Abatacept (Orencia) is a novel drug recently approved in the United States and European countries for the treatment of autoimmune rheumatic diseases like Rheumatoid Arthritis.

Abatacept drug class:

It belongs to the class of medicine that inhibits the activation of T cells by binding to CD 80 and CD 86 present on the APC (antigen-presenting cells). It is a selective costimulation modulator

(Abatacept) Orencia indications:

• It may be used as a monotherapy or in combination with other anti-rheumatic drugs in patients  Rheumatoid arthritis.
• Abatacept should not be used along with TNF-blocking agents (like adalimumab, etanercept, and infliximab, etc) and anakinra.
• It can also be used alone or in conjunction with methotrexate to treat mild to severe juvenile idiopathic arthritis.

Abatacept in Psoriatic arthritis:

• The FDA has approved abatacept for treating psoriatic arthritis. NSAIDs, Methotrexate, Sulfasalazine, cyclosporin, and leflunomide are effective in the treating peripheral arthritis in patients with psoriasis.
• However, none of these drugs have proven roles in modifying disease progression and halting joint destruction.
• Abatacept in clinical trials was found effective in 39% of the patients compared to placebo (22%).
• It has also been found effective in patients with axial involvement in psoriatic arthritis, enthesitis, and dactylitis. 

Abatacept in Juvenile idiopathic arthritis:

• Additionally, it has been licenced for use in children with moderately to highly active juvenile idiopathic arthritis as a monotherapy or in combination with methotrexate.

(Abatacept) Orencia dose:

Abatacept (Orencia) should be administered via an intravenous infusion initially

Adult patients with upto 60 kg body weight:

Dose via intravenous infusion:

• 3 doses of 500 mg every 15 days
• 500 mg every month by intravenous infusion

Otherwise it can be infused by a subcutaneous injection:

• 125 mg once a week, with the first dosage administered subcutaneously one day after the intravenous loading dose;
• Patients who are unable to get an intravenous infusion may begin subcutaneous abatacept treatment without first receiving an intravenous loading dose.

Adult patients with a body-weight of 60 – 100 kgs:

• A Loading Dose via an intravenous infusion:
  • 750 mg every 15 days for 3 doses
  • followed by intravenous infusions 750 mg monthly.

Alternatively by subcutaneous injection:

• 125 mg once weekly, the first subcutaneous dose should be given within 1 day of the intravenous loading dose;
• (patients who are unable to receive an infusion may initiate subcutaneous abatacept without receiving an intravenous loading dose)

101 kg and above weighing adults:

Loading dose via intravenous infusion: 3 doses of 1000mg for 15 days 

• 1000 mg every month by intravenous infusion

Alternatively by subcutaneous injection:

• The first subcutaneous dose of 125 mg once weekly should be administered one day after the intravenous loading dose; 
• (patients who are unable to receive an infusion may initiate subcutaneous abatacept without receiving an intravenous loading dose).

Intravenous Dose of Orencia (Abatacept) in Children:

Children 6 years of age or older and weighing less than 75 kgs:

• 10 mg/kg
• The dose is repeated at 2 weeks and 4 weeks after the initial dose and every 4 weeks thereafter

Children 6 years or older and weighing more than 75 kgs:

• Follow the Usual adult dosing with a maximum dose of up to 1000 mg
• Following the initial dose, the dose is repeated at 2 weeks, 4 weeks, and then every 4 weeks after that. 

Dose in Kidney disease:

• The manufacturer has not provided any dose adjustment in patients with kidney disease. 

Dose in Liver Disease:

• The manufacturer has not provided any dose adjustment in patients with liver disease.

How to administer Abatacept (Orencia)?

Intravenous infusion of Orencia:

• Infuse for 30 minutes.
• Inject using 0.2-1.2 micron low protein-binding filter

Subcutaneous administration of Orencia:

• Before injecting, let the prefilled syringe warm at room temperature for 30 to 60 minutes.
• Preferably inject into front thigh, or the abdomen but not close to the navel (keep a distance of about three fingers from the navel), or the outer upper arms (the least preferred site).
• Do not inject into an inflamed area i.e. tender, bruised, red, or hard skin.
• Always rotate the injection sites

Pregnancy Risk Category: C

It may be used if benefits outweigh the risks

• Pregnancy Implications  Pregnant females have not been tested with Abatacept. Animal studies have not shown any teratogenic effects.
• Lactation It is not known if abatacept is found in breast milk.

Considerations for Breastfeeding

• Breastfeeding is not recommended due to the adverse effects on the developing immune system

Side effects of Abatacept:

Abatacept is contraindicated in patients allergic to it, HIV, and immunocompromised patients who are at risk of infection and sepsis.

• Hypersensitivity reactions:

  • Hypersensitivity reactions may involve anaphylactic reactions resulting in hypotension that may occur during the infusion and within 24 hours of the infusion.
  • Epinephrine, fluids, and steroids must be available while infusing the medicine.

• Infections:

  • Patients are also at risk of developing serious infections such as the reactivation of tuberculosis, pneumocystis pneumonia, and other bacterial and viral infections.
  • Screening must be done for hepatitis B infections and immunized prior to initiating the treatment in patients. 

• Malignancies:

  • The risks of malignancies such as lymphoma and lung cancer have been associated with its use.
  • However, these cancers are more common in patients with rheumatoid arthritis and the data is scarce regarding the associations of cancers with abatacept use.

Common side effects of Abatacept (Orencia): 

• Abdominal pain
• Vomiting
• Nausea
• Flushing
• Conjunctivitis
• Infection
• Cough
• Stomatitis
• Fatigue 
• Paraesthesia
• Headache
• Diarrhea
• Pain in extremities
• Dizziness
• Hypertension
• Dyspepsia
• Fatigue

Uncommon adverse effects of Orencia:

• Psoriasis
• Weight gain
• Dyspnoea
• Gastritis
• Palpitation
• Alopecia
• Bradycardia
• Hypotension
• Anxiety
• Dry eye
• Visual disturbance
• Tachycardia
• Arthralgia
• Thrombocytopenia
• Basal and squamous cell carcinoma
• Dry skin
• Skin papilloma
• Depression 
• Bronchospasm
• Hypertension
• Sleep disorder
• Bruising
• Depression
• Hyperhidrosis
• Menstrual disturbances

Rare side effects of Abatacept:​​​​​​​

• Lung cancer
• lymphoma

Mechanism of Action (MOA) of Orencia (Abatacept):

• The drug abatacept modulates costimulation. It binds to CD80 on antigen-presenting cells to prevent T-cell (T-lymphocyte) activation (APC).

• This prevents the necessary CD28 interaction between T cells and APCs. T cells that have been activated are present in the synovium of rheumatoid arthritis patients.

Pharmacodynamics/Kinetics of Orencia:

• Half-life elimination: 8-25 days

Monitoring Parameters

• Signs and symptoms that indicate infection. It is recommended that you screen for TB and hepatitis before starting therapy.

International Brand Names of Abatacept:

• Orencia

Currently, it is not available in Pakistan. 

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