ORENCIA Dailymed

10 Overdosage

ORENCIA doses up to 50 mg/kg (5 times the maximum recommended dose in patients aged 6 years and older and 3.3 times the maximum recommended dose in patients aged 2 to less than 6 years) have been administered intravenously without apparent toxic effect. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.

11 Description

Abatacept is a selective T-cell costimulation modulator. Abatacept is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Abatacept is produced by recombinant DNA technology in a mammalian cell expression system. The apparent molecular weight of abatacept is 92 kilodaltons.

ORENCIA (abatacept) for injection is a sterile, white, preservative-free lyophilized powder for reconstitution and dilution prior to intravenous infusion. Following reconstitution of the lyophilized powder with 10 mL of Sterile Water for Injection, USP, the reconstituted solution of ORENCIA is clear, colorless to pale yellow, with a concentration of 25 mg/mL and with a pH range of 7.2 to 7.8. Each single-dose vial of ORENCIA provides 250 mg abatacept, maltose (500 mg), monobasic sodium phosphate (17.2 mg), and sodium chloride (14.6 mg).

ORENCIA (abatacept) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale-yellow solution with a pH range of 6.8 to 7.4 for subcutaneous administration. ORENCIA injection is supplied as a single-dose prefilled syringe or as a single-dose ClickJect autoinjector (see Table 6).

Table 6:     Contents of ORENCIA Subcutaneous Injection

Presentation	Active Ingredient Quantity and Volume	Inactive Ingredient Content
ORENCIA injection 50 mg/0.4 mL prefilled syringe	50 mg of abatacept in 0.4 mL of solution	dibasic sodium phosphate anhydrous (0.335 mg) monobasic sodium phosphate monohydrate (0.114 mg) poloxamer 188 (3.2 mg) sucrose (68 mg) qs to 0.4 mL Water for Injection, USP
ORENCIA injection 87.5 mg/0.7 mL prefilled syringe	87.5 mg of abatacept in 0.7 mL of solution	dibasic sodium phosphate anhydrous (0.587 mg) monobasic sodium phosphate monohydrate (0.200 mg) poloxamer 188 (5.6 mg) sucrose (119 mg) qs to 0.7 mL Water for Injection, USP
ORENCIA injection 125 mg/mL prefilled syringe and ClickJect autoinjector	125 mg of abatacept in 1 mL of solution	dibasic sodium phosphate anhydrous (0.838 mg) monobasic sodium phosphate monohydrate (0.286 mg) poloxamer 188 (8 mg) sucrose (170 mg) qs to 1 mL Water for Injection, USP

Unlike the lyophilized formulation for intravenous use, the ORENCIA solutions for subcutaneous administration contain no maltose.

12 Clinical Pharmacology

12.1 Mechanism of Action

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.

12.2 Pharmacodynamics

In clinical trials with ORENCIA at doses approximating 10 mg/kg, decreases were observed in serum levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), rheumatoid factor (RF), C-reactive protein (CRP), matrix metalloproteinase-3 (MMP3), and TNFα. The relationship of these biological response markers to the mechanisms by which ORENCIA exerts its clinical effects is unknown.

No formal pharmacodynamic analyses of biologic response markers have been performed in patients exposed to ORENCIA as prophylaxis for aGVHD.

12.3 Pharmacokinetics

The pharmacokinetics of abatacept were studied in healthy adult subjects after a single 10 mg/kg intravenous infusion and in RA patients after multiple 10 mg/kg intravenous infusions of ORENCIA (see Table 7).

Table 7:     Pharmacokinetic Parameters (Mean, Range) in Healthy Subjects and RA Patients After 10 mg/kg ORENCIA Intravenous Infusion(s)

PK Parameter	Healthy Subjects (After 10 mg/kg Single Dose) n=13	RA Patients (After 10 mg/kg Multiple Dosesa) n=14
a  Multiple intravenous infusions of ORENCIA were administered at days 1, 15, 30, and monthly thereafter.
Peak Concentration (Cmax) [mcg/mL]	292 (175-427)	295 (171-398)
Terminal half-life (t1/2) [days]	16.7 (12-23)	13.1 (8-25)
Systemic clearance (CL) [mL/h/kg]	0.23 (0.16-0.30)	0.22 (0.13-0.47)
Volume of distribution (Vss) [L/kg]	0.09 (0.06-0.13)	0.07 (0.02-0.13)

The pharmacokinetics of abatacept in RA patients and healthy subjects appeared to be comparable. In RA patients, after multiple intravenous infusions, the pharmacokinetics of abatacept showed proportional increases of C_max and AUC over the dose range of 2 mg/kg to 10 mg/kg. At 10 mg/kg, serum concentration appeared to reach a steady state by day 60 with a mean (range) trough concentration of 24 mcg/mL (1 to 66 mcg/mL). No systemic accumulation of abatacept occurred upon continued repeated treatment with 10 mg/kg at monthly intervals in RA patients.

Population pharmacokinetic analyses in RA patients revealed that there was a trend toward higher clearance of abatacept with increasing body weight. Age and gender (when corrected for body weight) did not affect clearance. Concomitant methotrexate, NSAIDs, corticosteroids, and TNF antagonists did not influence abatacept clearance.

No formal studies were conducted to examine the effects of either renal or hepatic impairment on the pharmacokinetics of abatacept.

Abatacept exhibited linear pharmacokinetics following subcutaneous administration. The mean (range) for C_min and C_max at steady state observed after 85 days of treatment was 32.5 mcg/mL (6.6 to 113.8 mcg/mL) and 48.1 mcg/mL (9.8 to 132.4 mcg/mL), respectively. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration was 79%. Mean estimates for systemic clearance (0.28 mL/h/kg), volume of distribution (0.11 L/kg), and terminal half-life (14.3 days) were comparable between subcutaneous and intravenous administration.

Study SC-2 was conducted to determine the effect of subcutaneous monotherapy use of ORENCIA on immunogenicity (without an intravenous loading dose) in 100 RA patients [see Adverse Reactions (6.3)]. In this study, a mean trough concentration of 12.6 mcg/mL was achieved after 2 weeks of dosing.

Consistent with the intravenous data, population pharmacokinetic analyses for subcutaneous ORENCIA in RA patients revealed that there was a trend toward higher clearance of abatacept with increasing body weight [see Dosage and Administration (2.1)]. Age and gender (when corrected for body weight) did not affect apparent clearance. Concomitant medication, such as methotrexate, corticosteroids, and NSAIDs, did not influence abatacept apparent clearance.

In Study JIA-1 among patients 6 to 17 years of age, the mean (range) steady state serum peak and trough concentrations of abatacept were 217 mcg/mL (57 to 700 mcg/mL) and 11.9 mcg/mL (0.15 to 44.6 mcg/mL) [see Clinical Studies (14.2)] . Population pharmacokinetic analyses of the serum concentration data showed that clearance of abatacept increased with baseline body weight [see Dosage and Administration (2.2)]. The estimated mean (range) clearance of abatacept in the juvenile idiopathic arthritis patients was 0.4 mL/h/kg (0.20 to 1.12 mL/h/kg). After accounting for the effect of body weight, the clearance of abatacept was not related to age and gender. Concomitant methotrexate, corticosteroids, and NSAIDs were also shown not to influence abatacept clearance.

In Study JIA-2 among patients 2 to 17 years of age, steady state of abatacept was achieved by Day 85 following the weekly body-weight–tiered subcutaneous ORENCIA dosing [see Clinical Studies (14.2)]. Comparable trough concentrations across weight tiers and age groups were achieved by the body-weight–tiered subcutaneous dosing regimen. The mean (range) trough concentration of abatacept at Day 113 was 44.4 mcg/mL (13.4 to 88.1 mcg/mL), 46.6 mcg/mL (22.4 to 97.0 mcg/mL), and 38.5 mcg/mL (9.3 to 73.2 mcg/mL) in pediatric JIA patients weighing 10 to <25 kg, 25 to <50 kg, and ≥50 kg, respectively.

Consistent with the intravenous data, population pharmacokinetic analyses for subcutaneous ORENCIA in JIA patients revealed that there was a trend toward higher clearance of abatacept with increasing body weight [see Dosage and Administration (2.2)]. Age and gender (when corrected for body weight) did not affect apparent clearance. Concomitant medication, such as methotrexate, corticosteroids, and NSAIDs, did not influence abatacept apparent clearance.

In Study PsA-I, a dose ranging study, intravenous ORENCIA was administered at 3 mg/kg, weight range-based dosing: 500 mg for patients weighing less than 60 kg, 750 mg for patients weighing 60 to 100 kg, and 1,000 mg for patients weighing greater than 100 kg, or doses of 30 mg/kg on Days 1 and 15 followed by weight-range-based dosing [see Clinical Studies (14.3)]. Following monthly intravenous ORENCIA administration, abatacept showed linear PK over the dose range in this study. At the weight-range-based dosing (see above), the steady state of abatacept was reached by Day 57 and the geometric mean (CV%) trough concentration (C_min) was 24.3 mcg/mL (40.8%) at Day 169. In Study PsA-II following weekly subcutaneous administration of ORENCIA at 125 mg, the steady state of abatacept was reached at Day 57 and the geometric mean (CV%) C_min was 25.6 mcg/mL (47.7%) at Day 169.

Consistent with the RA results, population pharmacokinetic analyses for abatacept in PsA patients revealed that there was a trend toward higher clearance (L/h) of abatacept with increasing body weight [see Dosage and Administration (2.3) ]. In addition, relative to the RA patients with the same body weight, abatacept clearance in PsA patients was approximately 8% lower, resulting in higher abatacept exposures in patients with PsA. This slight difference in exposures, however, is not considered to be clinically meaningful.

