Get your patient on Orencia (Abatacept)

ORENCIA is a selective T cell costimulation modulator indicated for:

• •the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
  1.1 Adult Rheumatoid Arthritis

  ORENCIA^®is 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).
  1.2 Polyarticular Juvenile Idiopathic Arthritis

  ORENCIA is indicated for 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).
  1.3 Psoriatic Arthritis

  ORENCIA is indicated for 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.
  1.4 Prophylaxis for Acute Graft versus Host Disease

  ORENCIA is indicated for 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.

Concomitant use of ORENCIA with other immunosuppressives [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended. (

• •Administer at 0, 2, and 4 weeks, and every 4 weeks thereafter, as a 30-minute infusion

• •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.

• •Pediatric patients weighing <75 kg administer 10 mg/kg intravenously and those weighing ≥75 kg administer the adult intravenous dosing regimen (not to exceed a maximum dose of 1,000 mg), as a 30-minute infusion.
• •Subsequently administer infusions at 2 and 4 weeks and every 4 weeks thereafter.

• •Administer subcutaneously without an intravenous loading dose

• •Administer 125 mg by subcutaneous injection once weekly without an intravenous loading dose.
• •Patients switching from intravenous use to subcutaneous use, administer first subcutaneous dose instead of next scheduled intravenous dose.

• •For patients 6 years and older, administer at a 10 mg/kg dose (maximum dose 1,000 mg) as a 60-minute infusion on the day before transplantation, followed by a dose on Day 5, 14, and 28 after transplant.
• •For patients 2 to less than 6 years old, administer a 15 mg/kg dose as a 60-minute infusion on the day before transplantation, followed by a 12 mg/kg dose as a 60-minute infusion on Day 5, 14, and 28 after transplant.

• •Administer as a 30-minute intravenous infusion for RA, pJIA, and adult PsA.
  2.5 Preparation and Administration Instructions for Intravenous Infusion

  Calculate the ORENCIA dose, the total volume of reconstituted solution required, and the number of ORENCIA vials needed. For a full dose, less than the full contents of one vial or more than one vial may be needed. Using aseptic technique, reconstitute, dilute, and then administer ORENCIA as follows:

  Reconstitution

  • 1)Use the vial only if the vacuum is present.
  • 2)Reconstitute each vial of supplied ORENCIA lyophilized powder (each vial supplies 250 mg of abatacept) with 10 mL of Sterile Water for Injection, USP (direct the stream toward the inside wall of the vial) to obtain a concentration of 25 mg/mL. Use only the provided
    silicone-free syringe
    with an 18- to 21-gauge needle:
    • a.If the ORENCIA lyophilized powder is accidently reconstituted using a siliconized syringe, the solution may develop a few translucent particles (discard any solutions prepared using siliconized syringes).
    • b.If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe. To obtain new silicone-free syringes, contact Bristol-Myers Squibb at 1-800-ORENCIA.
  • 3)Gently swirl the vial to minimize foam formation, until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous agitation.
  • 4)Upon complete dissolution of the lyophilized powder, vent the vial with a needle to dissipate any foam that may be present.
  • 5)Visually inspect the reconstituted solution (the solution should be clear and colorless to pale yellow). Do not use if opaque particles, discoloration, or other foreign particles are present.
  • 6)Repeat steps 2) through 5) if two, three, or four vials are needed for a dose (see Table 1).

  Dilution

  • 7)Must further dilute the reconstituted ORENCIA solution to 100 mL as follows:
    • a.From a 100 mL infusion bag or bottle of 0.9% Sodium Chloride Injection, USP, withdraw a volume equal to the volume of the reconstituted ORENCIA solution required for the patient’s dose.
    • b.Slowly add the reconstituted ORENCIA solution(s) into the infusion bag or bottle using the
      silicone-free disposable syringe provided with each vial
      .
    • c.Gently mix.
      Do not shake the bag or bottle
      . The final concentration of abatacept in the bag or bottle will depend upon the amount of abatacept added, but will be no more than 10 mg/mL. Immediately discard any unused portion in the ORENCIA vial.

