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In moderate to severe rheumatoid arthritis (RA)
ORENCIA offers flexible administration options1
For patients who require administration under the supervision of a healthcare professional—or prefer not to self-inject—ORENCIA offers an intravenous (IV) infusion option.
ORENCIA IV is available as a 30-minute infusion
4-week dosing schedule
Following the starter doses, ORENCIA IV is maintained with a regular
*Actual day of dosing may vary based on patient scheduling.
Adult weight-based dosing
- Reconstitute ORENCIA lyophilized powder and administer after dilution.
- For injection: 250 mg white lyophilized powder in a single-dose vial (one may use less than the full contents of the vials or use more than one vial).
- Immediately discard any unused portion in the vials.
If there are any product defects, call
The appropriate dose may require 2, 3, or 4 vials based on patient weight.
National Drug Code (NDC):
0003-2187-10 (in a clamshell presentation)
0003-2187-13 (in a carton presentation)
ORENCIA IV infusion
for preparing and administering an
ORENCIA IV infusion.
If you need Adobe Reader, click the link below to download
the free reader. Link to Adobe Reader Download page.
Storage and handling for ORENCIA IV
- Refrigerate ORENCIA lyophilized powder at 36°F to 46°F (2°C to 8°C)
- 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
Patients switching from ORENCIA IV to ORENCIA SC administration should take their first SC dose instead of their next scheduled IV dose.
ORENCIA IV infusion
for preparing and administering an
ORENCIA IV infusion.
If you need Adobe Reader, click the link below to download
the free reader. Link to Adobe Reader Download page.
Watch the step-by-step video guide for
ORENCIA IV infusion
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Indication and Usage
Adult Rheumatoid Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.
Please see full Important Safety Information at the conclusion of this presentation.
Hello, and welcome to “Infusing ORENCIA (abatacept) IV,” a video guide to preparing and administering an infusion of ORENCIA, a treatment indicated for moderately to severely active Rheumatoid Arthritis.
Indication and Usage
Adult Rheumatoid Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants, [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.
This video is divided up into 5 modules and designed to give you all the essential information you'll need to effectively and efficiently administer ORENCIA IV.
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Important steps in preparing and administering ORENCIA
- Determining weight-based dosing
- Reconstitution
- Infusion
- FAQs
We'll review 4 key steps in the process for preparing and administering an ORENCIA infusion:
- Determining weight-based dosing
- Reconstituting ORENCIA IV
- Infusing ORENCIA IV
- And finally, some frequently asked questions you may get.
Now, let's go over some helpful information to keep in mind when preparing and administering ORENCIA IV.
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MODULE 1
GENERAL ADMINISTRATION INFORMATION.
Module one. General administration information.
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PROTECT FROM LIGHT
ORENCIA vials need to be protected from light. Make sure to store the vials in their original packaging until you're ready to use them.
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REFRIGERATE 36°F to 46°F
ORENCIA IV lyophilized powder must be refrigerated at 36 to 46 degrees Fahrenheit.
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CHECK EXPIRATION MONTH AND YEAR
Always check the expiration date on the ORENCIA vial. Do not use the vial beyond the expiration date. Be sure to closely inspect the packaging and vials before use. If there are any defects, call 1-800-ORENCIA to receive a new vial.
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USE ONLY THE SILICONE-FREE DISPOSABLE SYRINGE
Remember to only use the silicone-free disposable syringes provided with each vial. If the syringe breaks or becomes contaminated, throw it away and use a new silicone-free disposable syringe. If the ORENCIA powder is accidentally reconstituted using a siliconized syringe, the solution may develop a few translucent particles. Be sure to discard any solutions right away that have been prepared using a siliconized syringe.
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USE WITHIN 24 HRS
ORENCIA IV must be administered within 24 hours of reconstitution.
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USE IMMEDIATELY OR STORE DILUTED SOLUTION
ROOM 36°F to 46°F
Once the ORENCIA IV solution is fully diluted, either use it immediately, or store the solution at room temperature, or refrigerate at 36 to 46 degrees Fahrenheit.
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INFUSION TIME 30 MIN
And finally, an ORENCIA infusion lasts 30 minutes.