Table 8:     Pharmacokinetic Parameters (Mean, Range) in Subjects Undergoing HSCT from a Matched or 1 Allele-Mismatched Unrelated Donor in Study GVHD-1

a Cmin observed on Day 5 of the treatment period; n = 18 for the 7/8 Cohort; n = 32 for the 8/8 Cohort.Cmax, t1/2, CL, and Vss are model predicted after first 10 mg/kg ORENCIA intravenous infusion.
PK Parameter	7 of 8 Cohortn=42	8 of 8 Cohortn=73
Minimum Concentration (Cmin) a [mcg/mL]	59 (26-112)	43 (25-73)
Peak Concentration (Cmax) [mcg/mL]	221  (163-292)	172 (107-254)
Terminal half-life (t1/2) [days]	20.6 (6-43)	20.8 (12-38)
Systemic clearance (CL) [mL/h/kg]	0.26 (0.15-0.65)	0.32 (0.18-0.56)
Volume of distribution (Vss) [L/kg]	0.13 (0.08-0.27)	0.17 (0.11-0.26)

In a study of patients who received ORENCIA for prophylaxis of acute Graft Versus Host Disease (aGVHD) aged 6 years and older, the geometric mean (%CV) trough concentrations (C_min) of abatacept on Day 63 after transplant after 4 doses utilizing weight-based dosing of 10 mg/kg (maximum dose of 1,000 mg) administered on the day before transplantation (Day -1), followed by a dose on Day 5, 14, and 28 after transplant, were 22.5 mcg/mL (243.9 %CV) for recipients of 8 of 8 Human leukocyte antigen (HLA)-matched HSCTs from unrelated donors (URD), and 31.1 mcg/mL (114.4 %CV) for recipients of 7 of 8 HLA-matched HSCTs from unrelated donors (URD), respectively.

Population pharmacokinetic analyses in patients with aGVHD demonstrated that 7 of 8 HLA-matched HSCT recipients had 29% lower clearance compared to 8 of 8 HLA-matched HSCT recipients. Consistent with previous data, increasing body weight was associated with higher clearance of abatacept, while age (when corrected for body weight) did not affect apparent clearance. Concomitant medication, such as methotrexate and calcineurin inhibitors (e.g., cyclosporine and tacrolimus), did not influence abatacept clearance.

Based on population PK modeling and simulation with data from patients aged 6 and older, simulated exposures of abatacept following the first and last dose in pediatric subjects 2 to less than 6 years of age who received 15 mg/kg of ORENCIA via 60-minute intravenous infusion on Day -1, followed by 12 mg/kg via 60-minute intravenous infusion on Day 5, 14, and 28 are comparable to those in pediatric patients 6 to less than 17 years of age and adults patients who received 10 mg/kg via 60-minute intravenous infusion on Day -1, 5, 14, and 28.

13 Nonclinical Toxicology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In a mouse carcinogenicity study, weekly subcutaneous injections of 20, 65, or 200 mg/kg of abatacept administered for up to 84 weeks in males and 88 weeks in females were associated with increases in the incidence of malignant lymphomas (all doses) and mammary gland tumors (intermediate- and high-dose in females). The mice from this study were infected with murine leukemia virus and mouse mammary tumor virus. These viruses are associated with an increased incidence of lymphomas and mammary gland tumors, respectively, in immunosuppressed mice. The doses used in these studies produced exposures 0.8, 2.0, and 3.0 times higher, respectively, than the exposure associated with the maximum recommended human dose (MRHD) of 10 mg/kg based on AUC (area under the time-concentration curve). The relevance of these findings to the clinical use of ORENCIA is unknown.

In a one-year toxicity study in cynomolgus monkeys, abatacept was administered intravenously once weekly at doses up to 50 mg/kg (producing 9 times the MRHD exposure based on AUC). Abatacept was not associated with any significant drug-related toxicity. Reversible pharmacological effects consisted of minimal transient decreases in serum IgG and minimal to severe lymphoid depletion of germinal centers in the spleen and/or lymph nodes. No evidence of lymphomas or preneoplastic morphologic changes was observed, despite the presence of a virus (lymphocryptovirus) known to cause these lesions in immunosuppressed monkeys within the time frame of this study. The relevance of these findings to the clinical use of ORENCIA is unknown.

No mutagenic potential of abatacept was observed in the in vitro bacterial reverse mutation (Ames) or Chinese hamster ovary/hypoxanthine guanine phosphoribosyl-transferase (CHO/HGPRT) forward point mutation assays with or without metabolic activation, and no chromosomal aberrations were observed in human lymphocytes treated with abatacept with or without metabolic activation.

Abatacept had no adverse effects on male or female fertility in rats at doses up to 200 mg/kg every three days (11 times the MRHD exposure based on AUC).

13.2 Animal Toxicology and/or Pharmacology

In studies of adult mice and monkeys, inhibition of TDAR was apparent. However, infection and mortality, altered T-helper cells, and inflammation of thyroid and pancreas were not observed.

14 Clinical Studies

14.1 Adult Rheumatoid Arthritis

The efficacy and safety of ORENCIA for intravenous administration were assessed in six randomized, double-blind, controlled studies (five placebo-controlled and one active-controlled) in patients ≥18 years of age with active RA diagnosed according to American College of Rheumatology (ACR) criteria. Studies I, II, III, IV, and VI required patients to have at least 12 tender and 10 swollen joints at randomization, and Study V did not require any specific number of tender or swollen joints. ORENCIA or placebo treatment was given intravenously at weeks 0, 2, and 4 and then every 4 weeks thereafter in Studies I, II, III, IV, and VI.

• •Study I (NCT00279760) evaluated ORENCIA as monotherapy in 122 patients with active RA who had failed at least one non-biologic DMARD or etanercept.
• •In Study II (NCT00162266) and Study III (NCT00048568), the efficacy of ORENCIA were assessed in patients with an inadequate response to MTX and who were continued on their stable dose of MTX.
• •In Study IV (NCT00048581), the efficacy of ORENCIA was assessed in patients with an inadequate response to a TNF antagonist, with the TNF antagonist discontinued prior to randomization; other DMARDs were permitted.
• •Study V (NCT00048932) primarily assessed safety in patients with active RA requiring additional intervention in spite of current therapy with DMARDs; all DMARDs used at enrollment were continued. Patients in Study V were not excluded for comorbid medical conditions.
• •In Study VI (NCT00122382), the efficacy and safety of ORENCIA were assessed in methotrexate-naive patients with RA of less than 2 years disease duration. In Study VI, patients previously naive to methotrexate were randomized to receive ORENCIA plus methotrexate or methotrexate plus placebo.

Study I patients were randomized to receive one of three doses of ORENCIA (0.5, 2, or 10 mg/kg) or placebo ending at week 8. Study II patients were randomized to receive ORENCIA 2 or 10 mg/kg or placebo for 12 months. Study III, IV, V, and VI patients were randomized to receive a dose of ORENCIA based on weight range or placebo for 12 months (Studies III, V, and VI) or 6 months (Study IV). The dose of ORENCIA was 500 mg for patients weighing less than 60 kg, 750 mg for patients weighing 60 to 100 kg, and 1,000 mg for patients weighing greater than 100 kg.

The efficacy of ORENCIA for subcutaneous administration were assessed in Study SC-1 (NCT00559585), which was a randomized, double-blind, double-dummy, non-inferiority study that compared ORENCIA administered subcutaneously to ORENCIA administered intravenously in 1457 patients with moderate to severely active RA, receiving background methotrexate (MTX), and experiencing an inadequate response to methotrexate (MTX-IR). In Study SC-1, patients were randomized with stratification by body weight (<60 kg, 60 to 100 kg, >100 kg) to receive (1) ORENCIA 125 mg subcutaneous injections weekly, after a single intravenous loading dose of ORENCIA based on body weight or (2) ORENCIA intravenously on Days 1, 15, 29, and every four weeks thereafter. Subjects continued taking their current dose of MTX from the day of randomization.

The percent of ORENCIA-treated patients achieving ACR 20, 50, and 70 responses and major clinical response in Studies I, III, IV, and VI are shown in Table 9. ORENCIA-treated patients had higher ACR 20, 50, and 70 response rates at 6 months compared to placebo-treated patients. Month 6 ACR response rates in Study II for the 10 mg/kg group were similar to the ORENCIA group in Study III.

In Studies III and IV, improvement in the ACR 20 response rate versus placebo was observed within 15 days in some patients and within 29 days versus MTX in Study VI. In Studies II, III, and VI, ACR response rates were maintained to 12 months in ORENCIA-treated patients. ACR responses were maintained up to three years in the open-label extension of Study II. In Study III, ORENCIA-treated patients experienced greater improvement than placebo-treated patients in morning stiffness.

In Study VI, a greater proportion of patients treated with ORENCIA plus MTX achieved a low level of disease activity as measured by a DAS28-CRP less than 2.6 at 12 months compared to those treated with MTX plus placebo (Table 9). Of patients treated with ORENCIA plus MTX who achieved DAS28-CRP less than 2.6, 54% had no active joints, 17% had one active joint, 7% had two active joints, and 22% had three or more active joints, where an active joint was a joint that was rated as tender or swollen or both.

