NAV

Abatacept

Identification

Summary

Abatacept is a disease-modifying antirheumatic drug (DMARD) used in the management of rheumatic conditions, such as rheumatoid or psoriatic arthritis, and for the prophylaxis of acute graft-versus-host disease.

Brand Names
Orencia
Generic Name
Abatacept
DrugBank Accession Number
DB01281
Background

Abatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1).11,12 Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077).

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Fusion proteins
Protein Chemical Formula
C3498H5458N922O1090S32
Protein Average Weight
92300.0 Da (with glycosylation)
Sequences
>Abatacept monomer sequence
MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTF
LDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPC
PDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED
PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA
PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
  • Abatacept
  • Abatacept recombinant
External IDs
  • BMS-188667
  • CTLA4-IGG4M
  • RG-1046
  • RG-2077
  • RG1046
  • RG2077

Pharmacology

Indication

Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and in patients ≥2 years of age for the treatment of active psoriatic arthritis.13 In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis.11

Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor.11

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1. The Fc portion of the drug consists of the hinge region, the CH2 domain, and the CH3 domain of IgG1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy.

Mechanism of action

Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis.

TargetActionsOrganism
AT-lymphocyte activation antigen CD80
antagonist
Humans
AT-lymphocyte activation antigen CD86
antagonist
Humans
UCytotoxic T-lymphocyte protein 4
inhibitor
Humans
Absorption

When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%.

Volume of distribution
  • 0.07 L/kg [RA Patients, IV administration]
  • 0.09 L/kg [Healthy Subjects, IV administration]
  • 0.11 L/kg [RA patients, subcutaneous administration]
Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Kidney and liver

Half-life

16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients.

Clearance
  • 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion]
  • 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions]
  • 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight.
Adverse Effects
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Toxicity

Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Abatacept.
AbrocitinibThe metabolism of Abrocitinib can be increased when combined with Abatacept.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Abatacept.
AcebutololThe metabolism of Acebutolol can be increased when combined with Abatacept.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Abatacept.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Abatacept.
AcetohexamideThe metabolism of Acetohexamide can be increased when combined with Abatacept.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be increased when combined with Abatacept.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Abatacept.
AdalimumabThe risk or severity of infection can be increased when Adalimumab is combined with Abatacept.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OrenciaInjection, powder, for solution250 mgIntravenousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag
OrenciaInjection, solution125 mgSubcutaneousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag
OrenciaInjection, solution50 mgSubcutaneousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag
OrenciaInjection, solution125 mgSubcutaneousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag
OrenciaPowder, for solution250 mg / vialIntravenousBristol Myers Squibb2006-08-08Not applicableCanada flag
OrenciaInjection, solution125 mg/1mLSubcutaneousE.R. Squibb & Sons, L.L.C.2011-07-29Not applicableUS flag
OrenciaInjection, solution125 mgSubcutaneousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag
OrenciaInjection, powder, for solution250 mgIntravenousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag
OrenciaInjection, solution125 mgSubcutaneousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag
OrenciaInjection, solution125 mgSubcutaneousBristol Myers Squibb Pharma Eeig2021-02-11Not applicableEU flag

Categories

ATC Codes
L04AA24 — Abatacept
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
7D0YB67S97
CAS number
332348-12-6

References

Synthesis Reference

Sang-Lin Kim, Hyun-Kwang Tan, Sang-Min Lim, Wuk-Sang Ryu, Hahn-Sun Jung, Song-Jae Lee, Cheon-Ik Park, Seung-Hoon Kang, Dong Il Kim, "Plant Recombinant Human CTLA4IG and a Method for Producing the Same." U.S. Patent US20100189717, issued July 29, 2010.