  Administration

  • 8)Prior to administration, visually inspect the ORENCIA diluted solution for particulate matter and discoloration. Discard the diluted solution if any particulate matter or discoloration is observed.
  • 9)Using an infusion set and a
    sterile, non-pyrogenic, low-protein-binding filter
    (pore size of 0.2 μm to 1.2 μm), administer the entire diluted ORENCIA solution over:
  • •30 minutes for RA, pJIA, and adults with PsA
  • •60 minutes for aGVHD prophylaxis
  • 10)Must complete the infusion of the diluted ORENCIA solution within 24 hours of reconstitution of the ORENCIA vials.

  Do not infuse ORENCIA concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of ORENCIA with other drugs.

  Storage of Diluted ORENCIA Solution

  May store the diluted ORENCIA solution at room temperature or refrigerate at 2ºC to 8ºC (36ºF to 46ºF) up to 24 hours before use. Discard the diluted solution if not administered within 24 hours.
• •Administer as a 60-minute intravenous infusion for aGVHD prophylaxis.
  2.5 Preparation and Administration Instructions for Intravenous Infusion

  Calculate the ORENCIA dose, the total volume of reconstituted solution required, and the number of ORENCIA vials needed. For a full dose, less than the full contents of one vial or more than one vial may be needed. Using aseptic technique, reconstitute, dilute, and then administer ORENCIA as follows:

  Reconstitution

  • 1)Use the vial only if the vacuum is present.
  • 2)Reconstitute each vial of supplied ORENCIA lyophilized powder (each vial supplies 250 mg of abatacept) with 10 mL of Sterile Water for Injection, USP (direct the stream toward the inside wall of the vial) to obtain a concentration of 25 mg/mL. Use only the provided
    silicone-free syringe
    with an 18- to 21-gauge needle:
    • a.If the ORENCIA lyophilized powder is accidently reconstituted using a siliconized syringe, the solution may develop a few translucent particles (discard any solutions prepared using siliconized syringes).
    • b.If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe. To obtain new silicone-free syringes, contact Bristol-Myers Squibb at 1-800-ORENCIA.
  • 3)Gently swirl the vial to minimize foam formation, until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous agitation.
  • 4)Upon complete dissolution of the lyophilized powder, vent the vial with a needle to dissipate any foam that may be present.
  • 5)Visually inspect the reconstituted solution (the solution should be clear and colorless to pale yellow). Do not use if opaque particles, discoloration, or other foreign particles are present.
  • 6)Repeat steps 2) through 5) if two, three, or four vials are needed for a dose (see Table 1).

  Dilution

  • 7)Must further dilute the reconstituted ORENCIA solution to 100 mL as follows:
    • a.From a 100 mL infusion bag or bottle of 0.9% Sodium Chloride Injection, USP, withdraw a volume equal to the volume of the reconstituted ORENCIA solution required for the patient’s dose.
    • b.Slowly add the reconstituted ORENCIA solution(s) into the infusion bag or bottle using the
      silicone-free disposable syringe provided with each vial
      .
    • c.Gently mix.
      Do not shake the bag or bottle
      . The final concentration of abatacept in the bag or bottle will depend upon the amount of abatacept added, but will be no more than 10 mg/mL. Immediately discard any unused portion in the ORENCIA vial.

  Administration

  • 8)Prior to administration, visually inspect the ORENCIA diluted solution for particulate matter and discoloration. Discard the diluted solution if any particulate matter or discoloration is observed.
  • 9)Using an infusion set and a
    sterile, non-pyrogenic, low-protein-binding filter
    (pore size of 0.2 μm to 1.2 μm), administer the entire diluted ORENCIA solution over:
  • •30 minutes for RA, pJIA, and adults with PsA
  • •60 minutes for aGVHD prophylaxis
  • 10)Must complete the infusion of the diluted ORENCIA solution within 24 hours of reconstitution of the ORENCIA vials.

  Do not infuse ORENCIA concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of ORENCIA with other drugs.