In Study SC-1, the main outcome measure was ACR 20 at 6 months. The pre-specified non-inferiority margin was a treatment difference of −7.5%. As shown in Table 10, the study demonstrated non-inferiority of ORENCIA administered subcutaneously to intravenous infusions of ORENCIA with respect to ACR 20 responses up to 6 months of treatment. ACR 50 and 70 responses are also shown in Table 9. No major differences in ACR responses were observed between intravenous and subcutaneous treatment groups in subgroups based on weight categories (less than 60 kg, 60 to 100 kg, and more than 100 kg; data not shown).

Table 9:       Clinical Responses in Controlled Trials in Patients with RA

	Percent of Patients
	Intravenous Administration								Subcutaneous or Intravenous Administration
Â	Inadequate Response to DMARDs		Inadequate Response to Methotrexate (MTX)		Inadequate Response to TNF Antagonists		MTX-Naive		Inadequate Response to MTX
Â	Study I		Study III		Study IV		Study VI		Study SC-1
*      p<0.05, ORENCIA (ORN) vs placebo (PBO) or MTX. †      p<0.01, ORENCIA vs placebo or MTX. ‡      p<0.001, ORENCIA vs placebo or MTX. §      95% CI: −4.2, 4.8 (based on prespecified margin for non-inferiority of −7.5%). a      10 mg/kg. b      Dosing based on weight range [see Dosage and Administration (2.1)]. c      Major clinical response is defined as achieving an ACR 70 response for a continuous 6-month period. d      Refer to text for additional description of remaining joint activity. e      Per protocol data is presented in table. For ITT; n=736, 721 for SC and IV ORENCIA, respectively.
Response Rate	ORNa n=32	PBOn=32	ORNb +MTXn=424	PBO+MTXn=214	ORNb +DMARDsn=256	PBO +DMARDsn=133	ORNb +MTXn=256	PBO+MTXn=253	ORNe SC+MTXn=693	ORNe IV+MTXn=678
ACR 20	Â		Â		Â		Â
Month 3	53%	31%	62%‡	37%	46%‡	18%	64%*	53%	68%	69%
Month 6	NA	NA	68%‡	40%	50%‡	20%	75%â€	62%	76%§	76%
Month 12	NA	NA	73%‡	40%	NA	NA	76%‡	62%	NA	NA
ACR 50	Â		Â		Â		Â		Â
Month 3	16%	6%	32%‡	8%	18%â€	6%	40%‡	23%	33%	39%
Month 6	NA	NA	40%‡	17%	20%‡	4%	53%‡	38%	52%	50%
Month 12	NA	NA	48%‡	18%	NA	NA	57%‡	42%	NA	NA
ACR 70	Â		Â		Â		Â		Â
Month 3	6%	0	13%‡	3%	6%*	1%	19%â€	10%	13%	16%
Month 6	NA	NA	20%‡	7%	10%â€	2%	32%â€	20%	26%	25%
Month 12	NA	NA	29%‡	6%	NA	NA	43%‡	27%	NA	NA
Major Clinical Responsec	NA	NA	14%‡	2%	NA	NA	27%‡	12%	NA	NA
DAS28-CRP <2.6d	Â		Â		Â		Â		Â
Month 12	NA	NA	NA	NA	NA	NA	41%‡	23%	NA	NA

The results of the components of the ACR response criteria for Studies III, IV, and SC-1 are shown in Table 10 (results at Baseline [BL] and 6 months [6 M]). In ORENCIA-treated patients, greater improvement was seen in all ACR response criteria components through 6 and 12 months than in placebo-treated patients.

Table 10:     Components of ACR Responses at 6 Months in Adult Patients with RA

Â	Intravenous Administration								Subcutaneous or Intravenous Administration
Â	Inadequate Response to MTX				Inadequate Response to TNF Antagonists				Inadequate Response to MTX
	Study III				Study IV				Study SC-1c
†     p<0.01, ORENCIA (ORN) vs placebo (PBO), based on mean percent change from baseline. ‡     p<0.001, ORENCIA vs placebo, based on mean percent change from baseline. a     Visual analog scale: 0 = best, 100 = worst. b     Health Assessment Questionnaire: 0 = best, 3 = worst; 20 questions; 8 categories: dressing and grooming, arising, eating,       walking, hygiene, reach, grip, and activities. c     SC-1 is a non-inferiority study. Per protocol data is presented in table.
Â	ORN+MTXn=424		PBO+MTXn=214		ORN+DMARDsn=256		PBO+DMARDsn=133		ORN SC+MTXn=693		ORN IV+MTXn=678
Component(median)	BL	6 M	BL	6 M	BL	6 M	BL	6 M	BL	6 M	BL	6 M
Number of tender joints (0-68)	28	7‡	31	14	30	13‡	31	24	27	5	27	6
Number of swollen joints(0-66)	19	5‡	20	11	21	10‡	20	14	18	4	18	3
Paina	67	27‡	70	50	73	43â€	74	64	71	25	70	28
Patient global assessmenta	66	29‡	64	48	71	44‡	73	63	70	26	68	27
Disabilityindexb	1.75	1.13‡	1.75	1.38	1.88	1.38‡	2.00	1.75	1.88	1.00	1.75	1.00
Physicianglobal assessmenta	69	21‡	68	40	71	32‡	69	54	65	16	65	15
CRP (mg/dL)	2.2	0.9‡	2.1	1.8	3.4	1.3‡	2.8	2.3	1.6	0.7	1.8	0.7

The percent of patients achieving the ACR 50 response for Study III by visit is shown in Figure 1. The time course for the ORENCIA group in Study VI was similar to that in Study III.

Figure 1:     Percent of Patients Achieving ACR 50 Response by Visit* (Study III)

*The same patients may not have responded at each time point.

The percent of patients achieving the ACR 50 response for Study SC-1 in the ORENCIA subcutaneous (SC) and intravenous (IV) treatment arms at each treatment visit was as follows: Day 15—SC 3%, IV 5%; Day 29—SC 11%, IV 14%; Day 57—SC 24%, IV 30%; Day 85—SC 33%, IV 38%; Day 113—SC 39%, IV 41%; Day 141—SC 46%, IV 47%; Day 169—SC 51%, IV 50%.

In Study III and Study VI, structural joint damage was assessed radiographically and expressed as change from baseline in the Genant-modified Total Sharp Score (TSS) and its components, the Erosion Score (ES) and Joint Space Narrowing (JSN) score. ORENCIA/MTX slowed the progression of structural damage compared to placebo/MTX after 12 months of treatment as shown in Table 11.

Table 11:     Mean Radiographic Changes in Study III^a and Study VI^b

Parameter	ORENCIA/MTX	Placebo/MTX	Differences	P-valued
a     Patients with an inadequate response to MTX. b     MTX-naive patients. c     Patients received 1 year of placebo/MTX followed by 1 year of ORENCIA/MTX. d     Based on a nonparametric ANCOVA model.
Study III	Â	Â	Â	Â
First Year
     TSS	1.07	2.43	1.36	<0.01
     ES	0.61	1.47	0.86	<0.01
     JSN score	0.46	0.97	0.51	<0.01
Second Year
     TSS	0.48	0.74c	-	-
     ES	0.23	0.22c	-	-
     JSN score	0.25	0.51c	-	-
Study VI	Â	Â	Â	Â
First Year	Â	Â	Â	Â
     TSS	0.6	1.1	0.5	0.04

In the open-label extension of Study III, 75% of patients initially randomized to ORENCIA/MTX and 65% of patients initially randomized to placebo/MTX were evaluated radiographically at Year 2. As shown in Table 11, progression of structural damage in ORENCIA/MTX-treated patients was further reduced in the second year of treatment.

Following 2 years of treatment with ORENCIA/MTX, 51% of patients had no progression of structural damage as defined by a change in the TSS of zero or less compared with baseline. Fifty-six percent (56%) of ORENCIA/MTX-treated patients had no progression during the first year compared to 45% of placebo/MTX-treated patients. In their second year of treatment with ORENCIA/MTX, more patients had no progression than in the first year (65% vs 56%).

Improvement in physical function was measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). In the HAQ-DI, ORENCIA demonstrated greater improvement from baseline versus placebo in Studies II-V and versus MTX in Study VI. In Study SC-1, improvement from baseline as measured by HAQ-DI at 6 months and over time was similar between subcutaneous and intravenous ORENCIA administration. The results from Studies II and III are shown in Table 12. Similar results were observed in Study V compared to placebo and in Study VI compared to MTX. During the open-label period of Study II, the improvement in physical function has been maintained for up to 3 years.

Table 12:     Mean Improvement from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) in Adult Patients with RA

Â	Inadequate Response to Methotrexate
Â	Study II		Study III
***  p<0.001, ORENCIA vs placebo. a      10 mg/kg. b      Dosing based on weight range [see Dosage and Administration (2.1)]. c      Modified Health Assessment Questionnaire: 0 = best, 3 = worst; 8 questions; 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. d      Health Assessment Questionnaire: 0 = best, 3 = worst; 20 questions; 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities.
HAQ Disability Index	ORENCIAa +MTX(n=115)	Placebo+MTX(n=119)	ORENCIAb +MTX(n=422)	Placebo+MTX(n=212)
Baseline (Mean)	0.98c	0.97c	1.69d	1.69d
Mean Improvement     Year 1	0.40c,***	0.15c	0.66d,***	0.37d

Health-related quality of life was assessed by the SF-36 questionnaire at 6 months in Studies II, III, and IV and at 12 months in Studies II and III. In these studies, improvement was observed in the ORENCIA group as compared with the placebo group in all 8 domains of the SF-36 as well as the Physical Component Summary (PCS) and the Mental Component Summary (MCS).

