solution45 mgSubcutaneousJanssen Cilag International Nv2009-01-16Not applicableEu
StelaraSolution90 mgSubcutaneousJanssen Pharmaceuticals2013-01-07Not applicableCanada
Categories
UNII
FU77B4U5Z0
CAS number
815610-63-0

Pharmacology

Indication

Ustekinumab is indicated for management of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy; or is used alone or in conjunction with methotrexate for the management of active psoriatic arthritis in adults. The FDA approved the use of ustekinumab in September 2016 for the treatment of moderate to severe Crohn's disease. The use of ustekinumab may improve short term clinical response but not clinical remission in moderate to severe Crohn's disease.

Structured Indications
Pharmacodynamics
Not Available
Mechanism of action

Ustekinumab is a human IgG1-kappa monoclonal antibody designed to interfere with the triggering of the body's inflammatory response through the suppression of certain cytokines. Specifically, ustekinumab blocks interleukin IL-12 and IL-23 by binding with high affinity and specificity to the p40 subunit of IL-12 and IL-23, therefore disrupting the proinflammatory pathway that contributes to several chronic diseases. In a more minor role, ustekinumab also interferes with the expression of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-inducible protein-10 (IP-10), and interleukin IL-8.

TargetActionsOrganism
AInterleukin-12 subunit beta
antibody
Human
AInterleukin-23Not AvailableHuman
Absorption

Following a subcutaneous administration of a single 45 or 90mg dose (in patients with psoriasis), peak serum concentrations are achieved in a median of 13.5 or 7 days, respectively.

Volume of distribution

Plaque psoriasis and psoriatic arthritis dosing: 45mg: ~0.161L/kg 90mg: ~0.179L/kg

Protein binding
Not Available
Metabolism

Expected to be degraded into small peptides and amino acids.

Route of elimination
Not Available
Half life

Mean half-life: 14.9–45.6 days following IV and sub-Q administration in patients with psoriasis.

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

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Ustekinumab.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Ustekinumab is combined with Belimumab.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 Ustekinumab.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 Ustekinumab.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Ustekinumab.Approved
FingolimodUstekinumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Ustekinumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Ustekinumab.Investigational
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Ustekinumab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Ustekinumab.Approved, Withdrawn
InfliximabUstekinumab may increase the immunosuppressive activities of Infliximab.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Ustekinumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Ustekinumab.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Ustekinumab is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Ustekinumab is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Ustekinumab.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Ustekinumab.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Ustekinumab.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Ustekinumab.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Ustekinumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Ustekinumab.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Ustekinumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Ustekinumab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Ustekinumab.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Ustekinumab.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Ustekinumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Ustekinumab.Investigational
TofacitinibUstekinumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Ustekinumab.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Ustekinumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Ustekinumab.Approved
Food Interactions
No interactions found.

