Abatacept
| Clinical data | |
|---|---|
| Trade names | Orencia |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a606016 |
| License data | |
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| Routes of administration | Intravenous,subcutaneous |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokineticdata | |
| Eliminationhalf-life | 13.1 days |
| Identifiers | |
| CAS Number | |
| DrugBank | |
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| UNII | |
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| Chemical and physical data | |
| Formula | C3498H5458N922O1090S32 |
| Molar mass | 78895.43g·mol−1 |
  (what is this?)(verify) | |
Abatacept,sold under the brand nameOrencia,is a medication used to treat autoimmune diseases likerheumatoid arthritis,by interfering with the immune activity ofT cells.[1][3]It is a modified antibody.[1][3]
Abatacept is afusion proteincomposed of the Fc region of theimmunoglobulinIgG1 fused to the extracellular domain ofCTLA-4.In order for aT cellto be activated and produce an immune response, anantigen-presenting cellmust present two signals to the T cell. One of those signals is themajor histocompatibility complex(MHC), combined with the antigen, and the other signal is theCD80orCD86molecule (also known as B7-1 and B7-2). Abatacept binds to the CD80 and CD86 molecule, and prevents the second signal. Without the second signal, the T cell can't be activated.
Abatacept was developed byBristol-Myers Squibband is licensed in the United States for the treatment of rheumatoid arthritis in the case of inadequate response to anti-TNFαtherapy. Abatacept received approval from the FDA in 2005.[4]
Medical uses
[edit]Abatacept is used to treat adults with moderate to severerheumatoid arthritis(RA) as a second-line agent, and as a first-line agent for people whose RA is severe and rapidly progressing. It also used to treatpsoriatic arthritisandjuvenile idiopathic arthritis.[1][5][6][3]
Contraindications
[edit]Abatacept has not been tested in pregnant women and it is not known if it is secreted in breast milk; it causes birth defects in rodents when given in very high doses, and is transmitted in rodent breast milk.[5]
Abatacept will likely interfere with any vaccine given while people are taking it.[5]
It should not be used in combination withanakinraorTNF antagonists.[7]Because abatacept, anakinra, and TNF antagonists suppress the immune system, using them in combination may significantly increase the risk for severe infections.[1]
Adverse effects
[edit]People have experienced serious infections due to abatacept's suppression of the immune system; some of these infections have been fatal. People withCOPDare likely to get lung infections more often than usual. Some people have hadanaphylacticreactions to the drug. Abatacept may cause otherwise slow-growingcancersto proliferate andspread,due to suppression of the immune system.[5]
Very common adverse effects (occurring in more than 10% of people) include upper respiratory tract infections. Common adverse effects (occurring in between 1% and 10% of people) include lower respiratory tract infections, urinary tract infections, herpes infections, pneumonia, flu, cough, high blood pressure, stomach pain, diarrhea, nausea, vomiting, upset stomach, mouth sores,elevated transaminases,rashes, fatigue, weakness, local injection site reactions, and systemic injection reactions.[5]
Chemistry
[edit]Abatacept is afusion proteincomposed of the extracellular domain ofCTLA-4with the hinge, CH2, and CH3 domains ofIgG1.[7]
Mechanism of action
[edit]Abatacept is a soluble CTLA-4 analog that preventsantigen-presenting cells(APCs) from delivering the co-stimulatory signal. This prevents the T cells from beingfully activated,and even downregulates them. Simple signaling without co-stimulation allows the cell to recognize the primary signal as "self" and not ramp-up responses for future responses as well.
In order for T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an APC.
That activation requires two signals (one of which is called co-stimulatory signal or signal 2):
For signal 1, the APC must bind the antigen to amajor histocompatibility complex(MHC) molecule, bring that complex to its surface, and present it to the T cell receptor on the surface of the T cell.
For signal 2, the APC must present a B7 protein (CD80orCD86) on its cell surface to aCD28protein on the surface of the T cell. These two signals activate the T cell. Without signal 2, the T cell will not be activated, and will becomeanergic.
Abatacept, which consists of a fusion protein of the extracellular domain of CTLA-4 and human IgG1, binds to the B7 protein on the APC and prevents it from delivering the co-stimulatory signal to the T cell.[8][9]
References
[edit]- ^abcde"Orencia- abatacept injection, powder, lyophilized, for solution Orencia- abatacept injection, solution".DailyMed.15 December 2021.Retrieved16 March2022.
- ^"FDA approves abatacept for prophylaxis of acute graft".U.S.Food and Drug Administration(FDA).15 December 2021.Archivedfrom the original on 24 January 2022.Retrieved16 March2022.
- ^abcd"Orencia EPAR".European Medicines Agency(EMA).Retrieved6 October2020.
- ^"Drug Approval Package: Orencia (Abatacept) NDA #125118".U.S.Food and Drug Administration(FDA).Retrieved29 December2020.
- ^abcde"UK label prefilled pen".UK Electronic Medicines Compendium. 25 July 2017.
- ^"UK label powder".UK Electronic Medicines Compendium. 25 July 2017.
- ^abMoreland L, Bate G, Kirkpatrick P (2006). "Abatacept".Nature Reviews Drug Discovery.5(3): 185–186.doi:10.1038/nrd1989.PMID16557658.S2CID266176720.
- ^"ABATACEPT & BELATACEPT: the CTLA-4-Igs".Healthvalue.net. Archived fromthe originalon 5 December 2008.Retrieved25 May2007.
- ^Dall'Era M, Davis J (2004). "CTLA4Ig: a novel inhibitor of co-stimulation".Lupus.13(5): 372–376.doi:10.1191/0961203303lu1029oa.PMID15230295.S2CID32235606.
External links
[edit]- "Abatacept".Drug Information Portal.U.S. National Library of Medicine.