14.2 Polyarticular Juvenile Idiopathic Arthritis

The safety and efficacy of ORENCIA with intravenous administration were assessed in Study JIA-1 (NCT00095173), a three-part study including an open-label extension in pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA). Patients 6 to 17 years of age (n=190) with moderately to severely active pJIA who had an inadequate response to one or more DMARDs, such as MTX or TNF antagonists, were treated. Patients had a disease duration of approximately 4 years with moderately to severely active disease at study entry, as determined by baseline counts of active joints (mean, 16) and joints with loss of motion (mean, 16); patients had elevated C-reactive protein (CRP) levels (mean, 3.2 mg/dL) and ESR (mean, 32 mm/h). The patients enrolled had JIA subtypes that at disease onset included oligoarticular (16%), polyarticular (64%; 20% were rheumatoid factor positive), and systemic JIA without systemic manifestations (20%). At study entry, 74% of patients were receiving MTX (mean dose, 13.2 mg/m² per week) and remained on a stable dose of MTX (those not receiving MTX did not initiate MTX treatment during the study).

In Period A (open-label, lead-in), patients received 10 mg/kg (maximum 1,000 mg per dose) intravenously on days 1, 15, 29, and monthly thereafter. Response was assessed utilizing the ACR Pediatric 30 definition of improvement, defined as ≥30% improvement in at least 3 of the 6 JIA core set variables and ≥30% worsening in not more than 1 of the 6 JIA core set variables. Patients demonstrating an ACR Pedi 30 response at the end of Period A were randomized into the double-blind phase (Period B) and received either ORENCIA or placebo for 6 months or until disease flare. Disease flare was defined as a ≥30% worsening in at least 3 of the 6 JIA core set variables with ≥30% improvement in not more than 1 of the 6 JIA core set variables; ≥2 cm of worsening of the Physician or Parent Global Assessment was necessary if used as 1 of the 3 JIA core set variables used to define flare, and worsening in ≥2 joints was necessary if the number of active joints or joints with limitation of motion was used as 1 of the 3 JIA core set variables used to define flare.

At the conclusion of Period A, pediatric ACR 30/50/70 responses were 65%, 50%, and 28%, respectively. Pediatric ACR 30 responses were similar in all subtypes of JIA studied.

During the double-blind randomized withdrawal phase (Period B), ORENCIA-treated patients (intravenous) experienced significantly fewer disease flares compared to placebo-treated patients (20% vs 53%); 95% CI of the difference (15%, 52%). The risk of disease flare among patients continuing on intravenous ORENCIA was less than one-third than that for patients withdrawn from intravenous ORENCIA treatment (hazard ratio=0.31, 95% CI [0.16, 0.59]). Among patients who received intravenous ORENCIA throughout the study (Period A, Period B, and the open-label extension Period C), the proportion of pediatric ACR 30/50/70 responders has remained consistent for 1 year.

ORENCIA for subcutaneous administration without an intravenous loading dose was assessed in Study JIA-2 (NCT01844518), a 2-period, open-label study that included pediatric patients 2 to 17 years of age (n=205). Patients had active polyarticular disease at the time of the study and had inadequate response to at least one nonbiologic or biologic DMARD. The JIA patient subtypes at study entry included polyarticular (79%; 22% were rheumatoid factor positive), extended and persistent oligoarticular (14%), enthesitis-related arthritis (1%), and systemic JIA without systemic manifestations (2%). Patients had a mean disease duration of 2.5 years with active joints (mean, 11.9), joints with loss of motion (mean, 10.4), and elevated C-reactive protein (CRP) levels (mean, 1.2 mg/dL). At study entry, 80% of patients were receiving MTX and remained on a stable dose of MTX. Patients received weekly open-label ORENCIA subcutaneously by a weight-tiered dosing regimen. The primary objective of the study was evaluation of PK in order to support the extrapolation of efficacy based on exposure to ORENCIA supported by descriptive efficacy [see Clinical Pharmacology (12.3)].

JIA ACR 30/50/70 responses assessed at 4 months in the 2- to 17-year-old patients treated with subcutaneous ORENCIA were consistent with the results from intravenous ORENCIA in Study JIA-1.

14.3 Psoriatic Arthritis

The efficacy of ORENCIA was assessed in 594 adult patients (18 years and older) with psoriatic arthritis (PsA), in two randomized, double-blind, placebo-controlled studies (Studies PsA-I [NCT00534313] and PsA-II [NCT01860976]). Patients had active PsA (≥3 swollen joints and ≥3 tender joints) despite prior treatment with DMARD therapy and had one qualifying psoriatic skin lesion of at least 2 cm in diameter. In PsA-I and PsA-II, 37% and 61% of patients, respectively, were treated with TNF antagonists previously.

During the initial 24-week, double-blind period of Study PsA-I, 170 patients were randomized to receive one of four intravenous treatments on Days 1, 15, 29, and then every 28 days (there was no escape during the 24-week period):

• •Placebo
• •ORENCIA 3 mg/kg
• •ORENCIA 500 mg for patients weighing less than 60 kg, ORENCIA 750 mg for patients weighing 60 to 100 kg, and ORENCIA 1,000 mg for patients weighing greater than 100 kg (weight-range-based dosing), or
• •ORENCIA 30 mg/kg on Days 1 and 15 followed by weight range-based ORENCIA dosing (i.e., 500 mg for patients weighing less than 60 kg, 750 mg for patients weighing 60 to 100 kg, and 1,000 mg for patients weighing greater than 100 kg).

After the 24-week double blind period in Study PsA-I, patients received open-label intravenous ORENCIA every 28 days.

Patients were allowed to receive stable doses of concomitant MTX, low dose corticosteroids (equivalent to ≤10 mg of prednisone) and/or NSAIDs during the trial. At enrollment, approximately 60% of patients were receiving MTX. At baseline, the mean (SD) CRP for ORENCIA IV was 17 mg/L (33.0) and mean number (SD) of tender joints and swollen joints was 22.2 (14.3) and 10.9 (7.6), respectively.

In PsA-II, 424 patients were randomized 1:1 to receive weekly doses of subcutaneous placebo or ORENCIA 125 mg without a loading dose for 24 weeks-in a double-blind manner, followed by open-label subcutaneous ORENCIA 125 mg weekly. Patients were allowed to receive stable doses of concomitant MTX, sulfasalazine, leflunomide, hydroxychloroquine, low dose corticosteroids (equivalent to ≤10 mg of prednisone) and/or NSAIDs during the trial. At randomization, 60% of patients were receiving MTX. The baseline disease characteristics included presence of joint erosion on X-rays in 84% (341/407) with a mean (SD) PsA-modified Sharp van der Heijde erosion score (SHS) of 10.8 (24.2), elevated serum C reactive protein (CRP) in 66% [277/421]) with a mean (SD) of 14.1 mg/L (25.9), and polyarticular disease in 98% (416/424) of patients with a mean number (SD) of tender joints and swollen joints of 20.2 (13.3) and 11.6 (7.5), respectively. Patients who had not achieved at least a 20% improvement from baseline in their swollen and tender joint counts by Week 16 escaped to open-label subcutaneous ORENCIA 125 mg weekly.

The primary endpoint for both PsA-I and PsA-II was the proportion of patients achieving ACR 20 response at Week 24 (Day 169).

A greater proportion of adult patients with PsA achieved an ACR 20 response after treatment with intravenous ORENCIA (weight-range-based dosing as described above) compared to placebo in Study PsA-I and a greater proportion of adult patients with PsA achieved an ACR 20 response after treatment with subcutaneous 125 mg compared to placebo in Study PsA-II at Week 24. Responses were seen regardless of prior TNF antagonist treatment and regardless of concomitant non-biologic DMARD treatment. The percent of patients achieving ACR 20, 50, or 70 responses in Studies PsA‑I and PsA-II are presented in Table 13 below.

Table 13:     Proportion of Patients With ACR Responses at Week 24 in Studies PsA-I and PsA-II^a

Â	PsA-I		PsA-II
*      p<0.05 versus placebo. a      Patients who had less than 20% improvement in tender or swollen joint counts at Week 16 met escape criteria and were considered non-responders. b      Weight range-based intravenous dosing: ORENCIA 500 mg for patients weighing less than 60 kg, ORENCIA 750 mg for patients weighing 60 to 100 kg, and ORENCIA 1,000 mg for patients weighing greater than 100 kg.
	ORENCIA Weight-Range-Based Intravenous Dosingb N=40	Placebo N=42	ORENCIA 125 mg Subcutaneous N=213	Placebo N=211
ACR 20	47.5%*	19.0%	39.4%*	22.3%
ACR 50	25.0%	2.4%	19.2%	12.3%
ACR 70	12.5%	0%	10.3%	6.6%

The percentage of patients in PsA-II achieving ACR 20 response through Week 24 is shown below in Figure 2.

Figure 2:     Percent of Patients Achieving ACR 20 Response^a in PsA-II Study Through Week 24 (Day 169)

Results were generally consistent across the ACR components in Study PsA-I and PsA-II.

Improvements in enthesitis and dactylitis were seen with ORENCIA treatment at Week 24 in both PsA-I and PsA-II.