  Storage of Diluted ORENCIA Solution

  May store the diluted ORENCIA solution at room temperature or refrigerate at 2ºC to 8ºC (36ºF to 46ºF) up to 24 hours before use. Discard the diluted solution if not administered within 24 hours.
• •See the Full Prescribing Information for preparation and administration instructions for intravenous infusion and recommendations for subcutaneous use.
  2.5 Preparation and Administration Instructions for Intravenous Infusion

  Calculate the ORENCIA dose, the total volume of reconstituted solution required, and the number of ORENCIA vials needed. For a full dose, less than the full contents of one vial or more than one vial may be needed. Using aseptic technique, reconstitute, dilute, and then administer ORENCIA as follows:

  Reconstitution

  • 1)Use the vial only if the vacuum is present.
  • 2)Reconstitute each vial of supplied ORENCIA lyophilized powder (each vial supplies 250 mg of abatacept) with 10 mL of Sterile Water for Injection, USP (direct the stream toward the inside wall of the vial) to obtain a concentration of 25 mg/mL. Use only the provided
    silicone-free syringe
    with an 18- to 21-gauge needle:
    • a.If the ORENCIA lyophilized powder is accidently reconstituted using a siliconized syringe, the solution may develop a few translucent particles (discard any solutions prepared using siliconized syringes).
    • b.If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe. To obtain new silicone-free syringes, contact Bristol-Myers Squibb at 1-800-ORENCIA.
  • 3)Gently swirl the vial to minimize foam formation, until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous agitation.
  • 4)Upon complete dissolution of the lyophilized powder, vent the vial with a needle to dissipate any foam that may be present.
  • 5)Visually inspect the reconstituted solution (the solution should be clear and colorless to pale yellow). Do not use if opaque particles, discoloration, or other foreign particles are present.
  • 6)Repeat steps 2) through 5) if two, three, or four vials are needed for a dose (see Table 1).

  Dilution

  • 7)Must further dilute the reconstituted ORENCIA solution to 100 mL as follows:
    • a.From a 100 mL infusion bag or bottle of 0.9% Sodium Chloride Injection, USP, withdraw a volume equal to the volume of the reconstituted ORENCIA solution required for the patient’s dose.
    • b.Slowly add the reconstituted ORENCIA solution(s) into the infusion bag or bottle using the
      silicone-free disposable syringe provided with each vial
      .
    • c.Gently mix.
      Do not shake the bag or bottle
      . The final concentration of abatacept in the bag or bottle will depend upon the amount of abatacept added, but will be no more than 10 mg/mL. Immediately discard any unused portion in the ORENCIA vial.

  Administration

  • 8)Prior to administration, visually inspect the ORENCIA diluted solution for particulate matter and discoloration. Discard the diluted solution if any particulate matter or discoloration is observed.
  • 9)Using an infusion set and a
    sterile, non-pyrogenic, low-protein-binding filter
    (pore size of 0.2 μm to 1.2 μm), administer the entire diluted ORENCIA solution over:
  • •30 minutes for RA, pJIA, and adults with PsA
  • •60 minutes for aGVHD prophylaxis
  • 10)Must complete the infusion of the diluted ORENCIA solution within 24 hours of reconstitution of the ORENCIA vials.

  Do not infuse ORENCIA concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of ORENCIA with other drugs.

  Storage of Diluted ORENCIA Solution

  May store the diluted ORENCIA solution at room temperature or refrigerate at 2ºC to 8ºC (36ºF to 46ºF) up to 24 hours before use. Discard the diluted solution if not administered within 24 hours.
  2.6 Recommendations for Subcutaneous Administration

  ORENCIA prefilled syringes and ORENCIA ClickJect autoinjectors are intended for:

  • •Subcutaneous use only and are not intended for intravenous infusion.
  • •Use under the guidance of a healthcare practitioner.

  After proper training in subcutaneous injection technique, a patient or the patient’s caregiver may administer a subcutaneous injection of ORENCIA (ClickJect autoinjector or prefilled syringe) if a healthcare practitioner determines that it is appropriate. Instruct patients and/or caregivers to follow the directions provided in the Instructions for Use for additional details on administration. Specifically instruct them to inject the full amount (which provides the proper dose of ORENCIA), rotate injection sites, and to avoid injections into areas where the skin is tender, bruised, red, or hard.