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Important Safety Information for ORENCIA® (abatacept)
Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, 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, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.
Please see full Important Safety Information at the conclusion of this presentation.
Important Safety Information for ORENCIA® (abatacept)
Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, 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, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.
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MODULE 2
WEIGHT-BASED DOSING AND YOUR PATIENTS.
Module two. Weight-based dosing and your patients.
The appropriate ORENCIA IV dose for infusion is determined by utilizing weight-based dosing.
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- Lyophilized powder in single-use vials
- Each vial contains 250 mg of ORENCIA® (abatacept)
ORENCIA IV is supplied as lyophilized powder in single-use vials, and each vial contains 250 milligrams of ORENCIA. To determine the appropriate weight-based dose for infusion, here are the formulas to use:
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<132 lb
500 MILLIGRAMS
For patients who weigh less than 132 pounds, you'll need 500 milligrams, which equals 2 vials.
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132 to 220 lb
750 MILLIGRAMS
For patients who weigh 132 to 220 pounds, you'll need 750 milligrams, which equals 3 vials.
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>220 lb
1000 MILLIGRAMS
And for patients who weigh more than 220 pounds, you'll need 1000 milligrams, which equals 4 vials.
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Important Safety Information for ORENCIA® (abatacept)
Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, suchas hypotension, urticaria, and dyspnea, each occurred in <0.9%of patients. ln 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 treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.
Please see full Important Safety Information at the conclusion of this presentation.
Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. 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 treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.
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MODULE 3
HOW TO RECONSTITUTE ORENCIA® (abatacept) IV
Module three. How to reconstitute ORENCIA IV.
Let's go through the reconstitution and dilution process for ORENCIA IV.
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SUPPLIES
Here are the supplies you'll need to reconstitute ORENCIA:
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<132 lb = 2 vials
132 - 220 lb = 3 vials
>220 lb = 4 vials
The appropriate number of ORENCIA vials – 2, 3, or 4 – based on your patient's weight-based dose.
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USE ONLY THE SILICONE-FREE DISPOSABLE SYRINGE
APPROPRIATE NUMBER OF ORENCIA VIALS (2, 3, OR 4)
A silicone-free disposable syringe that's provided with each ORENCIA vial. Remember, always use a silicone-free syringe for reconstituting ORENCIA.
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SILICONE-FREE DISPOSABLE SYRINGE
APPROPRIATE NUMBER OF ORENCIA VIALS (2, 3, OR 4)
STERILE WATER, USP
100-ML INFUSION BAG OR BOTTLE OF 0.9% SODIUM CHLORIDE INJECTION, USP
18- TO 21-GAUGE NEEDLES.
ALCOHOL SWABS
Sterile Water for Injection, USP.
A 100-milliliter infusion bag or bottle of 0.9% Sodium Chloride Injection, USP.
18- to 21-gauge needles.
And alcohol swabs.
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RECONSTITUTION
Now let's go over the reconstitution process:
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Important Safety Information for ORENCIA® (abatacept)
Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. 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. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.
Please see full Important Safety Information at the conclusion of this presentation.
But before we do.
Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. 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. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.
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Use 10 mL Sterile Water for Injection, USP, per vial
You'll need to reconstitute each vial of ORENCIA IV powder with 10 milliliters of Sterile Water for Injection, USP.
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USE ONLY THE SILICONE-FREE DISPOSABLE SYRINGE
Using only the silicone-free disposable syringe and an 18- to 21-gauge needle, withdraw 10 milliliters of Sterile Water for Injection, USP.
Remove the flip top from the vial of ORENCIA IV and wipe the top with an alcohol swab.
Insert the syringe of Sterile Water for Injection, USP, into the ORENCIA vial through the center of the rubber stopper. Direct the stream of liquid to the side of the vial, injecting all 10 milliliters.
Rotate the vial gently in a swirling motion until the contents are completely dissolved.
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DO NOT SHAKE
It's important not to shake the vial and avoid agitation. When the powder is completely dissolved, vent the vial with a needle to dissipate any foam that may have formed. The solution should be clear and colorless to pale yellow. Don't use the solution if there are opaque particles, discoloration, or other foreign particles visible.
