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Abatacept is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the drug used to treat autoimmune diseases like pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis: Rheumatoid arthritis is an autoimmune joint disease causing infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।" data-rx-term="rheumatoid arthritis" data-rx-definition="Rheumatoid arthritis is an autoimmune joint disease causing inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।">rheumatoid arthritis, by interfering with the immune activity of T cells. It is a fusion protein composed of the Fc region of the immunoglobulin IgG1 fused to the extracellular domain of CTLA-4. In order 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 can’t be activated.
Mechanism of action of Abatacept
Abatacept prevents antigen-presenting cells (APCs) from delivering the co-stimulatory signal. This prevents the T cells from being fully 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 antigen-presenting cell (APC). That activation requires two signals (one of which is called the 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. Although there are multiple pathways and cell types involved in the pathogenesis of pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis: Rheumatoid arthritis is an autoimmune joint disease causing infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।" data-rx-term="rheumatoid arthritis" data-rx-definition="Rheumatoid arthritis is an autoimmune joint disease causing inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।">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.
Indications of Abatacept
- Rheumatoid arthritis
- Severe, active rheumatoid arthritis
- Ankylosing spondylitis
- Psoriatic arthritis
- Moderate to severe juvenile idiopathic pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis
- Severe to moderate rheumatoid arthritis
- Plaque Psoriasis
- Psoriasis
- Spondyloarthritis
- Uveitis
Contra-Indications of Abatacept
- Tuberculosis
- Chronic obstructive lung disease
- Infection caused by Blastomyces dermatitidis fungus
- Opportunistic fungal infection
- Pneumonia
- Severe infection
- Infection that lasts a long time
- Malignant melanoma
- Diabetes that is not under control
- The acquired decrease of all cells in the blood
- Low blood counts due to bone marrow failure
- Decreased neutrophils a type of white blood cell
- Multiple sclerosis
- Demyelinating Disease
- Sudden blindness and pain Upon moving the eye
- Heart failure
- Pneumonia caused by Legionella pneumophila bacteria
- Seizures
- Reactivated tuberculosis
- Sepsis syndrome
- Malignant lymphoma
- Relapse of hepatitis B infection symptoms
- Hepatitis B
Dosage of Abatacept
Strengths: 250 mg; 125 mg/mL; 50 mg/0.4 mg/mL
arthritis: Rheumatoid arthritis is an autoimmune joint disease causing inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।" data-rx-term="rheumatoid arthritis" data-rx-definition="Rheumatoid arthritis is an autoimmune joint disease causing inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।">Rheumatoid Arthritis
IV
- Less than 60 kg, give 500 mg
- If 60 to 100 kg, give 750 mg
- If greater than 100 kg, give 1000 mg
- Administer as a 30-minute IV infusion; repeat the dose 2 and 4 weeks after the initial dose, then every 4 weeks thereafter.
Subcutaneous
- 125 mg subcutaneously once a week with or without an IV loading dose
- For patients initiating therapy with an IV loading dose, begin therapy with a single IV infusion followed by the first 125 mg subcutaneous injection administered within a day of the IV infusion.
Psoriatic Arthritis
IV
- Less than 60 kg, give 500 mg
- If 60 to 100 kg, give 750 mg
- If greater than 100 kg, give 1000 mg
- Administer as a 30-minute IV infusion; repeat the dose 2 and 4 weeks after the initial dose, then every 4 weeks thereafter.
Subcutaneous
- 125 mg subcutaneously once a week (without an IV loading dose)
Pediatric Juvenile Idiopathic Arthritis
IV ,6 years and older
- fast breathing
- If less than 75 kg: 10 mg/kg IV
- If 75 kg to 100 kg: 750 mg IV
- If greater than 100 kg: 1000 mg IV
- Maximum dose: 1000 mg
- Administer once as a 30-minute IV infusion; repeat at 2 and 4 weeks after the initial dose, then every 4 weeks thereafter
Subcutaneous
2 years and older; The subcutaneous injection should be given without an IV loading dose
- If 10 kg to less than 25 kg: 50 mg subcutaneously once a week
- If 25 kg to less than 50 kg: 87.5 mg subcutaneously once a week
- If 50 kg or more: 125 mg subcutaneously once a week
Side Effects of Abatacept
The most common
- Nausea and vomiting
- Back pain
- Bladder pain
- multiple sclerosis,
- Severe diarrhea
- Vaginal thrush
- Skin rash redness or itching, pain, or swelling at the injection site
- Headache
- chest pain
- constipation
- cough
- diarrhea or loose stools
- difficulty with breathing
- dizziness
- heartburn
- muscle pain
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- Heartburn
- Indigestion
- headache, severe and throbbing
- joint or back pain
- Loss of energy or weakness
- pain or burning in the throat
- runny or stuffy nose
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- seizures
- abnormal or fast heart rate
- tremors
- weight loss
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
Drug Interactions of Abatacept
Abatacept may interact with the following drugs, supplements, & may change the efficacy of the drug
- adalimumab
- bacillus Calmette-Guérin (BCG)
- belimumab
- canakinumab
- certolizumab pegol
- live vaccines (e.g., measles, mumps, and rubella (MMR), tuberculosis (BCG), yellow fever)
- cyclophosphamide
- denosumab
- fingolimod
- leflunomide
- nivolumab
- natalizumab
- pimecrolimus
- roflumilast
- sulfasalazine
- tacrolimus
- tocilizumab
- tofacitinib
- trastuzumab
- vaccines (e.g., yellow fever, BCG, cholera, typhoid, varicella, meningococcal, diphtheria)
Pregnancy Catagory of Abatacept
FDA Pregnancy Category C
Pregnancy
There have been no studies on the use of abatacept by pregnant women. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if abatacept passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of the intravenous form of abatacept have not been established for children less than 6 years of age. The subcutaneous form of this medication has not been studied for use by children and adolescents. It is not recommended for this age group.
References
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