Abatacept (Orencia)

Indicated for rheumatoid arthritis.


Abatacept is a medication used to treat autoimmune diseases like rheumatoid arthritis, by interfering with the immune activity of T cells.



Brand name Orencia.



It is a modified antibody.



Pregnancy category AU: C



Routes of administration: Intravenous, subcutaneous

Binds to and inhibits T-cell activity and can benefit some patients unresponsive to treatments that inhibit TNF-?.

CTLA-4-Ig is an inhibitor of the T-cell costimulatory molecule B7-1 (CD80).


Elimination half-life 13.1 days



It  is a fusion protein composed of the Fc region of the immunoglobulin IgG1 fused to the extracellular domain of CTLA-4. 



For a T cell to be activated and produce an immune response, an antigen-presenting cell must present two signals to the T cell: One of those signals is the major histocompatibility complex (MHC), combined with the antigen, and the other signal is the CD80 or CD86 molecule (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 is not able to be activated.



It is used to treat adults with moderate to severe rheumatoid arthritis as a second line agent, and as a first line agent for people whose RA is severe and rapidly progressing. 



It also used to treat psoriatic arthritis and juvenile idiopathic arthritis.



It has not been tested in pregnant women and it is not known if it is secreted in breast milk



Patients  should be tested for tuberculosis before starting abatacept, and vaccines should be updated prior to starting the drug.



It will likely interfere with any vaccine given while people are taking it.



If used in combination with anakinra or TNF antagonists may significantly increase the risk for severe infections.



Serious infections due to abatacept’s suppression of the immune system may occur, and some of these infections have been fatal. 



It increase  infections in patients with COPD.



IT may cause otherwise slow-growing cancers to proliferate and spread, due to suppression of the immune system.



Adverse effects include: upper respiratory tract infections, 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.



It prevents antigen-presenting cells (APCs) from delivering the co-stimulatory signal. 



Abatacept prevents the T cells from being fully activated, and even downregulates them. 



Without co-stimulation signaling  allows the cell to recognize the primary signal as self and not ramp-up responses for future responses as well.



For T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an antigen-presenting cell (APC).



Such 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 a major 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 on its cell surface to a CD28 protein 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 become anergic.



Abatacept 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.



It is a fusion protein composed of the extracellular domain of CTLA-4 with the hinge, CH2, and CH3 domains of IgG1.



The addition of T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based graft-vs-host disease prophylaxis resulted in reduced rates of acute graft-vs-host disease in patients with hematologic malignancies receiving unrelated donor hematopoietic cell transplantation (HCT).



Adding abatacept to unrelated donor HCT was safe, reduced acute graft-vs-host disease, and improved severe graft-vs-host disease-free survival. 



At a median follow-up of 716 days, the rates of grade 3-4 acute graft-vs-host disease at day 100 were 6.8% in the abatacept group vs 14.8% in the control group.



Rates of grade 2-4 acute graft-vs-host disease were 44.8% vs 63.7%.HR =



Severe graft-vs-host disease-free survival at day 180 was 93.2% vs 82%.



Rates of mild/severe chronic graft-vs-host disease at 1 year were 51.9% vs 45.3.



 No significant differences between groups were observed in 2-year rates of relapse, relapse-free survival, nonrelapse mortality, or overall survival.



Median follow-up was 708 days in the 7/8 patient cohort. Rates of grade 3 to 4 acute graft-vs-host disease at day 100 were 2.3% in the abatacept group compared with 30.2% in the matched CIBMTR cohort.



Rates of grade 2 to 4 acute graft-vs-host disease were 41.9% vs 53.2%.



Severe graft-vs-host disease-free survival at day 180 was 97.7% vs 58.7%.



Flow cytometric analysis showed significant preservation of relative proportions of naive CD4-positive T cells during hematologic reconstitution.



Adding abatacept to unrelated donor HCT was safe, reduced acute graft-vs-host disease, and improved severe graft-vs-host disease-free survival. 



These results suggest that abatacept may substantially improve acute graft-vs-host disease�related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.



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