References

General References
  1. Wittig BM: Drug evaluation: CNTO-1275, a mAb against IL-12/IL-23p40 for the potential treatment of inflammatory diseases. Curr Opin Investig Drugs. 2007 Nov;8(11):947-54. [PubMed:17979029]
  2. Boker A, Kimball AB, Rolz-Cruz G: Biologicals in the treatment of psoriasis. Curr Opin Investig Drugs. 2007 Nov;8(11):939-46. [PubMed:17979028]
  3. Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U: Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275. Cell Immunol. 2007 May;247(1):1-11. Epub 2007 Aug 29. [PubMed:17761156]
  4. Khanna R, Chande N, Vermeire S, Sandborn WJ, Parker CE, Feagan BG: The Next Wave of Biological Agents for the Treatment of IBD: Evidence from Cochrane Reviews. Inflamm Bowel Dis. 2016 Jul;22(7):1737-43. doi: 10.1097/MIB.0000000000000808. [PubMed:27306074]
  5. Engel T, Kopylov U: Ustekinumab in Crohn's disease: evidence to date and place in therapy. Ther Adv Chronic Dis. 2016 Jul;7(4):208-14. doi: 10.1177/2040622316653306. Epub 2016 Jul 6. [PubMed:27433311]
External Links
KEGG Drug
D09214
PubChem Substance
347910190
ChEMBL
CHEMBL1201835
Drugs.com
Drugs.com Drug Page
Wikipedia
Ustekinumab
ATC Codes
L04AC05 — Ustekinumab
AHFS Codes
  • 92:00.00 — Miscellaneous Therapeutic Agents
FDA label
Download (7.26 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentPsoriasis2
1RecruitingTreatmentCrohn's Disease (CD)1
1, 2Active Not RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
1, 2RecruitingTreatmentChronic Functional Diarrhea / CVID / Enteropathy / Malabsorption / Maldigestion1
1, 2RecruitingTreatmentGiant Cells Arteritis / Temporal Arteritis1
1, 2WithdrawnTreatmentUveitis1
2Active Not RecruitingTreatmentAtopic Dermatitis (AD)1
2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD)1
2Active Not RecruitingTreatmentLupus Erythematosus, Systemic / Systemic Lupus Erythematosus (SLE)1
2Active Not RecruitingTreatmentPsoriasis1
2Active Not RecruitingTreatmentPsoriatic Arthritis1
2CompletedTreatmentAnkylosing Spondylitis (AS)1
2CompletedTreatmentAtopic Dermatitis (AD)1
2CompletedTreatmentCrohn's Disease (CD)2
2CompletedTreatmentDisseminated Sclerosis1
2CompletedTreatmentHidradenitis Suppurativa (HS)1
2CompletedTreatmentPrimary Biliary Cirrhosis (PBC)1
2CompletedTreatmentPsoriasis2
2CompletedTreatmentPsoriatic Arthritis1
2CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentSarcoidosis1
2RecruitingTreatmentBehçet's Disease1
2RecruitingTreatmentCrohn's Disease (CD)1
2RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
2RecruitingTreatmentUveitis1
3Active Not RecruitingNot AvailableInflammatory Bowel Diseases (IBD) / Ulcerative Colitis (UC)1
3Active Not RecruitingTreatmentColitis / Crohn's Disease (CD) / Inflammatory Bowel Diseases (IBD)1
3Active Not RecruitingTreatmentPlaque Psoriasis2
3CompletedTreatmentChronic Plaque Type Psoriasis1
3CompletedTreatmentPsoriasis9
3CompletedTreatmentPsoriatic Arthritis2
3RecruitingTreatmentCrohn's Disease (CD)1
3RecruitingTreatmentPsoriasis1
3RecruitingTreatmentPsoriatic Arthritis1
3TerminatedTreatmentModerate to Severe Plaque Psoriasis2
3TerminatedTreatmentPalmo-Plantar Pustular Psoriasis / Palmo-Plantar Pustulosis1
3TerminatedTreatmentPsoriasis1
3TerminatedTreatmentSpondyloarthritis, Axial2
4Active Not RecruitingTreatmentCardiovascular Disease (CVD) / Psoriasis1
4CompletedNot AvailablePlaque Psoriasis1
4CompletedTreatmentPsoriasis2
4RecruitingTreatmentPsoriasis With Cell-derived Microparticles1
4Unknown StatusTreatmentPlaque Psoriasis / Scalp Psoriasis1
4Unknown StatusTreatmentPsoriasis1
Not AvailableActive Not RecruitingNot AvailablePsoriasis1
Not AvailableActive Not RecruitingNot AvailablePsoriasis / Psoriatic Arthritis1
Not AvailableCompletedNot AvailableAtherosclerosis / Atopic Dermatitis (AD) / Psoriasis1
Not AvailableCompletedNot AvailableInflammatory Reaction / Psoriasis1
Not AvailableCompletedNot AvailablePsoriasis1
Not AvailableCompletedTreatmentModerate to Severe Palmar Plantar Psoriasis1
Not AvailableNot Yet RecruitingNot AvailableInflammatory Bowel Diseases (IBD)1
Not AvailableRecruitingNot AvailableAlzheimer's Disease (AD)1
Not AvailableRecruitingNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableRecruitingNot AvailablePsoriasis2
Not AvailableRecruitingNot AvailablePsoriatic Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous45 mg
Injection, solutionSubcutaneous45 mg/.5mL
Injection, solutionSubcutaneous90 mg
Injection, solutionSubcutaneous90 mg/mL
SolutionIntravenous130 mg/26mL
SolutionIntravenous5 mg
SolutionSubcutaneous45 mg
SolutionSubcutaneous90 mg
Prices
Not Available
Patents
Not Available

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
Antibody
General Function
Protein heterodimerization activity
Specific Function
Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC....
Gene Name
IL12B
Uniprot ID
P29460
Uniprot Name
Interleukin-12 subunit beta
Molecular Weight
37168.645 Da
References
  1. Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U: Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275. Cell Immunol. 2007 May;247(1):1-11. Epub 2007 Aug 29. [PubMed:17761156]
  2. Wittig BM: Drug evaluation: CNTO-1275, a mAb against IL-12/IL-23p40 for the potential treatment of inflammatory diseases. Curr Opin Investig Drugs. 2007 Nov;8(11):947-54. [PubMed:17979029]
Kind
Protein group
Organism
Human
Pharmacological action
Yes
General Function
Protein heterodimerization activity
Specific Function
Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC....

Components:
References
  1. Engel T, Kopylov U: Ustekinumab in Crohn's disease: evidence to date and place in therapy. Ther Adv Chronic Dis. 2016 Jul;7(4):208-14. doi: 10.1177/2040622316653306. Epub 2016 Jul 6. [PubMed:27433311]
  2. Khanna R, Chande N, Vermeire S, Sandborn WJ, Parker CE, Feagan BG: The Next Wave of Biological Agents for the Treatment of IBD: Evidence from Cochrane Reviews. Inflamm Bowel Dis. 2016 Jul;22(7):1737-43. doi: 10.1097/MIB.0000000000000808. [PubMed:27306074]

Drug created on November 18, 2007 11:26 / Updated on November 19, 2017 20:34