Abatacept
Identification
- Summary
Abatacept is a disease-modifying antirheumatic drug (DMARD) used for the management of moderate-to-severe active rheumatoid arthritis and active polyarticular juvenile idiopathic arthritis as monotherapy or in combination with other DMARDs.
- 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). 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
For the management of the signs and symptoms of moderate-to-severe active rheumatoid arthritis, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients. It is indicated both as a monotherapy and for use in combination with a continued regimen of DMARDs (not including TNF antagonists). Also used for the management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.
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- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- 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.
Target Actions Organism AT-lymphocyte activation antigen CD80 antagonistHumans AT-lymphocyte activation antigen CD86 antagonistHumans - 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The metabolism of Abemaciclib can be increased when combined with Abatacept. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Abatacept. Acebutolol The metabolism of Acebutolol can be increased when combined with Abatacept. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Abatacept. Acetaminophen The metabolism of Acetaminophen can be increased when combined with Abatacept. Acetohexamide The metabolism of Acetohexamide can be increased when combined with Abatacept. Acetylsalicylic acid The metabolism of Acetylsalicylic acid can be increased when combined with Abatacept. Acyclovir The metabolism of Acyclovir can be increased when combined with Abatacept. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Abatacept. Agomelatine The metabolism of Agomelatine can be increased when combined with Abatacept. 
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- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Orencia Injection, solution 125 mg/1mL Subcutaneous E.R. Squibb & Sons, L.L.C. 2011-07-29 Not applicable US 
Orencia Injection, solution 87.5 mg Subcutaneous Bristol Myers Squibb Pharma Eeig 2021-02-11 Not applicable EU 
Orencia Injection, solution 125 mg Subcutaneous Bristol Myers Squibb Pharma Eeig 2021-02-11 Not applicable EU Orencia Solution 125 mg / mL Subcutaneous Bristol Myers Squibb 2013-05-09 Not applicable Canada 
Orencia Injection, solution 125 mg Subcutaneous Bristol Myers Squibb Pharma Eeig 2021-02-11 Not applicable EU Orencia Injection, solution 87.5 mg/0.7mL Subcutaneous E.R. Squibb & Sons, L.L.C. 2011-07-29 Not applicable US Orencia Injection, solution 125 mg Subcutaneous Bristol Myers Squibb Pharma Eeig 2021-02-11 Not applicable EU Orencia Injection, powder, for solution 250 mg Intravenous Bristol Myers Squibb Pharma Eeig 2021-02-11 Not applicable EU Orencia Injection, powder, lyophilized, for solution 250 mg/15mL Intravenous E.R. Squibb & Sons, L.L.C. 2009-01-01 Not applicable US Orencia Injection, solution 50 mg Subcutaneous Bristol Myers Squibb Pharma Eeig 2021-02-11 Not applicable EU
Categories
- ATC Codes
- L04AA24 — Abatacept
- Drug Categories
- Agents reducing cytokine levels
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- Biologics for Rheumatoid Arthritis Treatment
- Blood Proteins
- CD80-directed Antibody Interactions
- CD86-directed Antibody Interactions
- Decreased Cytokine Activity
- Disease-modifying Antirheumatic Agents
- Globulins
- Immunoconjugates
- Immunologic Factors
- Immunoproteins
- Immunosuppressive Agents
- Noxae
- Proteins
- Selective Immunosuppressants
- Selective T Cell Costimulation Modulator
- Serum Globulins
- Toxic Actions
- 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
- Dall'Era M, Davis J: CTLA4Ig: a novel inhibitor of costimulation. Lupus. 2004;13(5):372-6. [Article]
- Moreland L, Bate G, Kirkpatrick P: Abatacept. Nat Rev Drug Discov. 2006 Mar;5(3):185-6. [Article]
- 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]
- Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [Article]
- 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]
- 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]
- Maxwell L, Singh JA: Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007277. doi: 10.1002/14651858.CD007277.pub2. [Article]
- Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [Article]
- Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [Article]
- Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [Article]
- External Links
- KEGG Drug
- D03203
- PubChem Substance
- 46509198
- 614391
- ChEMBL
- CHEMBL1201823
- Therapeutic Targets Database
- DAP000867
- PharmGKB
- PA164747080
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Abatacept
- FDA label
- Download (108 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Rheumatoid Arthritis 2 4 Completed Basic Science Rheumatoid Arthritis 1 4 Completed Treatment Dermatomyositis 1 4 Completed Treatment Primary Biliary Cholangitis 1 4 Completed Treatment Rheumatoid Arthritis 6 4 Enrolling by Invitation Other Rheumatoid Arthritis 1 4 Not Yet Recruiting Treatment Palindromic Rheumatism, Wrist 1 4 Not Yet Recruiting Treatment Rheumatoid Arthritis 1 4 Recruiting Diagnostic Evaluate Bone Changes in Patients With PsA 1 4 Recruiting Treatment Myocardial Inflammation / Rheumatoid Arthritis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Bristol-Myers Squibb Co.
- Celltrion Inc.
- E.R. Squibb and Sons LLC
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous Injection, powder, for solution Intravenous 250 mg Injection, powder, lyophilized, for solution Intravenous 250 mg/15mL Injection, solution Parenteral; Subcutaneous Injection, solution Subcutaneous 125 mg/1mL Injection, solution Subcutaneous 125 mg Injection, solution Subcutaneous 50 mg Injection, solution Subcutaneous 50 mg/0.4mL Injection, solution Subcutaneous 87.5 mg Injection, solution Subcutaneous 87.5 mg/0.7mL Powder 250 mg/1vial Powder, for solution Intravenous 250 mg / vial Solution Subcutaneous 125 mg / mL Injection, powder, lyophilized, for solution Intravenous 262.5 mg Powder, for solution Intravenous Injection, solution Solution Subcutaneous 125 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2110518 No 2007-05-22 2012-06-16 Canada
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- 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
- 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]
- Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [Article]
- 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]
- 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]
- 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]
- Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [Article]
- Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [Article]
- Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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
- 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]
- 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]
- 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]
- Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [Article]
- 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]
- Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [Article]
- Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [Article]
- Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Drug created on May 16, 2007 22:55 / Updated on July 24, 2021 14:58