CLASSES
Other Specific Antirheumatics
T-Cell Costimulation Blockers
DESCRIPTION
Human recombinant fusion protein; a co-stimulatory or second-signal blocker of T cell activation
Used for moderate to severe rheumatoid arthritis and active psoriatic arthritis in adults, moderately to severely active polyarticular juvenile idiopathic arthritis in children 2 years and older, and as prophylaxis of acute graft versus host disease, in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem-cell transplantation from a matched or 1 allele-mismatched unrelated donor
May increase risk for serious infection
COMMON BRAND NAMES
Orencia, Orencia ClickJect
HOW SUPPLIED
Orencia Intravenous Inj Pwd F/Sol: 250mg
Orencia Subcutaneous Inj Sol: 0.4mL, 0.7mL, 1mL, 50mg, 87.5mg, 125mg
DOSAGE & INDICATIONS
For the treatment of moderately to severely active rheumatoid arthritis.
Intravenous dosage
Adults weighing more than 100 kg
1,000 mg IV every 2 weeks for 3 doses, then 1,000 mg IV every 4 weeks. Guidelines suggest adding or switching to an anti-TNF biologic, abatacept, or rituximab for patients with established disease and moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. Switching to a non-TNF biologic such as abatacept for patients who have a serious adverse event with a TNF blocker is recommended. Further, a switch to a non-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to another non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of rituximab or with a non-serious adverse event to the drug. Lastly, a switch to another type or category of non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of the new drug. The goal is low disease activity or remission.
Adults weighing 60 to 100 kg
750 mg IV every 2 weeks for 3 doses, then 750 mg IV every 4 weeks. Guidelines suggest adding or switching to an anti-TNF biologic, abatacept, or rituximab for patients with established disease and moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. Switching to a non-TNF biologic such as abatacept for patients who have a serious adverse event with a TNF blocker is recommended. Further, a switch to a non-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to another non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of rituximab or with a non-serious adverse event to the drug. Lastly, a switch to another type or category of non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of the new drug. The goal is low disease activity or remission.
Adults weighing less than 60 kg
500 mg IV every 2 weeks for 3 doses, then 500 mg IV every 4 weeks. Guidelines suggest adding or switching to an anti-TNF biologic, abatacept, or rituximab for patients with established disease and moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. Switching to a non-TNF biologic such as abatacept for patients who have a serious adverse event with a TNF blocker is recommended. Further, a switch to a non-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to another non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of rituximab or with a non-serious adverse event to the drug. Lastly, a switch to another type or category of non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of the new drug. The goal is low disease activity or remission.
Subcutaneous dosage
Adults
125 mg subcutaneously once weekly; may be given with or without IV loading dose. If IV loading dose is used, administer the first subcutaneous injection within 1 day of the infusion; for persons switching from IV to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled IV dose. Guidelines suggest adding or switching to an anti-TNF biologic, abatacept, or rituximab for patients with established disease and moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. Switching to a non-TNF biologic such as abatacept for patients who have a serious adverse event with a TNF blocker is recommended. Further, a switch to a non-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to another non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of rituximab or with a non-serious adverse event to the drug. Lastly, a switch to another type or category of non-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of the new drug. The goal is low disease activity or remission.
For the treatment of moderate to severe polyarticular juvenile idiopathic arthritis as monotherapy or with methotrexate to reduce signs and symptoms of the disease.
Subcutaneous dosage
Children and Adolescents 2 years and older and weighing 50 kg or more
125 mg subcutaneously once weekly.
Children and Adolescents 2 years and older and weighing 25 kg to less than 50 kg
87.5 mg subcutaneously once weekly.
Children and Adolescents 2 years and older and weighing 10 kg to less than 25 kg
50 mg subcutaneously once weekly.
Intravenous dosage
Children and Adolescents 6 years and older and weighing more than 100 kg
1000 mg IV infusion over 30 minutes every 2 weeks for 3 doses (i.e., a dose at weeks 0, 2, and 4). Starting at week 8, give 1000 mg IV infusion over 30 minutes every 4 weeks. Determine the patient’s body weight before each dose.
