Abatacept

ORENCIA is a selective T cell costimulation modulator indicated for: • the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). • the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). • the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA). • the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor. Limitations of Use: Concomitant use of ORENCIA with other immunosuppressives [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.

Abatacept, a selective costimulation modulator, inhibits T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. Activated T lymphocytes are implicated in the pathogenesis of RA, pJIA and PsA and are found in the synovium of patients with RA, pJIA and PsA. In vitro, abatacept decreases T-cell proliferation and inhibits the production of the cytokines TNF alpha (TNFα), interferon-γ, and interleukin-2. In a rat collagen-induced arthritis model, abatacept suppresses inflammation, decreases anti-collagen antibody production, and reduces antigen specific production of interferon-γ. The relationship of these biological response markers to the mechanisms by which ORENCIA exerts its clinical effects is unknown.

Intravenous Use for Adult RA and Adult PsA. • Administer at 0, 2, and 4 weeks, and every 4 weeks thereafter, as a 30-minute infusion Body Weight of Patient Dose Number of Vials Less than 60 kg 500 mg 2 60 to 100 kg 750 mg 3 More than 100 kg 1,000 mg 4 Subcutaneous Use for Adult RA. • Prior to the first subcutaneous dose, may administer an optional loading dose as a single intravenous infusion as per body weight categories above. • Administer 125 mg by subcutaneous injection once weekly (within a day of the intravenous infusion if infusion given). • Patients switching from intravenous use to subcutaneous use, administer first subcutaneous dose instead of next scheduled intravenous dose. Intravenous Use for pJIA in Pediatric Patients ≥6 Years Old.

None. None.

• Concomitant use with a TNF antagonist can increase the risk of infections and serious infections. • Hypersensitivity and anaphylaxis have occurred. • Serious infections reported. Patients with a history of recurrent infections or underlying conditions predisposing to infections may experience more infections. Discontinue if a serious infection develops. • Screen for latent TB infection prior to initiating therapy. Patients testing positive should be treated prior to initiating ORENCIA. • Screen for viral hepatitis prior to initiating ORENCIA. • Update vaccinations prior to initiating ORENCIA. Live vaccines should not be given concurrently or within 3 months of discontinuation. ORENCIA may blunt the effectiveness of some immunizations. • COPD patients may develop more frequent respiratory adverse reactions.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors • Hypersensitivity Reactions • Infections • Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD) • Immunosuppression • Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT) • Most common adverse events (≥10%) in RA are headache, upper respiratory tract infection, nasopharyngitis, and nausea. • Most common adverse reactions (≥10%) in prophylaxis of aGVHD are anemia, hypertension, CMV reactivation/CMV infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia, and acute kidney injury.

Immunosuppressants Concomitant administration of a TNF antagonist with ORENCIA has been associated with an increased risk of serious infections and no significant additional efficacy over use of the TNF antagonists alone. Concurrent therapy with ORENCIA and TNF antagonists is not recommended. There is insufficient experience to assess the safety and efficacy of ORENCIA administered concurrently with other biologic RA therapy, such as anakinra, or other biologic PsA therapy, and JAK inhibitors and therefore such use is not recommended.

Refrigerate ORENCIA lyophilized powder supplied in a vial at 2°C to 8°C (36°F to 46°F). Refrigerate ORENCIA solution supplied in a prefilled syringe or ClickJect autoinjector at 2°C to 8°C (36°F to 46°F). Do not allow the prefilled syringe or autoinjector to freeze. Protect from light by storing in the original package until time of use.