In study PsA-I, there was a higher proportion of patients with at least a 0.30 decrease from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 24, with an estimated difference for ORENCIA weight range-based dosing as described above (45%) vs. placebo (19%) of 26.1 (95% confidence interval: 6.8, 45.5). In study PsA-II, the proportion of patients with at least a 0.35 decrease from baseline in HAQ-DI on ORENCIA was 31%, as compared to 24% on placebo (estimated difference: 7%; 95% confidence interval: -1%, 16%). There was a higher adjusted mean change from baseline in HAQ-DI on ORENCIA (-0.33) vs. placebo (-0.20) at Week 24, with an estimated difference of -0.13 (95% confidence interval: -0.25, -0.01).

14.4 Prophylaxis of Acute Graft versus Host Disease

Study GVHD-1

The efficacy of ORENCIA, in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), for the prophylaxis of acute graft versus host disease (aGVHD), was evaluated in a multicenter, two cohort clinical study (GVHD-1, NCT01743131) in patients age 6 years and older who underwent hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor (URD). The two cohorts in GVHD-1 included:

• 1)an open-label, single-arm study of 43 patients who underwent a 7 of 8 Human Leukocyte Antigen (HLA)-matched HSCT (7 of 8 cohort); and
• 2)a randomized (1:1), double-blind, placebo-controlled study of patients who underwent an 8 of 8 HLA-matched HSCT who received ORENCIA or placebo in combination with a CNI and MTX (8 of 8 cohort).

In both the 7/8 and 8/8 cohorts, ORENCIA was administered at a dose of 10 mg/kg (1,000 mg maximum dose) as an intravenous infusion over 60 minutes, beginning on the day before transplantation (Day -1), followed by administration on Days 5, 14, and 28 after transplantation. Baseline demographic and clinical characteristics of both the 7 of 8 and 8 of 8 cohorts are outlined below in Table 14.

Table 14:     Baseline Demographic and Clinical Characteristics: 7 of 8 and 8 of 8 Cohort Treated Analysis Population in Study GVHD-1

	7 of 8 Cohort	8 of 8 Cohort
	ORENCIA (+ CNI and MTX) N=43	ORENCIA (+ CNI and MTX) N=73	Placebo (+CNI and MTX) N=69
Age - Median	38	44	40
Age - Range	6-76	6-71	7-74
Gender - Male	27 (63)	41 (56)	37 (54)
White	31 (72)	63 (86)	61 (88)
Black or African American	7 (16)	3 (4.1)	2 (2.9)
Asian	2 (4.7)	4 (6)	2 (2.9)
Hispanic	7 (16)	4 (6)	2 (2.9)
Malignancy type
   Acute Myeloid Leukemia (AML)	15 (35)	30 (41)	22 (32)
   Myelodysplastic Syndrome (MDS)	11 (26)	15 (21)	12 (17)
   Acute Lymphoblastic Leukemia (ALL)	8 (19)	20 (27)	22 (32)
   Acute leukemia or ambiguous lineage	1 (2.3)	0	1 (1.4)
   Hodgkin and Non-Hodgkin lymphoma	1 (2.3)	1 (1.4)	1 (1.4)
   Acute Lymphoblastic Lymphoma in 2nd or Greater Complete Remission	1 (2.3)	4 (6)	1 (1.4)
   Chronic Myelomonocytic leukemia	1 (2.3)	1 (1.4)	4 (6)
   Chronic Myelogenous leukemia	4 (9)	1 (1.4)	5 (7)
   Not reported	1 (2.3)	1 (1.4)	1 (1.4)
GVHD Prophylaxis
   Cyclosporine	16 (37)	11 (15)	11 (16)
   Tacrolimus	27 (63)	62 (85)	58 (84)
Type of Graft
   Bone Marrow	21 (49)	33 (45)	26 (38)
   Cytokine Mobilized Peripheral Blood (PBSC)	22 (51)	40 (55)	43 (62)
Conditioning Regimen
   TBI and Chemotherapy	11 (26)	20 (27)	26 (38)
   Busulfan and Cyclophosphamide	13 (30)	28 (38)	21 (30)
   Busulfan and Fludarabine	8 (19)	7 (10)	2 (2.9)
   Melphalan and Fludarabine	11 (26)	18 (25)	20 (29)

Efficacy was established based on overall survival (OS) and grade II-IV aGVHD free survival (GFS) results assessed at Day 180 post-transplantation. ORENCIA + CNI and MTX did not significantly improve grade III-IV GFS versus placebo + CNI and MTX at Day 180 post-transplantation. The efficacy results of the GVHD-1 8 of 8 cohort are shown in Table 15.

Table 15:     Efficacy Results in 8 of 8 Cohort in Study GVHD-1 at Day 180 Post-Transplantation

a Gr III-IV aGVHD Free Survival was measured from the date of transplantation until the onset of documented Grade III-IV aGVHD, or death by any cause up to Day 180 post-transplantation. b Gr II-IV aGVHD Free Survival was measured from the date of transplantation until the onset of documented Grade II-IV aGVHD, or death by any cause up to Day 180 post-transplantation.
Endpoint	ORENCIA (+CNI and MTX) n=73	Placebo (+CNI and MTX) n=69
Gr III-IV aGVHD Free Survivala Rate (95% CI)	87% (77%, 93%)	75% (63%, 84%)
Hazard Ratio (95% CI)	0.55 (0.26, 1.18)
Gr II-IV aGVHD Free Survivalb Rate (95% CI)	50% (38%, 61%)	32% (21%, 43%)
Hazard Ratio (95% CI)	0.54 (0.35, 0.83)
Overall Survival Rate (95% CI)	97% (89%, 99%)	84% (73%, 91%)
Hazard Ratio (95% CI)	0.33 (0.12, 0.93)

In an exploratory analysis of the 7 of 8 cohort of ORENCIA-treated patients (n=43), the rates of Grade III-IV GVHD-free survival, Grade II-IV GVHD-free survival, and overall survival at day 180 post-transplantation were 95% (95% CI 83%, 99%), 53% (95% CI 38%, 67%), and 98% (95% CI 85%, 100%), respectively.

Study GVHD-2

GVHD-2 (NCT05421299) was a clinical study that used data from the Center for International Blood and Marrow Transplant Research (CIBMTR). The study analyzed outcomes of ORENCIA in combination with a CNI and MTX, versus a CNI and MTX alone, for the prophylaxis of aGVHD, in patients 6 years of age or older who underwent HSCT from a 1 allele-mismatched URD between 2011 and 2018. The ORENCIA + CNI and MTX-treated group (n=54) included 42 patients from GVHD-1, in addition to 12 patients treated with ORENCIA outside of GVHD-1. The comparator group (n=162) was randomly selected in a 3:1 ratio to the ORENCIA-treated group from the CIBMTR registry from patients who had not received ORENCIA during the study period. Analyses used propensity score matching and inverse probability of treatment weighting to help address the impact of selection bias.

Efficacy was based on Overall Survival (OS) at Day 180 post-HSCT. The OS rate at Day 180 in the ORENCIA in combination with CNI and MTX group was 98% (95% CI: 78, 100) and the OS rate at Day 180 in the CNI and MTX group was 75% (95% CI: 67, 82).

16 How Supplied/storage And Handling

ORENCIA^® (abatacept) for injection is a white lyophilized powder for intravenous infusion after reconstitution and dilution. It is supplied as an individually packaged, single-dose vial (one may use less than the full contents of the vial or use more than one vial) with a silicone-free disposable syringe, providing 250 mg of abatacept:

                    NDC 0003-2187-10: in a clamshell presentation

                    NDC 0003-2187-13: in a carton presentation

ORENCIA^® (abatacept) injection and ORENCIA^® ClickJect (abatacept) injection are clear to slightly opalescent, colorless to pale yellow solutions for subcutaneous administration.

Prefilled Syringe

ORENCIA (abatacept) injection, 50 mg/0.4 mL, 87.5 mg/0.7 mL, and 125 mg/mL, is supplied as single-dose disposable prefilled glass syringes with BD UltraSafe Passiveâ„¢ needle guard and flange extenders.

The Type I glass syringe has a coated stopper and fixed stainless steel needle (5 bevel, 29-gauge thin wall, ½-inch needle) covered with a rigid needle shield. The prefilled syringe provides ORENCIA in the following packages:

                    NDC 0003-2814-11 (50 mg/0.4 mL): pack of 4 syringes with a passive needle safety guard

                    NDC 0003-2818-11 (87.5 mg/0.7 mL): pack of 4 syringes with a passive needle safety guard

                    NDC 0003-2188-11 (125 mg/mL): pack of 4 syringes with a passive needle safety guard

ClickJect Autoinjector

ORENCIA (abatacept) ClickJect, 125 mg/mL, is supplied as a single-dose disposable prefilled autoinjector. The Type I glass syringe contained in the autoinjector has a coated stopper and fixed stainless steel needle (5 bevel, 27-gauge special thin wall, ½-inch needle) covered with a rigid needle shield. The autoinjector provides 125 mg of abatacept in 1 mL and is provided in the following package:

                    NDC 0003-2188-51: pack of 4 autoinjectors

STORAGE AND HANDLING SECTION

Storage

Refrigerate ORENCIA lyophilized powder supplied in a vial at 2°C to 8°C (36°F to 46°F). Do not use beyond the expiration date on the vial. Protect the vials from light by storing in the original package until time of use.

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

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Inform patients that the concomitant use with other immunosuppressives (e.g., biologic DMARDs, JAK inhibitors) is not recommended [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].

Instruct patients to immediately tell their healthcare professional if they experience symptoms of an allergic reaction on the day of administration or the day after ORENCIA administration [see Warnings and Precautions (5.2)].