  Visually inspect for particulate matter and discoloration prior to administration. Do not use ORENCIA prefilled syringes or ORENCIA ClickJect autoinjectors exhibiting particulate matter or discoloration. ORENCIA should be clear to slightly opalescent and colorless to pale yellow.
  Prepare ORENCIA using only the silicone-free disposable syringe.
  2.5 Preparation and Administration Instructions for Intravenous Infusion

  Calculate the ORENCIA dose, the total volume of reconstituted solution required, and the number of ORENCIA vials needed. For a full dose, less than the full contents of one vial or more than one vial may be needed. Using aseptic technique, reconstitute, dilute, and then administer ORENCIA as follows:

  Reconstitution

  • 1)Use the vial only if the vacuum is present.
  • 2)Reconstitute each vial of supplied ORENCIA lyophilized powder (each vial supplies 250 mg of abatacept) with 10 mL of Sterile Water for Injection, USP (direct the stream toward the inside wall of the vial) to obtain a concentration of 25 mg/mL. Use only the provided
    silicone-free syringe
    with an 18- to 21-gauge needle:
    • a.If the ORENCIA lyophilized powder is accidently reconstituted using a siliconized syringe, the solution may develop a few translucent particles (discard any solutions prepared using siliconized syringes).
    • b.If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe. To obtain new silicone-free syringes, contact Bristol-Myers Squibb at 1-800-ORENCIA.
  • 3)Gently swirl the vial to minimize foam formation, until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous agitation.
  • 4)Upon complete dissolution of the lyophilized powder, vent the vial with a needle to dissipate any foam that may be present.
  • 5)Visually inspect the reconstituted solution (the solution should be clear and colorless to pale yellow). Do not use if opaque particles, discoloration, or other foreign particles are present.
  • 6)Repeat steps 2) through 5) if two, three, or four vials are needed for a dose (see Table 1).

  Dilution

  • 7)Must further dilute the reconstituted ORENCIA solution to 100 mL as follows:
    • a.From a 100 mL infusion bag or bottle of 0.9% Sodium Chloride Injection, USP, withdraw a volume equal to the volume of the reconstituted ORENCIA solution required for the patient’s dose.
    • b.Slowly add the reconstituted ORENCIA solution(s) into the infusion bag or bottle using the
      silicone-free disposable syringe provided with each vial
      .
    • c.Gently mix.
      Do not shake the bag or bottle
      . The final concentration of abatacept in the bag or bottle will depend upon the amount of abatacept added, but will be no more than 10 mg/mL. Immediately discard any unused portion in the ORENCIA vial.

  Administration

  • 8)Prior to administration, visually inspect the ORENCIA diluted solution for particulate matter and discoloration. Discard the diluted solution if any particulate matter or discoloration is observed.
  • 9)Using an infusion set and a
    sterile, non-pyrogenic, low-protein-binding filter
    (pore size of 0.2 μm to 1.2 μm), administer the entire diluted ORENCIA solution over:
  • •30 minutes for RA, pJIA, and adults with PsA
  • •60 minutes for aGVHD prophylaxis
  • 10)Must complete the infusion of the diluted ORENCIA solution within 24 hours of reconstitution of the ORENCIA vials.

  Do not infuse ORENCIA concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of ORENCIA with other drugs.

  Storage of Diluted ORENCIA Solution

  May store the diluted ORENCIA solution at room temperature or refrigerate at 2ºC to 8ºC (36ºF to 46ºF) up to 24 hours before use. Discard the diluted solution if not administered within 24 hours.

• •
  Intravenous Infusion
•  For injection: 250 mg white lyophilized powder in a single-dose vial
  [see

  2.1 Dosage in Adult Rheumatoid Arthritis

  For adult patients with RA, administer as an intravenous infusion or as a subcutaneous injection. ORENCIA may be used as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than JAK inhibitors or bDMARDs (e.g., TNF antagonists).

  Intravenous Dosage

  Reconstitute ORENCIA lyophilized powder and administer after dilution

  [seeDosage and Administration (2.5)]

  as a 30-minute intravenous infusion utilizing the weight range-based dosing recommended in Table 1. Following the initial intravenous infusion, administer as an intravenous infusion at 2 and 4 weeks and every 4 weeks thereafter.

  Table 1:     Dose of ORENCIA for Intravenous Infusion in Adult RA Patients

  Body Weight of Adult Patient	Dose	Number of Vialsa
  aEach vial provides 250 mg of abatacept for administration.
  Less than 60 kg	500 mg	2
  60 to 100 kg	750 mg	3
  More than 100 kg	1,000 mg	4

  Subcutaneous Dosage

  Prior to the first subcutaneous dose, an optional loading dose may be administered as a single intravenous infusion (as per body weight categories in Table 1). If an intravenous loading dose is used, administer the first subcutaneous injection within one day of the infusion. Administer ORENCIA 125 mg in prefilled syringes or in ORENCIA ClickJect™ autoinjector by subcutaneous injection once weekly

  [seeDosage and Administration (2.6)]

  .