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DILUTION
Now you're ready to dilute the ORENCIA IV solution in the infusion bag:
From a 100-milliliter infusion bag or bottle, withdraw a volume of 0.9% Sodium Chloride Injection, USP, equal to the volume of reconstituted ORENCIA IV solution required for the patient's dose:
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2 vials, remove 20 mL
3 vials, remove 30 mL
4 vials, remove 40 mL
For 2 vials, remove 20 milliliters. For 3 vials, remove 30 milliliters. And for 4 vials, remove 40 milliliters.
Now, using the same silicone-free disposable syringe, slowly add the reconstituted ORENCIA IV solution into the infusion bag or bottle.
Gently mix the contents, making sure not to shake the bag or bottle, to complete the reconstitution.
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USE WITHIN 24 HRS
The fully diluted ORENCIA solution must be administered within 24 hours of reconstitution.
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USE IMMEDIATELY OR STORE DILUTED SOLUTION
ROOM 36°F to 46°F
Once the ORENCIA IV solution is fully diluted, either use it immediately, or store the solution at room temperature, or refrigerate at 36 to 46 degrees Fahrenheit.
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Important Safety Information for ORENCIA® (abatacept)
Immunizations: Prior to initiating ORENCIA in adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.
Please see full Important Safety Information at the conclusion of this presentation.
Immunizations: Prior to initiating ORENCIA in adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.
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Important Safety Information for ORENCIA® (abatacept)
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 events more frequently than those treated with placebo (97% vs 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.
Please see full Important Safety Information at the conclusion of this presentation.
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 events more frequently than those treated with placebo (97% vs 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.
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MODULE 4
ORENCIA® (abatacept) INFUSION PROTOCOL
Module four. ORENCIA infusion protocol.
Here are some important things to remember when you're administering an ORENCIA infusion. For first-time infusion patients, be sure to check the patient's full medical history and perform the appropriate tests prior to giving the infusion.
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- Check vital signs
- Ask about:
- Fever
- Cold
- Infection
- Other health issues
For all patients, check their vital signs before infusion. Ask your patients if there have been any changes in the past month that would keep them from receiving an ORENCIA infusion such as a fever, cold, infection, or any other health issues.
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Important Safety Information for ORENCIA® (abatacept)
Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.
Please see full Important Safety Information at the conclusion of this presentation.
Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.
Prior to administration, visually inspect the ORENCIA solution for particulate matter and discoloration. Discard the solution if any particulate matter or discoloration is present.
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ORENCIA must be administered with an infusion set and a sterile, nonpyrogenic, low-protein-binding filter (pore size of 0.2 µm to 1.2 µm)
ORENCIA must be administered with an infusion set and a sterile, nonpyrogenic, low protein-binding filter with a pore size of 0.2 to 1.2 microns.
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Do not infuse ORENCIA IV in the same IV line with other agents
And most importantly, do not infuse ORENCIA IV in the same IV line with other agents.
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INFUSION TIME 30 MIN
The ORENCIA infusion will last 30 minutes.
Be sure to check the patient's vital signs once again before the end of the infusion.
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FEVER
FEELS VERY TIRED
COUGH
FLU-LIKE SYMPTOMS
WARM, RED, OR PAINFUL SKIN
Before the patients leave, remind them to call the doctor immediately if they feel sick or experience any of the following signs of infection such as:
- Fever
- Feeling very tired
- Coughing
- Flu-like symptoms
- Or warm, red, or painful skin
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DIZZINESS
HEADACHE
HYPERTENSION
Remember, the most frequently reported acute infusion-related events occurring within one hour of infusion were dizziness, headache, and hypertension.
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Patients with diabetes may get a false high blood sugar reading on test strips with glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ)
Also, tell patients with diabetes that on the day of treatment with ORENCIA IV, they may get a false high blood sugar reading on test strips with GDHPQQ. ORENCIA IV contains maltose, a type of sugar. Therefore, you may want to recommend to these patients that they use a different testing monitor to avoid a possible false reading.
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MODULE 5
FREQUENTLY ASKED QUESTIONS
Module five. Frequently asked questions.
