ORENCIA® (abatacept) is the first and only biologic therapy for rheumatoid arthritis (RA) where both ORENCIA® intravenous (IV) and subcutaneous (SC) formulations have been FDA-approved with comparable clinical efficacy and safety profiles.
The dual-route approval provides rheumatologists with flexibility in tailoring treatment based on patient-specific factors.
In this post, let’s look at important distinctions between IV and SC abatacept, discuss proper administration techniques, and outline clinical scenarios in which one route may be preferred over the other.
Key Takeaways
- ORENCIA® is the only biologic therapy for rheumatoid arthritis approved for both IV and SC administration.
- Clinical studies show that IV and SC ORENCIA® offer similar efficacy in treating RA, juvenile idiopathic arthritis, and psoriatic arthritis, with comparable safety profiles.
- IV administration ensures immediate systemic drug exposure, while SC allows at-home treatment with sustained therapeutic effects.
- Route selection depends on disease severity, self-administration ability, access to healthcare facilities, and adherence needs.
What Is ORENCIA® and How Does It Work?
ORENCIA® is a selective T-cell co-stimulation modulator indicated for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, and psoriatic arthritis.
It is composed of a modified human cytotoxic T-lymphocyte antigen-4 (CTLA-4) linked to the Fc region of immunoglobulin G1 (IgG1). It works by binding to the CD80 and CD86 molecules on antigen-presenting cells and preventing their interaction with CD28 on T-cells. This inhibits T-cell activation and the release of pro-inflammatory cytokines.
Specific indications for ORENCIA® include:
- Adults (18+ years) with moderate to severe RA who are unresponsive to other treatments. It can be used alone or with non-biologic disease-modifying antirheumatic drugs (DMARDs), but not with JAK inhibitors or other biologic DMARDs (like TNF blockers like Enbrel®, Humira®, or Remicade®).
- Patients two years and older with polyarticular juvenile idiopathic arthritis alone or in combination with methotrexate.
- Active psoriatic arthritis in patients aged two and older. In adults, it can be used alone or with non-biologic treatments, while in children, it is used alone or with methotrexate. [1]
Routes of Administration of ORENCIA®
ORENCIA® is administered via two routes — IV and SC.
Intravenous Administration
ORENCIA® IV infusion is approved for use in adults and pediatric patients aged six years and above. The IV formulation is not indicated for the treatment of pediatric psoriatic arthritis.
The drug is administered intravenously over a 30-minute period. The initial dose for rheumatoid arthritis patients is 10 mg/kg, followed by 10 mg/kg two and four weeks after the first dose, and then every four weeks thereafter. The IV route ensures rapid and complete absorption with 100% bioavailability.
Here are some details about IV ORENCIA® administration:
- Each vial contains 250 mg of abatacept in powder form for ORENCIA® reconstitution. To prepare the solution, 10 mL of sterile water for injection must be added using the silicone-free disposable syringe provided with the vial and an 18- to 21-gauge needle. Once reconstituted, the abatacept concentration in the vial is 25 mg/mL. [2]
- The solution must be diluted before administration with 0.9% sodium chloride solution (normal saline).
- IV infusion should be delivered through a dedicated line or infusion set with a sterile, non-pyrogenic, low protein-binding filter (0.2 to 1.2 micron pore size).
- The fully diluted ORENCIA® solution must be administered within 24 hours of reconstituting the vials. It can be stored at room temperature or refrigerated at 2°C to 8°C (36°F to 46°F) before use. If not infused within 24 hours, the solution should be discarded. [2]
- Infusion should be monitored for infusion-related reactions (e.g., fever, chills, shortness of breath, and hypotension).
The peak plasma concentration of ORENCIA® administered intravenously is reached at the end of the infusion. The mean half-life is approximately 13 days.
Subcutaneous Administration
ORENCIA® is delivered subcutaneously using either a prefilled syringe or a ClickJect™ Autoinjector. [1]
In pediatric patients with polyarticular juvenile idiopathic arthritis or psoriatic arthritis, self-administration of ORENCIA® can be considered if both the healthcare provider and the parent/legal guardian determine it to be appropriate.
The ORENCIA® subcutaneous dose for rheumatoid arthritis is 125 mg every week. Initial loading doses (day 1, 15, and 30) are given at 125 mg weekly.
The patient should be instructed on how to administer ORENCIA® subcutaneously using the following details:
- ORENCIA® is injected subcutaneously into the thigh or abdomen.
- A 27-gauge needle (recommended) or a 25-gauge needle is used for subcutaneous injections.
- The length of the needle should ideally be 12-16 mm for adults, though longer needles may be required for individuals with more subcutaneous tissue.
- The injection site should be rotated to avoid irritation or tissue damage at a single site.
- Prior to injection, the prefilled syringe or autoinjector should be removed from the refrigerator and allowed to reach room temperature (for approximately 30 minutes) to minimize discomfort.
The peak plasma concentration of the subcutaneously administered drug is reached approximately 3-5 days after administration. The bioavailability is lower than IV administration due to slower absorption from the subcutaneous tissue.