  For patients switching from ORENCIA intravenous therapy to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled intravenous dose.

  ,

  2.2 Dosage in Polyarticular Juvenile Idiopathic Arthritis

  For pediatric patients with pJIA, either administer ORENCIA as an intravenous infusion (only patients 6 years of age and older) or as a subcutaneous injection (only patients 2 years of age and older)

  [seeUse in Specific Populations (8.4)]

  . ORENCIA may be used as monotherapy or concomitantly with methotrexate.

  Intravenous Dosage

  Administer ORENCIA as a 30-minute intravenous infusion based on body weight

  [seeDosage and Administration (2.5)]

  :

  • •For body weight less than 75 kg, administer a dose of 10 mg/kg.
  • •For body weight of 75 kg or greater, administer as per the recommendations in Table 1 (follow the adult intravenous dosing regimen), not to exceed a maximum dose of 1,000 mg.

  Following the initial intravenous infusion, administer infusions at 2 and 4 weeks and every 4 weeks thereafter. Immediately discard any unused portion in the vials.

  Subcutaneous Dosage

  Administer ORENCIA for subcutaneous injection, without an intravenous loading dose, utilizing the weight range-based dosing as recommended in Table 2

  [seeDosage and Administration (2.6)]

  . Subsequently administer once weekly.

  Table 2:      Dose of ORENCIA for Subcutaneous Administration in Patients 2 Years of Age and Older with pJIA

  Body Weight of Pediatric Patient	Dose (once weekly)
  10 to less than 25 kg	50 mg
  25 to less than 50 kg	87.5 mg
  50 kg or more	125 mg

  Patients with pJIA may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determine it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested.

  ,

  2.3 Dosage in Psoriatic Arthritis

  Adult Patients

  For adult patients with psoriatic arthritis, administer as an intravenous infusion or a subcutaneous injection.

  ORENCIA may be used with or without non-biologic DMARDs.

  Intravenous Dosage

  Administer ORENCIA as a 30-minute intravenous infusion utilizing the weight range-based dosing specified in Table 1. Following the initial intravenous administration, administer an intravenous infusion at 2 and 4 weeks and every 4 weeks thereafter.

  Subcutaneous Dosage

  Administer 125 mg of ORENCIA subcutaneously once weekly (no intravenous loading dose is needed)

  [seeDosage and Administration (2.6)]

  .

  For patients switching from ORENCIA intravenous infusions to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled intravenous dose.

  Pediatric Patients

  Administer ORENCIA as a subcutaneous injection in pediatric patients 2 years of age and older with psoriatic arthritis

  [seeUse in Specific Populations (8.4)]

  . ORENCIA may be used as monotherapy or concomitantly with methotrexate. Intravenous administration is not approved for pediatric patients with psoriatic arthritis.

  Subcutaneous Dosage

  Administer ORENCIA for subcutaneous injection weekly, utilizing the weight range-based dosage as recommended in Table 3

  [seeDosage and Administration (2.6)]

  .

  Table 3: Dose of ORENCIA for Subcutaneous Administration in Patients 2 Years of Age and Older with Psoriatic Arthritis

  Body Weight of Pediatric Patient	Dose (once weekly)
  10 to less than 25 kg	50 mg
  25 to less than 50 kg	87.5 mg
  50 kg or more	125 mg

  Pediatric patients with psoriatic arthritis may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determine it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested.

  ,

  2.5 Preparation and Administration Instructions for Intravenous Infusion

  Calculate the ORENCIA dose, the total volume of reconstituted solution required, and the number of ORENCIA vials needed. For a full dose, less than the full contents of one vial or more than one vial may be needed. Using aseptic technique, reconstitute, dilute, and then administer ORENCIA as follows:

  Reconstitution

  • 1)Use the vial only if the vacuum is present.
  • 2)Reconstitute each vial of supplied ORENCIA lyophilized powder (each vial supplies 250 mg of abatacept) with 10 mL of Sterile Water for Injection, USP (direct the stream toward the inside wall of the vial) to obtain a concentration of 25 mg/mL. Use only the provided
    silicone-free syringe
    with an 18- to 21-gauge needle:
    • a.If the ORENCIA lyophilized powder is accidently reconstituted using a siliconized syringe, the solution may develop a few translucent particles (discard any solutions prepared using siliconized syringes).
    • b.If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe. To obtain new silicone-free syringes, contact Bristol-Myers Squibb at 1-800-ORENCIA.
  • 3)Gently swirl the vial to minimize foam formation, until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous agitation.
  • 4)Upon complete dissolution of the lyophilized powder, vent the vial with a needle to dissipate any foam that may be present.
  • 5)Visually inspect the reconstituted solution (the solution should be clear and colorless to pale yellow). Do not use if opaque particles, discoloration, or other foreign particles are present.
  • 6)Repeat steps 2) through 5) if two, three, or four vials are needed for a dose (see Table 1).