Inform patients that serious infections have been reported in patients receiving ORENCIA [see Warnings and Precautions (5.3)].

Inform patients that live vaccines should not be given concurrently with ORENCIA or within 3 months of its discontinuation [see Warnings and Precautions (5.4)].

Maltose is contained in ORENCIA for intravenous administration and can give falsely elevated blood glucose readings with certain blood glucose monitors on the day of ORENCIA infusion. Advise patients treated with intravenous ORENCIA who are using GDH-PQQ-based monitoring systems for glucose (e.g., diabetics) to consider using other methods for glucose monitoring. This recommendation is not applicable to patients treated with subcutaneous ORENCIA [see Drug Interactions (7.2)].

Advise patients to follow disposal instructions in the Instructions for Use. A puncture-resistant container for disposal of needles and syringes should be used. Instruct patients that they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container. Instruct patients not to recycle their used sharps disposal container.

Bristol-Myers Squibb CompanyPrinceton, New Jersey 08543 USAU.S. License Number 1713

Spl Patient Package Insert Section

adults with moderate to severe rheumatoid arthritis (RA), including those who have not been helped enough by other medicines for RA. ORENCIA may prevent further damage to your bones and joints and may help your ability to perform daily activities. In adults, ORENCIA may be used alone or with other RA treatments other than tumor necrosis factor (TNF) antagonists.

people 2 years of age and older with moderate to severe polyarticular juvenile idiopathic arthritis (pJIA). ORENCIA may be used alone or with methotrexate.

people 2 years of age and older with active psoriatic arthritis (PsA). In adults, ORENCIA can be used alone or with other PsA treatments. In children, ORENCIA can be used alone or with methotrexate.
ORENCIA is also used for the preventative treatment of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in:

people 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated-donor.
It is not known if ORENCIA is safe and effective in children less than two years of age for the treatment of pJIA.

It is not known if ORENCIA is safe and effective in children less than two years of age for the treatment of PsA.

It is not known if ORENCIA is safe and effective in children less than two years of age for the preventative treatment of aGVHD.
have any kind of infection even if it is small (such as an open cut or sore), or an infection that is in your whole body (such as the flu). If you have an infection during treatment with ORENCIA, you may have a higher chance for getting serious side effects.

have an infection that will not go away or an infection that keeps coming back.

are allergic to abatacept or any of the ingredients in ORENCIA. See the end of this Patient Information leaflet for a complete ul of ingredients in ORENCIA.

have or have had inflammation of your liver due to an infection (viral hepatitis). Your healthcare provider may examine you for hepatitis before treatment with ORENCIA.

have had a lung infection called tuberculosis (TB), a positive skin test for TB, or you recently have been in close contact with someone who has had TB. Your healthcare provider may examine you for TB or perform a skin test before treatment with ORENCIA. Symptoms of TB may include:a cough that does not go away

weight lossfever

night sweatshave a history of Epstein-Barr Virus (EBV) or Cytomegalovirus (CMV) in people receiving ORENCIA for preventative treatment of aGVHD during HSCT from an unrelated donor.

are scheduled to have surgery.

recently received a vaccination or are scheduled for a vaccination.

have a history of a breathing problem called chronic obstructive pulmonary disease (COPD).

have diabetes and use a blood glucose monitor to check your blood sugar (blood glucose) levels. ORENCIA for intravenous infusion (given through a needle placed in a vein) contains maltose, a type of sugar, that can give false high blood sugar readings with certain types of blood glucose monitors on the day of ORENCIA infusion. Your healthcare provider may tell you to use a different way to monitor your blood sugar levels.

ORENCIA for subcutaneous injection (injected under the skin) does not contain maltose. You do not need to change your blood sugar monitoring if you are using ORENCIA subcutaneously.are pregnant or plan to become pregnant. It is not known if ORENCIA can harm your unborn baby. If you took ORENCIA during pregnancy, talk to your healthcare provider before your baby receives any vaccines.are breastfeeding or plan to breastfeed. It is not known if ORENCIA passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use ORENCIA.

Some people treated with ORENCIA have developed skin cancer. Tell your healthcare provider if you have a family or personal history of skin cancer, and if you see any growths or changes in the appearance of your skin during or after your treatment with ORENCIA.Enbrel^® (etanercept)

Humira^® (adalimumab)

Remicade^® (infliximab)Kineret^® (anakinra)

Rituxan^® (rituximab)

Simponi^® (golimumab)Cimzia^® (certolizumab pegol)

Actemra^® (tocilizumab)You may receive ORENCIA given by a healthcare provider through a vein in your arm (intravenous infusion). It takes about 30 minutes to give you the full dose of medicine. You will then receive ORENCIA 2 weeks and 4 weeks after the first dose and then every 4 weeks. Intravenous administration of ORENCIA is not approved for pediatric patients with psoriatic arthritis.

You may also receive ORENCIA as an injection under your skin (subcutaneous). For home use, ORENCIA comes in a prefilled syringe or prefilled ClickJect autoinjector. Your healthcare provider will prescribe the type that is best for you. If your healthcare provider decides that you or a caregiver can give your injections of ORENCIA prefilled syringes or ORENCIA ClickJect autoinjectors at home, you or your caregiver should receive training on the right way to prepare and inject ORENCIA. Do not try to inject ORENCIA until you have been shown the right way to give the injections by your healthcare provider.

Your healthcare provider will tell you how much ORENCIA to use and when to use it.
See the Instructions for Use at the end of this Patient Information leaflet for instructions about the right way to prepare and give your ORENCIA injections at home.

For preventative treatment of aGVHD:

You will receive ORENCIA by a healthcare provider through a vein in your arm (intravenous infusion) over 60 minutes on the day before transplantation (Day -1). You will then receive ORENCIA on Days 5, 14, and 28 after transplantation.

Your healthcare provider may give you antiviral medicines before, during, and after your transplantation to help prevent Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV) infections.infections. ORENCIA can make you more likely to get infections or make the infection that you have get worse. Some people have died from these infections. Call your healthcare provider right away if you have any symptoms of an infection. Symptoms of an infection may include:fever

feel very tired

have a coughhave flu-like symptoms

warm, red, or painful skinallergic reactions. Allergic reactions can happen to people who are treated with ORENCIA. Call your healthcare provider or go to the emergency room right away if you have any symptoms of an allergic reaction. Symptoms of an allergic reaction may include:hives

swollen face, eyelids, lips, or tonguetrouble breathinghepatitis B infection in people who carry the virus in their blood. If you are a carrier of the hepatitis B virus (a virus that affects the liver), the virus can become active during treatment with ORENCIA. Your healthcare provider may do a blood test before you start treatment with ORENCIA.

vaccinations. You should not receive ORENCIA with certain types of vaccines (live vaccines). You can receive non-live vaccines, such as pneumococcal and inactivated influenza (flu) vaccines. ORENCIA may also cause some vaccinations to be less effective. Talk with your healthcare provider about your vaccination plans.

breathing problems in people with Chronic Obstructive Pulmonary Disease (COPD). You may get certain respiratory problems more often if you receive ORENCIA and have COPD. Symptoms of respiratory problems include:COPD that becomes worse

coughtrouble breathingcancer (malignancies). Certain kinds of cancer have been reported in people using ORENCIA. It is not known if ORENCIA increases your chance of getting certain kinds of cancer.

Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) infections. CMV and EBV infections and return of CMV and EBV (reactivation) have happened in people receiving ORENCIA for preventative treatment of aGVHD during unrelated HSCT. Your healthcare provider will monitor you for 6 months after transplantation and may treat you with medicines to help prevent CMV and EBV infection if needed.
The most common side effects of ORENCIA in people with RA include:
headache

upper respiratory tract infectionsore throat

nauseadiarrhea

coughfever

abdominal painlow red blood cell count

high blood pressure

CMV infection

fever

pneumonianosebleed

decreased CD4 lymphocytes

increased levels of magnesium in the blood

kidney problemsStore ORENCIA in the refrigerator at 36°F to 46°F (2°C to 8°C).

Keep ORENCIA in the original package and out of the light.

Do not freeze ORENCIA.

Safely throw away medicine that is out of date or no longer needed.
Keep ORENCIA and all medicines out of the reach of children.

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PATIENT INFORMATION ORENCIA® (oh-REN-see-ah) (abatacept) injection, for intravenous or subcutaneous use
What is ORENCIA? ORENCIA is a prescription medicine that reduces signs and symptoms in:
Before you receive or use ORENCIA, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. ORENCIA may affect the way other medicines work, and other medicines may affect the way ORENCIA works causing serious side effects. Especially tell your healthcare provider if you take other biologic medicines that may affect your immune system, such as:
You may have a higher chance of getting a serious infection if you take ORENCIA with other biologic medicines that may affect your immune system. Know the medicines you take. Keep a ul of them to show your healthcare provider and pharmacist when you get a new prescription.
How will I receive or use ORENCIA? For treatment of RA, pJIA or PsA:
What are the possible side effects of ORENCIA? ORENCIA may cause serious side effects, including:
In children and adolescents, other side effects may include:
The most common side effects of ORENCIA in prevention of aGVHD include:
These are not all the possible side effects of ORENCIA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store ORENCIA?
General information about the safe and effective use of ORENCIA. Medicines are sometimes prescribed for purposes other than those uled in a Patient Information leaflet. Do not use ORENCIA for a condition for which it was not prescribed. Do not give ORENCIA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ORENCIA that is written for health professionals.
What are the ingredients in ORENCIA? Active ingredient: abatacept Intravenous inactive ingredients: maltose, monobasic sodium phosphate, sodium chloride for administration Subcutaneous inactive ingredients: sucrose, poloxamer 188, monobasic sodium phosphate monohydrate, dibasic sodium phosphate anhydrous, water for injection.
Bristol-Myers Squibb CompanyPrinceton, NJ 08543 USA, U.S. License Number 1713 All other trademarks are property of their respective owners. For more information, go to www.ORENCIA.com or call 1-800-ORENCIA.

