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Top 5 things about Abatacept

Abatacept is a special biological drug that blocks the immune system’s T cells. It is an injection given once per week, and it can be used to treat autoimmune diseases in which the immune system attacks healthy tissue. Abatacept has helped many people with rheumatoid arthritis so they are able to function better on a daily basis. Abatacept is also used to treat psoriatic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis.

Abatacept blocks T cells so they cannot cause inflammation in the body. Scientists discovered that if the T cells are blocked, then other immune system cells can fight off and control the symptoms of arthritis. Abatacept does not cure autoimmune diseases, but it can help reduce symptoms and decrease permanent joint damage.

The side effects for this drug are generally mild and include fever, sore throat, nausea or diarrhea. Other side effects may occur such as new psoriasis outbreaks, temporarily low white blood cell count, and a resurgence of the disease you are trying to control. Please consult a doctor before using this drug if you have active tuberculosis, infections, heart failure, certain cancers like leukemia or lymphoma, active psoriasis (red scaly skin patches), if you are pregnant, breastfeeding or plan on becoming pregnant.

The most common side effects experienced by those who take abatacept are fever (low grade), sore throat, nausea/vomiting, diarrhea, headache and lower respiratory tract infection. Because it is an immunosuppressant drug there is always a high risk that the body will develop infections; therefore frequent medical check-ups should be scheduled.

What type of drug is abatacept?

The side effects experienced will vary with each individual, and depending on what medication you are taking it may react negatively with abatacept. If you experience any of the following symptoms after taking abatacept wear a medical alert tag or carry an ID card that states you are on abatacept. You should also consult your doctor right away if any of the following occur: fever over 100 degrees Fahrenheit, severe headache, stiff neck, new skin rashes, eye problems such as blurred vision, pain when urinating or inability to urinate, yellowing of the eyes or skin. Abatacept is not be taken by people who have had an allergic reaction to it in the past.

Abatacept may cause some people to become more likely to develop infections and should not be taken by those with active infection or a history of recurring infections. There is also the risk that abatacept could worsen any current health conditions, including heart failure, certain cancers (such as leukemia, lymphoma), active psoriasis, tuberculosis or other chronic infections. People taking abatacept should tell their doctor if they have or ever had hepatitis B virus infection or are at risk of being infected with HIV.

Abatacept reduces the immune system’s ability to fight off an infection by preventing T cells from becoming active against bacteria, viruses and fungi. Patients who take this drug are therefore at greater risk for developing an infection due to activating T cells not being able to work properly. This medication is known to cause infections such as tuberculosis (TB), and patients that have had infections in the past may reactivate infectious diseases while they are on abatacept.

Abatacept works by preventing certain immune system cells called T-cells from becoming active and producing an inflammatory response in the body which causes inflammation, pain and tissue damage. This drug does this by blocking a molecule called B7-H4 which T cells use to communicate with other cells. Abatacept is injected under the skin once weekly for rheumatoid arthritis and every two weeks for psoriatic arthritis.

Abatacept is FDA approved so it has been proven to be safe and effective for its intended use. It is currently only approved as a treatment for rheumatoid arthritis and psoriatic arthritis however due to the effectiveness of this medication it will soon be used to treat other autoimmune diseases such as ankylosing spondylitis, Crohn’s disease, inflammatory bowel disease (IBD), juvenile rheumatoid arthritis (JRA) and multiple sclerosis.

The risk of developing infections while taking abatacept increases with age; therefore older patients are at greater risk than younger patients. Abatacept works by suppressing T-cells which can increase the body’s susceptibility to serious infections. The FDA has issued warnings about the increased risk of infection from this medication, and it has advised that it should not be used in patients with a history of recurrent infections.

Abatacept is a recombinant fusion protein which consists of the binding portion of CTLA-4 fused to part of human IgG1. It was engineered to bind B7-H4 molecules on T cells only when they are associated with an antigen presenting cell, therefore reducing its affinity for B7-H1 or B7-DC. This reduces the likelihood of undesired effects caused by T cells becoming active against cells from tissues where low level inflammation may be beneficial such as our digestive system. Abatacept binds selectively to antigen presenting cells (APCs) and acts as a signal inhibitor for T-cells. When T-cells are activated against an antigen they produce several signals which lead to inflammation and tissue damage. One of these signals is the binding of B7 molecules on the APC with CD28 receptors on the T-cell, however when abatacept binds to B7 it blocks this signal from occurring.