Generally speaking, be prepared to explain the infusion procedure, and tell patients specifically about what they can expect during an ORENCIA infusion.
For all patients, be sure to ask how they're doing since the last infusion. You may want to ask if they've felt any difference in joint stiffness or pain.
Here are some frequently asked questions and some additional information about the ORENCIA infusion process.
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How long will an ORENCIA® (abatacept) infusion take?
How long will an ORENCIA infusion take?
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INFUSION TIME 30 MIN
ORENCIA IV is a 30-minute infusion. Altogether, patients will probably be at the infusion center for about an hour.
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What will the infusion feel like?
What will the infusion feel like?
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Expect a small pinch from the needle
Alert staff of anything unusual once infusion begins
Patients will be seated with their arm resting comfortably. They will feel a small pinch when the needle is inserted into the arm at the beginning of the infusion process. If anything feels uncomfortable or unusual after that, or at any time during the infusion, they should notify a nurse immediately.
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What are some of the possible signs and symptoms of infusion reactions?
What are some of the possible signs and symptoms of infusion reactions?
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Patients should get emergency help immediately for:
- Hives
- Swollen face, eyelids, lips, or tongue
- Trouble breathing
Allergic reactions can happen to people who use ORENCIA. Patients need to contact their healthcare provider immediately or get emergency medical help right away if they have hives, a swollen face, eyelids, lips, or tongue, or if they have trouble breathing.
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How long does ORENCIA usually take to work?
How long does ORENCIA usually take to work?
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Response in patients new to a biologic
15 days to 3 mos
If patients are new to biologic therapy, a response could be seen in as little as 15 days but may take up to 3 months.
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Response in patients previously treated with a biologic
4 to 6 wks, up to 4 mos
If patients have been previously treated with a biologic, a response could be seen within 4 to 6 weeks but may take up to 4 months.
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How often will I have to get these infusions?
How often will I have to get these infusions?
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1st infusion
2nd infusion at 2 wks
3rd infusion after another 2 wks
After patients receive their first infusion, they will have to get another one in 2 weeks, and then another 2 weeks after that.
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After 3rd infusion ...
Once every 4 weeks
Then, they only have to receive infusions every 4 weeks.
This concludes "Infusing ORENCIA IV," and I'd like to thank you for your valuable time and attention today. Please listen to the Important Safety Information, which follows.
If you have any questions about this material or would like to know more about ORENCIA IV, or ORENCIA support services, please call 1-800-ORENCIA. Or visit ORENCIA.com.
And finally, from all of us at Bristol-Myers Squibb, a special thank you for all that you do.
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Indication and Usage
Adult Rheumatoid Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.
Important Safety Information for ORENCIA® (abatacept)
Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, 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, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.
Indication and Usage
Adult Rheumatoid Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying anti rheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.
Important Safety Information for ORENCIA® (abatacept)
Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, 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, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.
[Superimposed]
Important Safety Information for ORENCIA® (abatacept) continued
Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. 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 treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.
Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. 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 treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.
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Important Safety Information for ORENCIA® (abatacept) continued
Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. 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. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.
Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. 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. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.
[Superimposed]
Important Safety Information for ORENCIA® (abatacept) continued
Immunizations: Prior to initiating ORENCIA in adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.
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 events more frequently than those treated with placebo (97% vs 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.
Immunizations: Prior to initiating ORENCIA in adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.
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 events more frequently than those treated with placebo (97% vs 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.
[Superimposed]
Important Safety Information for ORENCIA® (abatacept) continued
Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.
Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.
Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.
Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.
[Superimposed]
Important Safety Information for ORENCIA® (abatacept) continued
Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972.
Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.
Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972.
Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.
[Superimposed]
Important Safety Information for ORENCIA® (abatacept) continued
Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo).
Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.
Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies.
Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo).
Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.
Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies.
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Please see Full Prescribing Information
Please click here for Full Prescribing Information
Bristol Myers Squibb
© 2022 Bristol-Myers Squibb Company.
ORENCIA is a registered trademark of Bristol-Myers Squibb Company
427-US-2100916 Jan/22
Patients switching from ORENCIA IV to ORENCIA SC administration should take their first SC dose instead of their next scheduled IV dose.