US20100189717
General References
  1. Dall'Era M, Davis J: CTLA4Ig: a novel inhibitor of costimulation. Lupus. 2004;13(5):372-6. [Article]
  2. Moreland L, Bate G, Kirkpatrick P: Abatacept. Nat Rev Drug Discov. 2006 Mar;5(3):185-6. [Article]
  3. Weisman MH, Durez P, Hallegua D, Aranda R, Becker JC, Nuamah I, Vratsanos G, Zhou Y, Moreland LW: Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol. 2006 Nov;33(11):2162-6. Epub 2006 Oct 1. [Article]
  4. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [Article]
  5. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [Article]
  6. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [Article]
  7. Maxwell L, Singh JA: Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007277. doi: 10.1002/14651858.CD007277.pub2. [Article]
  8. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [Article]
  9. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [Article]
  10. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [Article]
  11. FDA Approved Drug Products: Orencia (abatacept) for injection [Link]
  12. Health Canada Approved Drug Products: Orencia (abatacept) for injection [Link]
  13. FDA Approved Drug Products: Orencia (abatacept) for intravenous or subcutaneous injection (October 2023) [Link]
KEGG Drug
D03203
PubChem Substance
46509198
RxNav
614391
ChEMBL
CHEMBL1201823
Therapeutic Targets Database
DAP000867
PharmGKB
PA164747080
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Abatacept

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentPalindromic Rheumatism, Wrist1
4Active Not RecruitingTreatmentRheumatoid Arthritis3
4CompletedBasic ScienceRheumatoid Arthritis1
4CompletedTreatmentDermatomyositis (DM)1
4CompletedTreatmentPrimary Biliary Cholangitis1
4CompletedTreatmentRheumatic Diseases / Rheumatoid Arthritis1
4CompletedTreatmentRheumatoid Arthritis8
4Not Yet RecruitingTreatmentRheumatoid Arthritis1
4RecruitingPreventionCoronavirus Disease 2019 (COVID‑19) / Psoriatic Arthritis / Rheumatoid Arthritis / Spondylarthritis1
4RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
  • Celltrion Inc.
  • E.R. Squibb and Sons LLC
Dosage Forms
FormRouteStrength
SolutionOther262.500 mg
Injection, powder, for solutionIntravenous250 MG
Injection, powder, lyophilized, for solutionIntravenous250 mg/15mL
Injection, solutionParenteral; Subcutaneous125 MG
Injection, solutionParenteral; Subcutaneous50 MG
Injection, solutionParenteral; Subcutaneous87.5 MG
Injection, solutionSubcutaneous125 mg
Injection, solutionSubcutaneous125 mg/1mL
Injection, solutionSubcutaneous50 mg
Injection, solutionSubcutaneous50 mg/0.4mL
Injection, solutionSubcutaneous87.5 mg/0.7mL
Injection, solutionSubcutaneous87.5 mg
Powder250 mg/1vial
Powder, for solutionIntravenous250 mg / vial
SolutionSubcutaneous125 mg / mL
Powder, for solutionIntravenous250 mg
Injection, powder, lyophilized, for solutionIntravenous262.5 MG
InjectionSubcutaneous125 mg
Injection, solution125 mg
SolutionSubcutaneous125 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2110518No2007-05-222012-06-16Canada flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Details1. T-lymphocyte activation antigen CD80
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Involved in the costimulatory signal essential for T-lymphocyte activation. T-cell proliferation and cytokine production is induced by the binding of CD28, binding to CTLA-4 has opposite effects an...
Gene Name
CD80
Uniprot ID
P33681
Uniprot Name
T-lymphocyte activation antigen CD80
Molecular Weight
33047.625 Da
References
  1. Kremer JM: Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis. J Clin Rheumatol. 2005 Jun;11(3 Suppl):S55-62. [Article]
  2. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [Article]
  3. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [Article]
  4. Vincenti F, Luggen M: T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med. 2007;58:347-58. [Article]
  5. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [Article]
  6. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [Article]
  7. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [Article]
  8. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [Article]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Details2. T-lymphocyte activation antigen CD86
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cel...
Gene Name
CD86
Uniprot ID
P42081
Uniprot Name
T-lymphocyte activation antigen CD86
Molecular Weight
37681.97 Da
References
  1. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [Article]
  2. Vincenti F, Luggen M: T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med. 2007;58:347-58. [Article]
  3. Kremer JM: Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis. J Clin Rheumatol. 2005 Jun;11(3 Suppl):S55-62. [Article]
  4. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [Article]
  5. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [Article]
  6. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [Article]
  7. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [Article]
  8. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [Article]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Details3. Cytotoxic T-lymphocyte protein 4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of t...
Gene Name
CTLA4
Uniprot ID
P16410
Uniprot Name
Cytotoxic T-lymphocyte protein 4
Molecular Weight
24655.63 Da
References
  1. Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]

Drug created at May 16, 2007 22:55 / Updated at November 25, 2023 12:39