Abatacept is not completely safe for all patients. The black box warnings that have been issued by the FDA state that use of this drug can increase a patient’s susceptibility to infections including tuberculosis, invasive fungal infections, hepatitis B reactivation in carriers of hepatitis B virus, bacterial sepsis, invasive pneumococcal disease and herpes zoster (shingles).

Patients should be tested for hepatitis B before starting abatacept and those that test positive for the virus should receive the hepatitis vaccine and antiviral therapy as appropriate.

Abatacept was also linked to cardiomyopathy (heart damage) in clinical trials; therefore patients with a history of congestive heart failure or recent myocardial infarction (heart attack) are at greater risk of developing this side effect. Patients currently taking other medications such as prednisone, methotrexate and leflunomide should talk with their doctor about potential drug-drug interactions which could lead to toxicity levels. It has been reported to cause the QTc interval on an electrocardiogram to lengthen, which is a risk factor for arrhythmias such as torsades de pointes (TdP).

THE COMMON ADVERSE EFFECTS ASSOCIATED WITH ABATACEPT THERAPY INCLUDE UPPER RESPIRATORY INFECTIONS, HEADACHE, FATIGUE AND NAUSEA.

The most common adverse effects associated with abatacept therapy include: upper respiratory infections, headache, fatigue and nausea. Abatacept was shown to be less effective in patients that were obese or had hypoalbuminemia (decreased albumin levels) and therefore these individuals should not be treated with this medication. It is important to note that abatacept can increase the risk of cancer progression by stimulating tumor growth however the mechanism by which it does this is currently unknown. Patients have been monitored closely through clinical trials, but increased incidence of nonmelanoma skin cancers including basal cell carcinomas and squamous cell carcinomas has been noted in patients taking abatacept.

The mechanism of action for abatacept is the same as that of CTLA-4 inhibitors such as ipilimumab. It blocks immune checkpoint proteins which are expressed on activated T-cells to prevent the T-cells from interacting with APCs and other T-cells. This leads to a decrease in the activation of T-cells which decreases the production of cytokines such as interferon γ, interleukin 2 and inflammatory molecules such as tumor necrosis factor α (TNF-α). In addition, abatacept prevents upregulation of major histocompatibility complex (MHC) expression on dendritic cells (DCs). As a result, dendritic cell maturation is reduced and antigen presentation to T-cells is decreased. Furthermore, it has been shown that abatacept also blocks the co-stimulation of CD80/CD86 on APCs.

Although CTLA-4 inhibitors have been shown to be effective in a variety of autoimmune diseases, there can also be adverse effects associated with its use. These include pneumonitis, hepatitis and colitis, as well as hypophysitis which is inflammation of the pituitary gland that could lead to adrenal insufficiency or thyroid disease.

However, a recent study by JAMA has shown that abatacept is an effective treatment for rheumatoid arthritis (RA) and could help people who have not been helped by other treatments such as biologics. In addition, it was also noted to be more effective than placebo in these patients.

Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of the joints, can cause deformities over time and significantly reduce a patient’s quality of life. Although this drug has been shown to improve some symptoms of rheumatoid arthritis, it does not directly affect the underlying pathophysiology so therefore it does not cure the disease.

In order to determine the effectiveness of abatacept in people with rheumatoid arthritis, a randomized clinical trial was conducted where 188 patients were either given placebo or one of two different dosage levels of abatacept. These individuals had inadequate responses to treatment with at least one anti-TNF agent and had active disease in spite of treatment with at least one non-steroidal anti-inflammatory drug and/or prednisone, or if they were intolerant of these drugs.

In this study the group receiving the highest dose of abatacept showed statistically significant improvement from baseline in terms of achieving a 20% improvement in the American College of Rheumatology criteria at week 24 compared with placebo. A similar response was seen in the medium dose group although it did not achieve statistical significance. Furthermore, the most common adverse effect reported in this study was an increase in infections which can be attributed to a decrease in T-cells that fight off pathogens.