BMI, body mass index; SC, subcutaneous.
ORENCIA showed comparable symptom improvement as an SC or IV formulation3
ACQUIRE was a 6-month, multinational, Phase IIIb study to compare the efficacy and safety of ORENCIA SC + MTX vs ORENCIA IV + MTX. The primary endpoint was noninferiority between ORENCIA SC and IV based on ACR 20 response at 6 months. ACR 50, ACR 70, safety, and immunogenicity at 6 months were also assessed.
Estimate of difference 0.2% (95% CI -4.2,4.8) supported noninferiority of ORENCIA SC based on a predefined margin of noninferiority of -7.5%.
ORENCIA SC and ORENCIA IV
ACR responses over 6 months3,4†11
ACR, American College of Rheumatology; CI, confidence interval; MTX, methotrexate.
†N values represent the per-protocol population.
Safety
ACQUIRE is one of the 7 clinical trials included in the Full Prescribing Information. The other 6 are included in the Pooled Safety information and ACQUIRE results at 6 months are consistent with the established safety profile. Please refer to the Pooled Safety and Full Prescribing Information.1,3
Study Design3
ORENCIA SC and ORENCIA IV
ACR responses over 6 months3,4*11
Inclusion Criteria3,4
- MTX-IR for ≥3 months
- Active RA (≥10 swollen joints, ≥12 tender joints)
- CRP ≥0.8 mg/dL
- Age ≥18 years
Baseline Characteristics3
In the ORENCIA SC arm, the average age was 49.9 years, HAQ-DI score was 1.7, and DAS28-CRP was 6.25. In the ORENCIA IV arm, the average age was 49.9 years, HAQ-DI score was 1.7, and DAS28-CRP was 6.22. Mean CRP level was 2.7 mg/dL in each group. Average disease duration was 7.6 years in the SC treatment group and 7.7 years in the IV treatment group. 85.1% of the SC treatment group and 86.5% of the IV treatment group were RF+.
Reference: ORENCIA [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
Indications and Usage
Adult Rheumatoid Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
Polyarticular Juvenile Idiopathic Arthritis: ORENCIA® (abatacept) is indicated for the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA).
Psoriatic Arthritis:
ORENCIA® (abatacept) is indicated for the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA).
Prophylaxis for Acute Graft versus Host Disease: ORENCIA® (abatacept) is indicated for the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), in adults and pediatric patients 2 years of age or older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated-donor.
Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.
Important Safety Information for ORENCIA® (abatacept)
Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult moderate to severe rheumatoid arthritis (RA) patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections
Hypersensitivity Reactions: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). 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 treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.
Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. 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. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.
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. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.
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. In the study, 97% of COPD patients treated with ORENCIA developed adverse events versus 88% treated with placebo. Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation
Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.
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. The range of time to onset of the event was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Before administering ORENCIA, provide recommended prophylaxis for EBV infection and continue for 6 months post-transplantation to prevent EBV-associated PTLD. Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7% (n=8) experienced CMV invasive diseases up to day 225 post-transplant. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract. 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 during treatment and for six months following HSCT.
Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.
Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling
Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.
Most Serious Adverse Reactions: In controlled clinical trials, adult RA patients experienced serious infections
Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.
Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of pJIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in pediatric pJIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients. The most frequent adverse reactions of all grades reported in ≥10% of patients with aGVHD who received ORENCIA with a difference of ≥2% for the 7/8 cohort, 8/8 cohort Orencia arm, and 8/8 cohort placebo arm, respectively, were anemia (56%, 69%, and 57%), CD4 lymphocytes decreased (14%, 14%, and 9%), hypertension (49%, 43%, and 38%), pyrexia (28%, 19%, and 20%), CMV reactivation/CMV infection (26%, 32%,and 22%), pneumonia (19%, 12%, and 10%), epistaxis (12%, 16%, and 10%), acute kidney injury (9%, 15%,and 10%), and hypermagnesemia (5%, 18%, 10%).