This Patient Information has been approved by the U.S. Food and Drug Administration.Revised: 5/2024                  

Instructions For Use

ORENCIA ^® (oh-REN-see-ah) (abatacept) Prefilled syringe with BD UltraSafe Passive ^™ needle guard
Keep the prefilled syringe in the refrigerator until ready to use.

Do not freeze.Do not remove the needle cover until you are ready to inject.

Do not pull back on the plunger at any time.

Do not recap the prefilled syringe at any time, as this may damage, bend, or break the needle.

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ORENCIA ® prefilled syringe with BD UltraSafe Passive™ needle guard (abatacept) Injection
Read these instructions before you start using your ORENCIA prefilled syringe and each time you get a refill. There may be new information. Before you use the prefilled syringe for the first time, make sure your healthcare provider shows you the right way to use it and decides that you or a caregiver may be able to give your injections of ORENCIA at home. Important:
Before you begin: get to know your prefilled syringe
There are 3 types of prefilled syringes:
The type of prefilled syringe you receive depends on the dose prescribed by your healthcare provider. The 125 mg/mL prefilled syringe is shown below.
Before use
After use
The prefilled syringe has a flange extender that makes it easier to hold and inject, and a needle guard that automatically covers the needle after a complete injection.
Go to Step 1

Step 1:  Preparing for an ORENCIA injection
Alcohol swabPrefilled syringe with UltraSafe Passive needle guardAdhesive bandageSharps disposal containerCotton ball or gauzeDo not speed up the warming process in any way, such as using the microwave or placing the syringe in warm water.

Do not remove the needle cover while allowing the prefilled syringe to reach room temperature.

 

 

 

 

 

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Gather and place supplies for your injection on a clean, flat surface. Only the prefilled syringe is included in the package:
Let your prefilled syringe warm up. Remove 1 prefilled syringe from the refrigerator and wait 30 minutes to allow it to reach room temperature.
Wash your hands well with soap and water.
Go to Step 2

Step 2: Examine the prefilled syringe
Check the expiration date printed on the label. Do not use if the expiration date has passed.

Check the prefilled syringe for damage.Do not use if it is cracked or broken.Check the liquid in the prefilled syringe through the viewing window. It should be clear and colorless to pale yellow.Do not inject if the liquid is cloudy, discolored, or has particles in it.
Note: the 50 mg prefilled syringe is shown.

Note: It is normal to see an air bubble. Do not attempt to remove it.

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Hold the prefilled syringe by the body with the needle cover pointing down as shown.
Check the Liquid.
Go to Step 3

Step 3:  Check the dose on the prefilled syringe

Hold the syringe at eye level. Look closely to make sure that the amount of liquid in the prefilled syringe is at or just above the fill line for your prescribed dose:

Do not use if your prefilled syringe does not have the correct amount of liquid. Call your pharmacist immediately.

Go to Step 4

Step 4: Choose and prepare an injection site
Each week you can use the same area of your body but use a different injection site in that area.Do not inject into an area where the skin is tender, bruised, red, scaly, or hard. Do not give the injection in any areas with scars or stretch marks.

Record the date, time, and site where you inject.Wipe the injection site with an alcohol swab and let it air dry.

Do not touch the injection site again before giving the injection.

Do not fan or blow on the clean area.Do not use the prefilled syringe if it is dropped after the needle cover is removed.

Do not use the prefilled syringe if the needle is damaged or bent.
Note: It is normal to see a drop of fluid leaving the needle.
Do not recap the prefilled syringe, as this may damage the needle.

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Choose your injection site. Choose your injection site in either the stomach (abdomen), front of the thighs, or outer area of upper arm (only if caregiver administered). Rotate injection site.

Gently clean injection site.

Remove the needle cover by holding the body of the prefilled syringe with one hand and pulling the cover straight off with your other hand. Do not put the needle cover back on the needle after you remove it. Throw away the needle cover in your household trash.

Go to Step 5

Step 5: Inject Your Dose of ORENCIA

Hold the body of the prefilled syringe in your hand using your thumb and index finger. With your other hand, pinch the area of skin you cleaned.
Insert the needle. Gently insert the needle into the pinched skin at a 45° angle.
Complete all steps to deliver your full dose of the medicine.
Inject: push the plunger with your thumb as far as it will go.	Release the needle guard: slowly lift your thumb from the plunger to activate the needle guard.		Confirm: after a complete injection, the needle guard will cover the needle and you may hear a click.
Remove the prefilled syringe and let go of the pinched skin.
Go to Step 6

Step 6: After the injection
There may be a little bleeding at the injection site. You can press a cotton ball or gauze over the injection site.

  

Do not rub the injection site.

  

If needed, you may cover the injection site with an adhesive bandage.Put your used ORENCIA prefilled syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and prefilled syringes in your household trash.

If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:made of a heavy-duty plastic,

can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,

upright and stable during use,

leak resistant, and

properly labeled to warn of hazardous waste inside the container.When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal.

Do not throw away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.Store ORENCIA in the refrigerator at 36°F to 46°F (2°C to 8°C).

Keep ORENCIA in the original package and out of the light.

Do not freeze ORENCIA.

Safely throw away medicine that is out of date or no longer needed.made of a heavy-duty plastic,

can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,

upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and injector pens. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal.

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Care of injection site:
Throwing away (disposing of) used prefilled syringes:
      Â
See Frequently Asked Questions for additional throwing away (disposal) information. If your injection is administered by a caregiver, this person must also be careful handling the syringe to prevent accidental needle stick injury and possibly spreading infection. Keep the ORENCIA prefilled syringes and the sharps disposal container out of the reach of children.
How to store ORENCIA prefilled syringe
Go to next page
Frequently Asked Questions
Q.		Why do I need to allow the prefilled syringe to warm up at room temperature for 30 minutes prior to injecting?
A.		This step is primarily for your comfort. Never try to speed up the warming process in any way, like using the microwave or placing the syringe in warm water.
Q.		Is it necessary to hold the skin pinch during the entire time I inject the dose?
A.		You must pinch the skin during needle insertion however, for your comfort you may release the skin pinch as you deliver the injection.
Q.		What if my prefilled syringe appears to be broken or damaged?
A.		Do not use the prefilled syringe. Contact your healthcare provider or pharmacist for further instructions.
Q.		What if I cannot clearly see the liquid inside the syringe?
A.		Look at the syringe closely by holding at eye level and up to the light. You may tilt the syringe slowly to get a better view of the drug fluid. If you still have trouble, contact your healthcare provider or pharmacist for further instructions.
Q.		Is it normal to feel a little bit of burning or pain during injection?
A.		You may feel a prick from the needle. Sometimes, the medicine can cause slight irritation near the injection site. Discomfort should be mild to moderate. If you have any side effects, including pain, swelling, or discoloration near the injection site, contact your healthcare provider.
Go to next page
Frequently Asked Questions
Q.		How should I dispose of a used prefilled syringe?
A.		Place the used prefilled syringe into an FDA-cleared sharps disposal container. If you do not have one you may use a household container that is:
Q.		How should I keep my prefilled syringes cool while traveling?
A.		Store them in a cool carrier between 36ºF to 46ºF (2ºC to 8ºC).Do not freeze them. Keep them in the original carton and protected from light. Your healthcare provider may know about special carrying cases.
Q.		Can I take my prefilled syringes on an airplane?
A.		Generally, you are allowed to carry your prefilled syringes with you on an airplane. Do not put them in your checked luggage. You should carry your prefilled syringes with you in your travel cooler at a temperature of 36ºF to 46ºF (2ºC to 8ºC). Keep your prefilled syringes in the original carton, and with its original preprinted labels and protected from light.
Q.		What if my prefilled syringe does not stay cool for an extended period of time? Is it dangerous to use?
A.		Contact 1-800-673-6242 for more information.
Go to back cover
If you have questions or concerns about your prefilled syringe, please contact your healthcare provider or call our toll-free help line at 1-800-673-6242.

Bristol-Myers Squibb CompanyPrinceton, NJ 08543 USA, U.S. License Number 1713

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

ORENCIA is a registered trademark of Bristol-Myers Squibb Company.BD UltraSafe Passive^â„¢ is a trademark of Becton, Dickinson, and Company.

Revised 10/2023

 

 

 

Instructions For Use

ORENCIA ^® ClickJect™ (oh-REN-see-ah) (abatacept) Prefilled autoinjector
Keep the ClickJect autoinjector in the refrigerator until ready to use.

Do not freeze.The autoinjector automatically delivers the medicine. The transparent tip locks over the needle when the injection is complete and the autoinjector is removed from the skin.

Do not remove the orange needle cover until you are ready to inject.Alcohol swabClickJect autoinjectorAdhesive bandageSharps disposal containerCotton ball or gauze

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ORENCIA ® ClickJect™ (abatacept) injection Prefilled autoinjector
125 mg/mL, single-dose autoinjector, for subcutaneous use only
Read these instructions before you use the ClickJect autoinjector and each time you get a refill. There may be new information. Before you use the autoinjector for the first time, make sure your healthcare provider shows you the right way to use it. Important:
Before you begin:
Get to know the ClickJect autoinjector
Before use
After use
Gather supplies for your injection on a clean, flat surface (only the ClickJect autoinjector is included in the package):
Go to Step 1

Step 1:  Prepare your autoinjector
Check expiration date printed on the label. Do not use if past the expiration date.

