ORENCIA (Abatacept)

What Is ORENCIA and What Is It Used For?

ORENCIA contains the active substance abatacept, a protein produced through cell culture technology. It belongs to a class of medications known as selective T-cell co-stimulation modulators, which represent a targeted approach to managing autoimmune joint diseases. Unlike conventional immunosuppressants that broadly suppress the immune system, abatacept works by selectively interfering with the activation of specific immune cells called T-cells that play a central role in the inflammatory cascade underlying rheumatoid arthritis and psoriatic arthritis.

The mechanism of action of abatacept involves binding to CD80 and CD86 molecules on the surface of antigen-presenting cells. This binding prevents these molecules from interacting with the CD28 receptor on T-cells, effectively blocking the co-stimulatory signal required for full T-cell activation. By disrupting this activation pathway, ORENCIA reduces the production of pro-inflammatory cytokines and slows the cascade of immune events that lead to joint inflammation and destruction.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a progressive, chronic, systemic autoimmune disease that, if left untreated, can lead to severe consequences including joint destruction, increasing disability, and significantly reduced ability to perform everyday activities. In individuals with RA, the body's own immune system attacks normal tissue, leading to pain, swelling, and stiffness in the joints. Over time, this persistent inflammation erodes cartilage and bone within the joint, causing irreversible structural damage.

RA affects each individual differently. In most patients, joint symptoms worsen gradually over several years. However, in some cases, RA can progress rapidly with accelerated joint damage, while in others, symptoms may appear for a limited period before improving. Regardless of the clinical pattern, RA is typically a chronic disease that worsens over time, meaning that even with treatment, joint damage may continue to progress if the disease is not adequately controlled.

ORENCIA is approved for the treatment of moderate to severe active rheumatoid arthritis in adults who have not responded adequately to treatment with other disease-modifying antirheumatic drugs (DMARDs) or a class of medications called tumour necrosis factor (TNF) inhibitors. It is used in combination with methotrexate. Additionally, ORENCIA can be used with methotrexate for the treatment of highly active and progressive RA that has not been previously treated with methotrexate. The clinical goals of ORENCIA therapy include slowing joint damage progression, improving physical function, and reducing pain and fatigue to improve overall quality of life.

Psoriatic Arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints that typically occurs in association with psoriasis, an inflammatory skin condition. PsA can affect any joint in the body and may cause pain, swelling, stiffness, and reduced range of motion. If left untreated, PsA can lead to permanent joint damage and disability.

For patients with active psoriatic arthritis, ORENCIA is used when other medications have not provided sufficient disease control. The treatment goals include reducing signs and symptoms of the disease, slowing bone and joint damage, and improving physical function and the ability to perform normal daily activities. ORENCIA can be used alone or in combination with methotrexate for the treatment of PsA.

What Should You Know Before Taking ORENCIA?

Contraindications

Warnings and Precautions

Before and during treatment with ORENCIA, it is essential to communicate openly with your healthcare team about your medical history and any changes in your health. Several important safety considerations apply to patients receiving abatacept therapy.

Allergic reactions: If you experience chest tightness, wheezing, severe dizziness or lightheadedness, swelling, or skin rash during or after an injection, contact your doctor immediately. Serious allergic reactions, including anaphylaxis, have been reported with abatacept use, although they are uncommon.

Infections: ORENCIA may impair the body's ability to fight infections. Tell your doctor if you have any type of infection, including chronic or localised infections, if you frequently develop infections, or if you have symptoms of infection such as fever, malaise, or dental problems. Patients on abatacept therapy may be more susceptible to developing new infections or worsening existing ones. Serious infections, including sepsis and pneumonia, have been reported in clinical trials.

Tuberculosis (TB): Before starting ORENCIA, you will be screened for tuberculosis through a skin test or blood test. If you have a history of TB or symptoms suggestive of TB (persistent cough, weight loss, lethargy, mild fever), inform your doctor. Latent tuberculosis must be treated before initiating abatacept therapy, as the medication may increase the risk of TB reactivation.

Viral hepatitis: Your doctor will screen for hepatitis before prescribing ORENCIA, as the medication may affect the course of viral hepatitis infections.

Progressive Multifocal Leukoencephalopathy (PML): If you, your partner, or your caregiver notice new or worsening neurological symptoms including generalised muscle weakness, vision disturbances, difficulty speaking, changes in gait or balance, or changes in thinking, memory, or orientation leading to confusion and personality changes, contact your doctor immediately. These may be symptoms of PML, a very rare, serious, and potentially fatal brain infection.

Cancer: If you have cancer, your doctor will determine whether you can still receive ORENCIA. The potential role of abatacept in the development of malignancies is not fully established, but cases of skin cancer and lymphoma have been reported in patients receiving the medication.

Vaccinations: Certain vaccines should not be given during treatment with ORENCIA. Live vaccines in particular should be avoided, as they may cause infections in immunocompromised patients. Discuss any planned vaccinations with your doctor before receiving them. If you received ORENCIA during pregnancy, your infant may be at increased risk of vaccine-related infections for up to approximately 14 weeks after your last dose.