Incidence rates of grade 3 or 4 adverse reactions were the same as incidence rates of all grades, with the exception of grade 3 or 4 pyrexia in all arms (9% [7/8 cohort], 10% [8/8 cohort, ORENCIA arm], and 4% [8/8 cohort, placebo arm]), pneumonia in the 8/8 cohort placebo arm (9%) and acute kidney injury in the 7/8 cohort ORENCIA arm (7%). Clinically relevant adverse reactions in <10% of patients who received ORENCIA in combination with calcineurin inhibitor and methotrexate in Study GVHD-1 included EBV reactivation.
Note concerning ORENCIA administration options: ORENCIA may be administered as an intravenous infusion only for patients 6 years of age and older. PJIA or pediatric PsA patients may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determines it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested. ORENCIA for the prophylaxis of aGVHD in patients undergoing HSCT may only be administered as an intravenous (IV) infusion. The safety and effectiveness of ORENCIA have not been established in pediatric patients younger than 2 years of age for prophylaxis of aGVHD.
Indications and Usage
Adult Rheumatoid Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
Polyarticular Juvenile Idiopathic Arthritis: ORENCIA® (abatacept) is indicated for the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA).
Psoriatic Arthritis: ORENCIA® (abatacept) is indicated for the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA).
Prophylaxis for Acute Graft versus Host Disease: ORENCIA® (abatacept) is indicated for the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), in adults and pediatric patients 2 years of age or older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated-donor.
Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.
Important Safety Information for ORENCIA® (abatacept)
Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult moderate to severe rheumatoid arthritis (RA) patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections
Hypersensitivity Reactions: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). 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 treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.
Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. 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. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.
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. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.
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. In the study, 97% of COPD patients treated with ORENCIA developed adverse events versus 88% treated with placebo. Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.
Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.
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. The range of time to onset of the event was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Before administering ORENCIA, provide recommended prophylaxis for EBV infection and continue for 6 months post-transplantation to prevent EBV-associated PTLD. Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7% (n=8) experienced CMV invasive diseases up to day 225 post-transplant. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract. 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 during treatment and for six months following HSCT.
Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.
Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling
Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.
Most Serious Adverse Reactions: In controlled clinical trials, adult RA patients experienced serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo). In the GVHD-1 study, serious adverse reactions reported in >5% of patients who received ORENCIA in combination with a calcineurin inhibitor and methotrexate included pyrexia (20%), pneumonia (8%), acute kidney injury (7%), diarrhea (6%), hypoxia (5%), and nausea (5%).
Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.
Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of pJIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in pediatric pJIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients. The most frequent adverse reactions of all grades reported in ≥10% of patients with aGVHD who received ORENCIA with a difference of ≥2% for the 7/8 cohort, 8/8 cohort Orencia arm, and 8/8 cohort placebo arm, respectively, were anemia (56%, 69%, and 57%), CD4 lymphocytes decreased (14%, 14%, and 9%), hypertension (49%, 43%, and 38%), pyrexia (28%, 19%, and 20%), CMV reactivation/CMV infection (26%, 32%, and 22%), pneumonia (19%, 12%, and 10%), epistaxis (12%, 16%, and 10%), acute kidney injury (9%, 15%, and 10%), and hypermagnesemia (5%, 18%, 10%).
Incidence rates of grade 3 or 4 adverse reactions were the same as incidence rates of all grades, with the exception of grade 3 or 4 pyrexia in all arms (9% [7/8 cohort], 10% [8/8 cohort, ORENCIA arm], and 4% [8/8 cohort, placebo arm]), pneumonia in the 8/8 cohort placebo arm (9%) and acute kidney injury in the 7/8 cohort ORENCIA arm (7%). Clinically relevant adverse reactions in <10% of patients who received ORENCIA in combination with calcineurin inhibitor and methotrexate in Study GVHD-1 included EBV reactivation.
Note concerning ORENCIA administration options: ORENCIA may be administered as an intravenous infusion only for patients 6 years of age and older. PJIA or pediatric PsA patients may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determines it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested. ORENCIA for the prophylaxis of aGVHD in patients undergoing HSCT may only be administered as an intravenous (IV) infusion. The safety and effectiveness of ORENCIA have not been established in pediatric patients younger than 2 years of age for prophylaxis of aGVHD.