Is Abatacept a monoclonal antibody?

Abatacept is not a monoclonal antibody. Monoclonal antibodies are developed from a single parent cell line whereas abatacept is a recombinant fusion protein which includes the variable regions of both the human and mouse CTLA4 genes, thus it cannot be considered a monoclonal antibody.

Is Orencia the same as abatacept?

Orencia is the brand name for abatacept whereas abatacept is the generic name. Orencia can only be accessed if prescribed by a doctor which is not the case with abatacept because it is available over-the-counter. Furthermore, Orencia has another active ingredient called palmitate which is not present in abatacept.

Is Orencia the same as CTLA4?

Orencia is not the same as CTLA4 however it has the same mechanism of action. The amino acid sequence for CTLA4 and Orencia are very similar but there are some distinct differences between them.

Does it work the same as Tysabri?

Abatacept and Tysabri both bind to CTLA4 and therefore have a similar mechanism of action. However, they are two distinct drugs that should not be confused with one another.

What is an MHC class II molecule?

MHC class II molecules are found on the surface of cells in order for these cells to present antigens to cytotoxic T-cells.

What is a CD4 molecule?

CD4 is a protein that can be found on the surface of T-cells and binds to the MHC class II antigen.

What is a CD28 molecule?

CD28 is a protein found on the surface of T-cells and works by binding to B7-1 and B7-2 which are proteins that can be found on antigen presenting cells such as macrophages.

Which drugs bind to CTLA4?

There are several drugs that bind to CTLA4 including abatacept, ipilimumab, tremelimumab and ticilimumab. They all have the same mechanism of action which is why they are not recommended for usage in combination with one another. This can cause toxicity within the patient.

What is a CTLA4 molecule?

CTLA4 is a protein that can be found on the surface of T-cells and binds to CD80 and CD86 which are proteins that can be found on antigen presenting cells such as B-cells, macrophages and dendritic cells.

How effective is abatacept?

In one study, abatacept was found to be very effective in individuals with an inadequate response to anti-tumor necrosis factor (TNF) agents.

Is it safe?

In a meta-analysis of 5 randomized clinical trials that involved 718 people who were treated with abatacept and 710 people were treated with placebo or a different drug, serious side effects such as heart attack and pneumonia were rare in both the treatment and placebo groups. However, this study found that infections requiring hospitalization occurred more often among those who received abatacept versus those who did not. In addition to that, it was found that patients who were treated with abatacept had more adverse events such as cough and shortness of breath than those who did not receive the drug.

How does it work?

A study conducted on rats found that when they were injected with antigens, the T-cells in their spleen did not produce cytokine after being exposed to abatacept. In order for the T-cells to be activated, they need a signal from both the CD28 and CTLA4 receptors.

How much does abatacept cost?

Abatacept costs about $1,500 per month.

How is it given?

Abatacept can be administered as an intravenous (IV) infusion or as a subcutaneous injection.

What are the adverse effects of abatacept?

The most common adverse effects of abatacept include upper respiratory infection and fatigue. Other possible side effects include nausea and headache. Less serious side effects that should still be reported to a doctor include: skin rash, swelling in hands and feet and fever.

Is there any interaction between warfarin, dabigatran etexilate and abatacept?

In one case report, a patient was found to experience increased INR when abatacept and warfarin were used together.

Can abatacept be used when breastfeeding?

No information regarding this is available however it should be discussed with your doctor.

The amino acid sequence for CTLA4 and Orencia are very similar but there are some distinct differences between them. It works in a different manner to Tysabri which binds to an e-cadherin found on lymphocytes rather than CTLA4. Abatacept does bind to the receptor CTLA4 but it also has an alternate pathway of action as well, where it inhibits B7 molecules from binding CD28 receptor thus suppressing its activation. This drug has only been approved by the FDA for rheumatoid arthritis and is not recommended for usage in psoriatic arthritis or Crohn’s disease. It is still under investigation for the treatment of ulcerative colitis and ankylosing spondylitis although there are no trials currently enrolling participants.

How do you inject abatacept?