SC vs. IV ORENCIA® — Clinical Efficacy Comparison
In a national multicenter study on 397 patients with rheumatoid arthritis-associated interstitial lung disease, 94 received IV and 303 received SC abatacept, with a median follow-up of 24 months. After adjusting for confounders, both forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) remained stable in both groups during the first 24 months. [3]
Improvement or stability of lung lesions on high-resolution CT was observed in 75% of IV vs. 64% of SC patients. Similarly, dyspnea stabilized or improved in 90% of IV vs. 82% of SC patients.
In another Phase IIIb noninferiority study comparing the clinical efficacy of IV and SC ORENCIA® in patients with an inadequate response to methotrexate, both treatment routes demonstrated similar efficacy. At month six, 76.0% of SC-treated patients and 75.8% of IV-treated patients achieved an ACR20 response. [4]
Other ACR responses (ACR50 and ACR70) over six months were also comparable between both groups. The efficacy results were consistent across various subgroups, including by weight.
Safety Profile and Adverse Effects of IV vs. SC ORENCIA®
The phase IIIb noninferiority study discussed above found that the safety profiles of both routes of administration were comparable. Adverse events occurred in 67.0% of SC-treated patients and 65.2% of IV-treated patients, with serious effects reported in 4.2% and 4.9%, respectively. [4]
Common side effects (≥5% incidence) included headache, nasopharyngitis, upper respiratory tract infection, diarrhea, and nausea. Discontinuations due to serious side effects were 1.1% for SC and 1.9% for IV — they were primarily driven by infections.
No serious infection-related discontinuations occurred in the SC group, while 0.6% of IV-treated patients discontinued treatment due to serious infections. There were two deaths in the SC group (staphylococcal septicemia and an unknown cause) and five deaths due to ORENCIA® IV infusion side effects.
Patient Factors Affecting Route Selection
The decision to administer ORENCIA® via IV infusion or SC injection is based on age, disease severity, ability to self-administer, risk of adverse effects, and access to healthcare facilities.
IV administration is preferred for moderate to severe rheumatoid arthritis or when rapid therapeutic effect is required, as it provides immediate systemic drug exposure with 100% bioavailability. In contrast, SC administration is suitable for stable, long-term disease management, with slightly slower absorption but sustained efficacy.
ORENCIA® IV infusion is also indicated for patients who cannot self-inject due to physical disabilities (e.g., severe arthritis) or cognitive impairment and require adherence through scheduled clinic visits. SC administration allows home-based treatment, provided the patient or caregiver is trained in proper injection techniques.
In addition, ORENCIA® IV is approved for children aged six years and older, while ORENCIA® SC is an option for pediatric polyarticular juvenile idiopathic arthritis and psoriatic arthritis if deemed appropriate by a healthcare provider and legal guardian. However, note that the ability of pediatric patients to self-administer SC injections has not been studied.
FAQs
How Long Does It Take To Infuse ORENCIA®?
ORENCIA® IV infusion takes approximately 30 minutes, though the total clinic visit may be longer due to preparation and monitoring.
How Often Is ORENCIA® IV Dosing?
ORENCIA® IV dosing is administered at weeks zero, two, and four for the initial doses, followed by maintenance infusions every four weeks.
How Soon Does ORENCIA® Work?
The onset of ORENCIA® efficacy varies, but clinical improvement in rheumatoid arthritis is observed within 2-4 weeks, with optimal response seen by 3-6 months.
How Long Does ORENCIA® Infusion Stay In the Body?
ORENCIA® has a terminal half-life of 13-17 days, so it stays in the system for several weeks. Complete clearance of the drug takes up to two months after discontinuation.
Final Words
ORENCIA® IV and subcutaneous offer equally effective and safe treatment for rheumatoid arthritis.
IV infusion provides immediate systemic exposure and is ideal for patients requiring clinical supervision, while subcutaneous injection allows for convenient at-home administration and promotes long-term adherence in stable patients.
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References
- ORENCIA®. ORENCIA® (abatacept) Patient Site. Published 2024. https://www.orencia.com/support-savings/orencia-faqs
- HIGHLIGHTS of PRESCRIBING INFORMATION These Highlights Do Not Include All the Information Needed to Use ORENCIA Safely and Effectively. See Full Prescribing Information for ORENCIA. ORENCIA (Abatacept) for Injection for Intravenous Use Injection, for Subcutaneous Use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125118s171lbl.pdf
- López-Maraver M, Serrano-Combarro A, Atienza-Mateo B, et al. Subcutaneous vs. intravenous abatacept in rheumatoid arthritis-interstitial lung disease. National multicentre study of 397 patients. Seminars in Arthritis and Rheumatism. 2024;68:152517. doi:https://doi.org/10.1016/j.semarthrit.2024.152517
- Genovese MC, Covarrubias A, Leon G, et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis and rheumatism. 2011;63(10):2854-2864. doi:https://doi.org/10.1002/art.30463