  Dilution

  • 7)Must further dilute the reconstituted ORENCIA solution to 100 mL as follows:
    • a.From a 100 mL infusion bag or bottle of 0.9% Sodium Chloride Injection, USP, withdraw a volume equal to the volume of the reconstituted ORENCIA solution required for the patient’s dose.
    • b.Slowly add the reconstituted ORENCIA solution(s) into the infusion bag or bottle using the
      silicone-free disposable syringe provided with each vial
      .
    • c.Gently mix.
      Do not shake the bag or bottle
      . The final concentration of abatacept in the bag or bottle will depend upon the amount of abatacept added, but will be no more than 10 mg/mL. Immediately discard any unused portion in the ORENCIA vial.

  Administration

  • 8)Prior to administration, visually inspect the ORENCIA diluted solution for particulate matter and discoloration. Discard the diluted solution if any particulate matter or discoloration is observed.
  • 9)Using an infusion set and a
    sterile, non-pyrogenic, low-protein-binding filter
    (pore size of 0.2 μm to 1.2 μm), administer the entire diluted ORENCIA solution over:
  • •30 minutes for RA, pJIA, and adults with PsA
  • •60 minutes for aGVHD prophylaxis
  • 10)Must complete the infusion of the diluted ORENCIA solution within 24 hours of reconstitution of the ORENCIA vials.

  Do not infuse ORENCIA concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of ORENCIA with other drugs.

  Storage of Diluted ORENCIA Solution

  May store the diluted ORENCIA solution at room temperature or refrigerate at 2ºC to 8ºC (36ºF to 46ºF) up to 24 hours before use. Discard the diluted solution if not administered within 24 hours.

  )]
  .
• •
  Subcutaneous Use
•  Injection: 50 mg/0.4 mL, 87.5 mg/0.7 mL, and 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled glass syringe.
•  Injection: 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled ClickJect autoinjector.

The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. However, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while

None.

• •Concomitant use with a TNF antagonist can increase the risk of infections and serious infections.
  5.1 Increased Risk of Infection with Concomitant Use of TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors

  In controlled clinical trials in patients with adult RA, patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs. 43%) and serious infections (4.4% vs. 0.8%) compared to patients treated with only TNF antagonists

  [seeAdverse Reactions (6.1)]

  . These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of ORENCIA with TNF antagonists; therefore, concurrent therapy with ORENCIA and a TNF antagonist is not recommended. While transitioning from TNF antagonist therapy to ORENCIA therapy, patients should be monitored for signs of infection. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.
• •Hypersensitivity and anaphylaxis have occurred.
  5.2 Hypersensitivity Reactions

  In clinical trials of 2688 adult RA patients treated with intravenous ORENCIA, there were two cases (<0.1%) of anaphylaxis reactions. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in less than 0.9% of ORENCIA-treated patients. Of the 190 ORENCIA-treated patients in pJIA clinical trials, there was one case of a hypersensitivity reaction (0.5%)

  [seeAdverse Reactions (6.1)]

  .

  In postmarketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days).

  Appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately with appropriate therapy instituted, and the use of ORENCIA should be permanently discontinued.
• •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.
  5.3 Infections

  Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA (serious infections were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively)

  [seeAdverse Reactions (6.1)]

  . Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which in addition to their underlying disease, could further predispose them to infection. A higher rate of serious infections has been observed in adult RA patients treated with concurrent TNF antagonists and ORENCIA compared to those treated with ORENCIA alone

  [seeWarnings and Precautions (5.1)]

  .

  Healthcare providers should exercise caution when considering the use of ORENCIA in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.

  Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA.

  Antirheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with ORENCIA. In clinical studies with ORENCIA, patients who screened positive for hepatitis were excluded from study.
• •Screen for latent TB infection prior to initiating therapy. Patients testing positive should be treated prior to initiating ORENCIA.
  5.3 Infections

  Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA (serious infections were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively)

  [seeAdverse Reactions (6.1)]

  . Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which in addition to their underlying disease, could further predispose them to infection. A higher rate of serious infections has been observed in adult RA patients treated with concurrent TNF antagonists and ORENCIA compared to those treated with ORENCIA alone

  [seeWarnings and Precautions (5.1)]

  .

  Healthcare providers should exercise caution when considering the use of ORENCIA in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.

  Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA.

  Antirheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with ORENCIA. In clinical studies with ORENCIA, patients who screened positive for hepatitis were excluded from study.
• •Screen for viral hepatitis prior to initiating ORENCIA.
  5.3 Infections

  Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA (serious infections were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively)

  [seeAdverse Reactions (6.1)]

  . Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which in addition to their underlying disease, could further predispose them to infection. A higher rate of serious infections has been observed in adult RA patients treated with concurrent TNF antagonists and ORENCIA compared to those treated with ORENCIA alone

  [seeWarnings and Precautions (5.1)]

  .

  Healthcare providers should exercise caution when considering the use of ORENCIA in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.

  Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA.

  Antirheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with ORENCIA. In clinical studies with ORENCIA, patients who screened positive for hepatitis were excluded from study.
• •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.
  5.4 Immunizations

  Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. ORENCIA-treated patients may receive current non-live vaccines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving ORENCIA. In addition, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while

  in utero [seeUse in Specific Populations (8.1)]

  . Based on its mechanism of action, ORENCIA may blunt the effectiveness of some immunizations.
• •COPD patients may develop more frequent respiratory adverse reactions.
  5.5 Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD)

  In Study V, adult COPD patients treated with ORENCIA for RA developed adverse reactions more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to patients treated with placebo (27% vs 6%)

  [seeClinical Studies (14.1)andAdverse Reactions (6.1)]

  . Use of ORENCIA in patients with COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.
• •Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) reactivation in patients treated for aGVHD prophylaxis.
  5.7 Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT)

  Post-Transplant Lymphoproliferative Disorder (PTLD) occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 4 patients (3.4%) experienced PTLD. All the PTLD events were associated with Epstein-Barr virus (EBV) infection. Three of the four patients were EBV serology positive at baseline; one patient had negative baseline EBV serology with donor EBV serology unknown. Three of the 4 patients discontinued acyclovir prophylaxis at day 30 post-transplant. The range of time to onset of the events was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Provide prophylaxis for EBV infection for 6 months post-transplantation to prevent EBV-associated PTLD

  [seeDosage and Administration (2.4)]

  .

  Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7% experienced CMV invasive diseases up to day 225 post-transplant. All the patients who experienced CMV invasive disease were CMV serology positive at baseline. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract

  [seeAdverse Reactions (6.1)]

  .

  Monitor patients for CMV infection/reactivation for 6 months post-transplant regardless of the results of donor and recipient pre-transplant CMV serology. Consider prophylaxis for CMV infection/reactivation

  [seeDosage and Administration (2.4)]

  .

Antibodies directed against the entire abatacept molecule or to the CTLA-4 portion of abatacept were assessed by ELISA assays in RA patients for up to 2 years following repeated treatment with intravenous ORENCIA. Thirty-four of 1993 (2%) patients developed binding antibodies to the entire abatacept molecule or to the CTLA-4 portion of abatacept. Because trough levels of abatacept can interfere with assay results, a subset analysis was performed. In the subset analysis, 9 of 154 (6%) patients that had discontinued intravenous ORENCIA treatment for over 56 days developed antibodies. Samples with confirmed binding activity to CTLA-4 were assessed for the presence of neutralizing antibodies in a cell-based luciferase reporter assay. Six of 9 (67%) evaluable patients were shown to possess neutralizing antibodies. However, the development of neutralizing antibodies may be underreported due to lack of assay sensitivity.

No correlation of anti-abatacept antibody development to clinical response or adverse events was observed.

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.

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).

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

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 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

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).

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.

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 0003-2187-13: in a carton presentation

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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

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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

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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

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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 unlock the 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

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Care of injection site:
Throwing away (disposing of) used ClickJect autoinjectors:
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
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.
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 Company

Princeton, 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

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.