There are many different techniques that can be used when injecting this drug depending on the administration site. The subcutaneous injection is self administered, usually after mixing abatacept with normal saline. Since abatacept is concentrated, it should be drawn into a tuberculin or 1 ml syringe prior to admistering it. When using an IV infusion, the bag of intravenous solution with abatacept should be connected to a 100ml bag of 0.9% sodium chloride for infusions containing 10 mg/kg. A slow intravenous infusion over 3 hours should be done and care must be taken as to not disturb the line during this time as well as afterwards if there is residual within the tubing as this could affect the dose. There are no restrictions on food and drink before or after taking abatacept, however there should be six hours between doses of this drug as it takes 1-3 hours for maximum concentration in the blood to occur.

Is abatacept a biologic?

Yes, it is considered a biological agent as it is manufactured using recombinant DNA technology.

How is it What precautions should you take when taking this drug?

• Avoid women that are or could conceive and breastfeeding and warn your physician if you have had issues with fertility in the past.

• Tell your doctor if you receive blood products as they can affect your immune system which might help with adverse effects during treatment.

• Tell your physician of any allergies you have including to medications or food products.

• You should not receive live vaccines during treatment or after abatacept has been discontinued.

• These are just general guidelines for usage and side effects, speak with your doctor if you have any questions regarding this drug.

What are the precautions when giving an IV infusion of abatacept?

There are no special requirements in terms of fasting or premedicating prior to an IV infusion however it is recommended to run the line slowly in order to avoid initiation of a thrombotic event. An additive must be used in order to prolong the duration of action for this medication when given intravenously as it does not contain additives that do so. Abatacept can be used along with other medications such as abciximab and eptifibatin, however it should not be mixed in the same IV tubing or infusion and there is no need to flush line afterwards as this drug has a half life of 100 minutes.

How does an IV infusion of abatacept work?

It takes one hour for maximum concentration in the bloodstream to occur which peaks at two hours. The effect that this medication has on the body is expected to last for between 24-72 hours after you receive your dose depending on how much was given. This drug is metabolized by esterases and peptidases found in plasma as well as those found in tissues so the half life is estimated to be 100 minutes. The primary mechanism of action for this drug is inhibition of CD28 molecules on T-cells which serves to control the immune response in order to reduce inflammation.

What are the adverse effects that can occur?

• Bloating

• Chills

• Decrease in appetite

• Headache

• Itching

• Muscle aches

• Neck pain or stiffness

• Nausea o Vomiting

What are the common side effects? These include: nausea, vomiting diarrhea, headache, upper respiratory infection, fever and back pain. Other more severe side effects might occur including a fall in white blood cells or platelets as well as severe skin reactions, severe allergic reaction and breathing difficulties.

What is the usual dosage?

The dose for this drug depends on your current health status as well as other medications being taken. For those who have impaired renal function a decreased dose might be required. The recommended dosages are listed below:

• Adults with rheumatoid arthritis

– A single intravenous infusion of 10 mg/kg once every four weeks or 7.5 mg/kg twice weekly .

• Adults with psoriatic arthritis

– A single intravenous infusion of 10 mg/kg once every four weeks .

• Adult patients with active psoriatic arthritis who have had an inadequate response to methotrexate

– A single intravenous infusion of 10 mg/kg once every four weeks.

What is the common dosage? The usual dose is 10mg/kg as a one time IV infusion which should be given every 4 weeks.

When do you know if abatacept is working? You will know that the medication has been effective as your symptoms such as joint pain, swelling and tenderness will be reduced.

How long does it take for the medication to work? It takes 1-3 hours for maximum concentration in the blood to occur which peaks at two hours. The effect that this drug has on your body should last for 24-72 hours.

What other medications can you not take while on abatacept? This drug should not be taken if you are allergic to it or any of its components, due to the risk of developing a life threatening reaction. Abatacept is considered unsafe during pregnancy and lactation and should be avoided unless the benefits outweigh the risks. It is unknown whether this medication passes into breast milk therefore it is recommended to avoid breastfeeding two weeks after receiving treatment.

Is there anything else I need to know regarding abatacept? Abatacept should not be used in patients who have had an organ transplant as it may cause harm or rejection. Immunizations such as live vaccines should not be given while on this drug as it can decrease your response to them. The use of abatacept is also not recommended for those with severely weakened immune systems or bone marrow function problems, or patients who are experiencing an infection.

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