Check the autoinjector for damage.Do not use if it is cracked or broken.

Check the liquid through the viewing window. It should be clear and colorless to pale yellow. You may see a small air bubble. You do not need to remove it. Do not inject if the liquid is cloudy, discolored, or has particles in it.

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Let your ClickJect autoinjector warm up. Remove 1 autoinjector from the refrigerator and let it rest at room temperature for 30 minutes. Do not remove the autoinjector needle cover while allowing it to reach room temperature.
Wash your hands well with soap and water.
Examine the ClickJect autoinjector:
Go to Step 2
  Â

Step 2:  Prepare for injection
Each week you can use the same area of your body but use a different injection site in that area.

Do not inject into an area where the skin is tender, bruised, red, scaly, or hard. Do not give the injection in any areas with scars or stretch marks.

Record the date, time, and site where you inject.Wipe the injection site with an alcohol swab and let it air dry.

Do not touch the injection site again before giving the injection.

Do not fan or blow on the clean area.Do not twist the needle cover.

Do not recap the autoinjector.

Throw away (discard) the needle cover in yourhousehold trash.

Do not use the autoinjector if it is dropped after the needle cover is removed. Note: It is normal to see a drop of fluid leaving the needle.

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Choose your injection site in either the stomach (abdomen), front of the thighs, or outer area of upper arm (only if caregiver administered). Rotate injection site.
Gently clean injection site:
Pull orange needle cover straight off.
Go to Step 3
  Â

Step 3:  Inject your dose
You will hear a click as the injection begins.

To deliver the full dose of medicine, hold the autoinjector in place for 15 seconds and wait until the blue indicator stops moving in the window.

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Position the autoinjector so you can see the viewing window and it is at a 90° angle to the injection site. With your other hand, gently pinch the cleaned skin.
Complete all steps to deliver your full dose of medicine:
Push down on the skin to unlockthe autoinjector.	Press button, hold for 15 seconds and watch the window.
Remove the ClickJect autoinjector from the injection site by lifting it straight up. After you remove it from your skin, the transparent tip will lock over the needle. Release the pinched skin.
Go to Step 4
  Â

Step 4:  After the injection
There may be a little bleeding at the injection site. You can press a cotton ball or gauze over the injection site.

Do not rub the injection site.

If needed, you may cover the injection site with an adhesive bandage.Put your used ClickJect autoinjector in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and prefilled syringes in your household trash.

If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:made of a heavy-duty plastic,

can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,

upright and stable during use,

leak resistant, and

properly labeled to warn of hazardous waste inside the container.When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal.

Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.Store ORENCIA in the refrigerator at 36°F to 46°F (2°C to 8°C).

Keep ORENCIA in the original package and out of the light.

Do not freeze ORENCIA.

Safely throw away medicine that is out of date or no longer needed.If you do not have one, you may use a household container that is:

made of a heavy-duty plastic,

can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,

upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container.When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to throw away (dispose of) your sharps disposal container. There may be state or local laws about how you should throw away used needles and Autoinjectors. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal.

Do not recycle your used sharps disposal container.

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Care of injection site:
Throwing away (disposing of) used ClickJect autoinjectors:
      Â
See Frequently Asked Questions for additional throwing away (disposal) information. If your injection is administered by a caregiver, this person must also handle the autoinjector carefully to prevent accidental needle stick injury and possibly spreading infection.
Keep autoinjector and the sharps disposal container out of the reach of children. How to store ORENCIA ClickJect autoinjector
Continued on next page
  Â
Frequently Asked Questions
Q.		Why do I need to allow the autoinjector to warm up at room temperature for 30 minutes prior to injecting?
A.		This step is primarily for your comfort. If the medicine is cold, the injection may take longer than 15 seconds. Never try to speed the warming process in any way, like using the microwave or placing the autoinjector in warm water.
Q.		What if I accidentally remove the needle cover (orange cap) before I’m ready to use the autoinjector?
A.		If you remove the cover before you are ready to use the autoinjector, be careful. Do not try to replace it. Use the autoinjector as soon as possible. While you prepare for the injection, carefully place the autoinjector on its side on a clean, flat surface. Be sure to keep the autoinjector away from children.
Q.		What if the autoinjector appears to be broken or damaged?
A.		Do not use the autoinjector. Contact your healthcare provider or pharmacist for further instructions.
Q.		What if the injection was not triggered?
A.		Before the injection can be triggered, the device must be unlocked. To unlock, firmly push the autoinjector down on the skin without touching the button. When the stop-point is felt, the device is unlocked and can be triggered by pushing the button.
Q.		I feel a little bit of burning or pain during injection. Is this normal?
A.		When giving an injection, you may feel a prick from the needle. Sometimes, the medicine can cause slight irritation near the injection site. If this occurs, the discomfort should be mild to moderate. If you experience any side effects, including pain, swelling, or discoloration near the injection site, contact your healthcare provider or pharmacist immediately. You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Q.		How do I know I received my full dose?
A.		Before lifting the autoinjector from the injection site, check to make sure that the blue indicator has stopped moving. Then, before throwing away (disposing of) the autoinjector, check the bottom of the transparent viewing window to make sure there is no liquid left inside. If the medicine has not been completely injected, consult your healthcare provider or pharmacist.
Continued on next page
Frequently Asked Questions
Q.		How should I throw away (dispose of) a used autoinjector?
A.		Place used autoinjector into an FDA-cleared sharps disposal container right away after use.
Q.		How should I keep my autoinjector cool while traveling?
A.		Your healthcare provider or pharmacist may be familiar with special carrying cases for injectable medicines. Store in the refrigerator at 36°F to 46°F (2°C to 8°C). Do not freeze. Protect from light.
Q.		Can I take my autoinjector on board an aircraft?
A.		Generally, this is allowed. Be sure to pack your autoinjector in your carry-on, and do not put it in your checked luggage. You should carry it with you in your travel cooler at a temperature of 36°F to 46°F (2°C to 8°C) until you are ready to use it. Airport security procedures and airline policies change from time to time, so it’s best to check with airport authorities and the airline for any special rules. Prior to flying, get a letter from your healthcare provider to explain that you are traveling with prescription medicine that uses a device with a needle; if you are carrying a sharps container in your carry-on baggage, notify the screener at the airport.
Q.		What if my autoinjector does not stay cool for an extended period of time? Is it dangerous to use?
A.		Contact 1-800-673-6242 for details.
  Â
If you have questions or concerns about your autoinjector, please contact a healthcare provider or call our toll-free help line at 1-800-673-6242.

Bristol-Myers Squibb CompanyPrinceton, NJ 08543 USA, U.S. License Number 1713

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

ORENCIA is a registered trademark and ClickJect is a trademark of Bristol-Myers Squibb Company.

Revised 1/2024

      

Orencia 250 Mg/vial For Injection Representative Packaging

See How Supplied section for a complete ul of available packages of ORENCIA.

Rx onlyNDC 0003-2187-13ORENCIA^® (abatacept)Lyophilized Powder for IV Infusion250 mg/vialONLY USE THE SILICONE-FREE DISPOSABLE SYRINGE INCLUDED IN THE PACKAGE FOR RECONSTITUTIONBristol-Myers Squibb CompanyPrinceton, New Jersey 08543 USAUS License No. 1713

Orencia 50 Mg/0.4 Ml Injection Representative Packaging

Bristol-Myers SquibbNDC 0003-2814-114 Single-Dose Prefilled Syringes with BD UltraSafe Passive™ Needle GuardORENCIA®(abatacept)Injection50 mg/0.4mLSingle-Dose Prefilled Syringe with BD UltraSafe Passive™ Needle GuardFOR SUBCUTANEOUS USE ONLYWARNING: Keep out of reach of childrenDiscard each syringe after useRx only

Orencia 87.5 Mg/0.7 Ml Injection Representative Packaging

Bristol-Myers SquibbNDC 0003-2818-114 Single-Dose Prefilled Syringes with BD UltraSafe Passive™ Needle GuardORENCIA®(abatacept)Injection87.5 mg/0.7mLSingle-Dose Prefilled Syringe with BD UltraSafe Passive™ Needle GuardFOR SUBCUTANEOUS USE ONLYWARNING: Keep out of reach of childrenDiscard each syringe after useRx only

Orencia 125 Mg/ml Injection Representative Packaging

Bristol-Myers SquibbNDC 0003-2188-114 Single-Dose Prefilled Syringes with BD UltraSafe Passive^™ Needle GuardORENCIA^® (abatacept)Injection125 mg/mLSingle-Dose Prefilled Syringe with BD UltraSafe Passive^™ Needle GuardFOR SUBCUTANEOUS USE ONLYWARNING: Keep out of reach of childrenDiscard each syringe after useRx only

Orencia 125 Mg/ml Clickject Representative Packaging

Bristol-Myers SquibbNDC 0003-2188-514 Single-Dose Prefilled AutoinjectorsORENCIA^® ClickJect^™ (abatacept)Injection125 mg/mLSingle-Dose AutoinjectorFOR SUBCUTANEOUS USE ONLYRefrigerate immediatelyWARNING: Keep out of reach of childrenDiscard each autoinjector after useOpen from this side     Rx only