Children and Adolescents

ORENCIA solution for injection in a pre-filled pen (ClickJect) has not been studied in children and adolescents under 18 years of age and is therefore not recommended for this patient group. ORENCIA powder for concentrate for solution for infusion is available for paediatric patients aged 6 years and older, and ORENCIA solution for injection in a pre-filled syringe is available for paediatric patients aged 2 years and older.

Drug Interactions

ORENCIA should not be used together with other biologic medicines for rheumatoid arthritis, including TNF inhibitors such as adalimumab, etanercept, and infliximab. There is insufficient data to recommend concurrent use with anakinra or rituximab. However, ORENCIA can be used alongside other commonly used RA medications, including corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac, and conventional DMARDs such as methotrexate.

Pregnancy and Breastfeeding

The effects of ORENCIA during pregnancy are not fully known. Do not use ORENCIA if you are pregnant unless your doctor specifically recommends it. Women of childbearing potential must use effective contraception during treatment and for up to 14 weeks after the last dose. If you become pregnant while using ORENCIA, inform your doctor immediately.

If you received ORENCIA during pregnancy, your infant may have an increased risk of vaccine-related infections. It is important to inform your infant's healthcare providers about your use of ORENCIA during pregnancy so they can determine the appropriate vaccination schedule.

It is not known whether ORENCIA is excreted in breast milk. You must discontinue breastfeeding if you are being treated with ORENCIA and should not breastfeed for up to 14 weeks after the last dose.

Driving and Operating Machinery

ORENCIA is not expected to affect the ability to drive or operate machinery. However, if you feel tired or unwell after receiving ORENCIA, you should not drive or operate machinery until you feel better.

How Does ORENCIA Interact with Other Drugs?

Understanding drug interactions is critical for the safe and effective use of ORENCIA. As a biologic immunomodulator, abatacept interacts with the immune system in ways that can be amplified or complicated when combined with certain other medications. The following table summarises the key interactions that patients and healthcare providers should be aware of.

Major Interactions

The most clinically significant interactions involve the combination of ORENCIA with other biologic immunomodulators. Clinical studies have demonstrated that combining abatacept with TNF inhibitors does not provide additional therapeutic benefit compared to using either agent alone, while significantly increasing the risk of serious infections and other adverse events. The American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) guidelines explicitly recommend against combining biologic DMARDs.

Live vaccines pose a particular concern because ORENCIA modulates the immune response, potentially allowing attenuated vaccine organisms to cause active infection. This risk extends to infants born to mothers who received ORENCIA during pregnancy, as abatacept may cross the placenta and affect the infant's immune response for up to 14 weeks after the mother's last dose.

Minor Interactions

Inactivated vaccines can generally be administered during ORENCIA treatment, although the immune response may be somewhat reduced. It is advisable to ensure that all recommended vaccinations, particularly influenza and pneumococcal vaccines, are up to date before initiating abatacept therapy. Blood glucose monitoring devices that use test strips containing maltose may give falsely elevated readings on the day of intravenous abatacept infusion, as the IV formulation contains maltose. This does not apply to the subcutaneous formulation.

What Is the Correct Dosage of ORENCIA?

ORENCIA solution for injection is administered subcutaneously (under the skin) using a pre-filled pen called ClickJect. Always use this medicine exactly as your doctor or pharmacist has instructed. The dosing regimen is designed to maintain consistent therapeutic drug levels and provide sustained immune modulation throughout the course of treatment.

Adults

Children

Elderly

Missed Dose

It is very important to use ORENCIA exactly as prescribed by your doctor. If you miss a dose:

• Within 3 days of the scheduled dose: Take your dose as soon as possible, then resume your regular weekly schedule on your usual day.
• More than 3 days after the scheduled dose: Consult your doctor about when to take your next dose.

Maintaining a regular injection schedule is important for achieving optimal disease control. Consider setting a weekly reminder to help you remember your injection day.

Overdose

If you accidentally use more ORENCIA than prescribed, contact your doctor immediately. Your doctor will monitor you for any signs or symptoms of adverse effects and provide appropriate treatment if necessary. In clinical trials, doses up to approximately 50 mg/kg intravenously were administered without apparent dose-limiting toxicity. However, any suspected overdose should be evaluated by a healthcare professional.

Stopping Treatment

Do not stop using ORENCIA without discussing it with your doctor first. Discontinuing treatment without medical guidance may lead to a flare of your disease. Your doctor will advise you on the appropriate duration of treatment based on your individual response and disease activity.

What Are the Side Effects of ORENCIA?

Like all medicines, ORENCIA can cause side effects, although not everybody gets them. The side effects observed in clinical trials of abatacept range from very common, mild events to rare, serious adverse reactions. Understanding the frequency and nature of these side effects helps patients and healthcare providers make informed treatment decisions and recognise potential complications early.

The overall safety profile of abatacept has been established through extensive clinical trial programmes involving thousands of patients followed over multiple years. Post-marketing surveillance continues to monitor for additional safety signals. If you notice any side effects not listed here, or if any side effects become serious, tell your doctor, pharmacist, or nurse.

How Should You Store ORENCIA?

Proper storage of ORENCIA is essential to maintain the medication's effectiveness and safety. As a biologic medicine, abatacept is a protein-based product that can be degraded by improper temperature conditions, light exposure, or physical agitation.

• Refrigerate: Store at 2°C to 8°C (36°F to 46°F) in a refrigerator.
• Do not freeze: Freezing can damage the protein structure and render the medication ineffective.
• Protect from light: Keep the pre-filled pens in their original packaging until ready for use.
• Before injection: Remove one pen from the refrigerator and allow it to reach room temperature (approximately 25°C / 77°F) for 30 minutes. Do not remove the needle cap while the pen is warming up.
• Check before use: Inspect the solution through the viewing window. It should be clear to slightly yellow. Do not use if the liquid is cloudy, discoloured, or contains large particles.
• Check expiry date: Do not use after the expiration date printed on the label and carton.
• Keep out of reach of children.

Do not dispose of medicines in wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. Used pre-filled pens should be placed in a sharps disposal container immediately after use.

What Does ORENCIA Contain?

Understanding the composition of ORENCIA is important for patients who may have allergies or sensitivities to specific ingredients. The formulation has been designed to maintain the stability and bioavailability of the abatacept protein.

Active Ingredient

Each pre-filled pen contains 125 mg of abatacept, a fusion protein consisting of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1). It is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells.

Inactive Ingredients (Excipients)

• Sucrose (stabiliser)
• Poloxamer 188 (surfactant)
• Monobasic sodium phosphate monohydrate (buffer)
• Dibasic sodium phosphate anhydrous (buffer)
• Water for injections (solvent)

This medicine contains less than 1 mmol (23 mg) sodium per dose, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.

Appearance and Packaging

ORENCIA solution for injection is a clear, colourless to slightly yellow solution supplied in a pre-filled pen called ClickJect. ORENCIA is available in packs of 4 pre-filled pens and multipacks of 12 pre-filled pens (3 packs of 4). Not all pack sizes may be marketed in all countries.

The ClickJect pre-filled pen is designed for single use only. It features an automatic injection mechanism, a transparent tip that locks over the needle after injection is complete, and a viewing window to verify that the full dose has been delivered.

How Do You Use the ORENCIA ClickJect Pen?

The ORENCIA ClickJect pre-filled pen is designed for ease of use and allows patients to self-administer their weekly injection at home after appropriate training by a healthcare professional. Before using the pen for the first time, ensure that your doctor or nurse has demonstrated the correct injection technique.

Step 1: Prepare Your ClickJect Pen

• Remove one pen from the refrigerator and let it sit at room temperature (approximately 25°C) for 30 minutes.
• Do not remove the needle cap while the pen is warming up.
• Wash your hands thoroughly with soap and water.
• Check the expiry date on the label – do not use if expired.
• Inspect the pen for any damage – do not use if cracked or broken.
• Check the solution through the viewing window – it should be clear to slightly yellow. A small air bubble is normal and does not need to be removed.

Step 2: Prepare the Injection Site

• Choose an injection site on the abdomen or front of the thigh.
• You may use the same body area each week, but choose different injection sites within that area.
• Do not inject into skin that is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks.
• Clean the injection site with an alcohol swab and allow it to dry.
• Pull the orange needle cap straight out. Do not twist. Do not replace the cap once removed.

Step 3: Inject the Dose

• Hold the pen so you can see the viewing window, at a 90-degree angle to the injection site.
• Gently pinch the cleaned skin with your other hand.
• Press down into the skin to unlock the pen.
• Press the button, hold for 15 seconds, and watch the viewing window.
• You will hear a click when the injection begins.
• Wait until the blue indicator stops moving in the window to confirm the full dose has been delivered.
• Remove the pen by lifting it straight up. The transparent tip will automatically lock over the needle.

Step 4: After Injection

• There may be slight bleeding – hold a cotton ball or gauze on the site if needed.
• Do not rub the injection site.
• Cover with a small adhesive bandage if desired.
• Immediately dispose of the used pen in a sharps disposal container.
• Do not replace the cap on a used pen.
• Keep the sharps container and pens out of reach of children.
• Record the date, time, and injection site for your records.

References

1. European Medicines Agency (EMA). ORENCIA (abatacept) – Summary of Product Characteristics. Last updated 2024. Available at: EMA EPAR – ORENCIA.
2. U.S. Food and Drug Administration (FDA). ORENCIA (abatacept) – Prescribing Information. Bristol-Myers Squibb. Available at: FDA Label – ORENCIA.
3. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Annals of the Rheumatic Diseases. 2023;82(1):3-18.
4. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care & Research. 2021;73(7):924-939.
5. Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. New England Journal of Medicine. 2005;353(11):1114-1123.
6. Weinblatt ME, Schiff M, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis. Arthritis & Rheumatism. 2013;65(1):28-38.
7. World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: World Health Organization; 2023.
8. Mease PJ, Gottlieb AB, van der Heijde D, et al. Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis. Annals of the Rheumatic Diseases. 2017;76(9):1550-1558.

Medical Editorial Team