Children and Adolescents 6 years and older and weighing 75 to 100 kg
750 mg IV infusion over 30 minutes every 2 weeks for 3 doses (i.e., a dose at weeks 0, 2, and 4). Starting at week 8, give 750 mg IV infusion over 30 minutes every 4 weeks. Determine the patient’s body weight before each dose.
Children and Adolescents 6 years and older and weighing less than 75 kg
10 mg/kg IV infusion over 30 minutes every 2 weeks for 3 doses (i.e., a dose at weeks 0, 2, and 4). Starting at week 8, give 10 mg/kg IV infusion over 30 minutes every 4 weeks. Determine the patient’s body weight before each dose.
For the treatment active psoriatic arthritis in adult patients.
Intravenous dosage
Adults weighing more than 100 kg
1000 mg IV infusion over 30 minutes every 2 weeks for 3 doses (i.e., doses at weeks 0, 2, and 4). Starting at week 8, give 1000 mg IV infusion over 30 minutes every 4 weeks. Abatacept may be administered with or without non-biologic DMARDs (disease-modifying antirheumatic drugs).
Adults weighing 60 to 100 kg
750 mg IV infusion over 30 minutes every 2 weeks for 3 doses (i.e., doses at weeks 0, 2, and 4). Starting at week 8, give 750 mg IV infusion over 30 minutes every 4 weeks. Abatacept may be administered with or without non-biologic DMARDs (disease-modifying antirheumatic drugs).
Adults weighing less than 60 kg
500 mg IV infusion over 30 minutes every 2 weeks for 3 doses (i.e., doses at weeks 0, 2, and 4). Starting at week 8, give 500 mg IV infusion over 30 minutes every 4 weeks. Abatacept may be administered with or without non-biologic DMARDs (disease-modifying antirheumatic drugs).
Subcutaneous dosage
Adults
125 mg subcutaneously once weekly. No intravenous loading dose is needed. Patients switching from intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose. Abatacept may be administered with or without non-biologic DMARDs (disease-modifying antirheumatic drugs).
For acute graft-versus-host disease (GVHD) prophylaxis in patients undergoing hematopoietic stem-cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor, in combination with a calcineurin inhibitor and methotrexate.
NOTE: Abatacept has been designated an orphan drug by the FDA for the prevention of GVHD.
Intravenous dosage
Adults
10 mg/kg (maximum dose of 1,000 mg) IV for 4 doses given on day -1 (day before transplantation) and days 5, 14, and 28 after transplantation, in combination with a calcineurin inhibitor and methotrexate. Begin prophylactic therapy for Epstein-Barr virus reactivation prior to starting abatacept and consider prophylactic therapy for cytomegalovirus infection/reactivation during therapy; continue prophylaxis for 6 months post-transplantation. The addition of abatacept to a calcineurin inhibitor (i.e., cyclosporine or tacrolimus) and methotrexate as prophylaxis of acute GVHD was evaluated in patients aged 6 years and older who underwent HSCT from a matched (n = 73; median age, 44 years; range, 6 to 71 years) or 1 allele mismatched (n = 43; median age, 38 years; range, 6 to 77 years) unrelated donor in a multicenter, 2-cohort, phase 2 trial (the ABA2 trial). All patients received myeloablative therapy prior to allogeneic HSCT. Calcineurin inhibitor therapy, consisting of either cyclosporine (adjusted to maintain a level of 100 to 300 nanograms/mL) or tacrolimus (adjusted to maintain a level of 5 to 15 nanograms/mL), was started at least 36 hours before the stem-cell infusion and continued through post-transplant day 100 (tapered between post-transplant days 100 and 180). All patients received methotrexate 15 mg/m2 IV on post-transplant day 1 (starting 24 hours from the completion of the stem-cell infusion) and 10 mg/m2 IV on post-transplant days 3, 6, and 11. Grade 3 or 4 acute GVHD was not significantly improved at post-transplant day 100 (primary endpoint) or day 180 with abatacept prophylaxis compared with placebo in patients with matched donors who were included in the randomized, double-blind study cohort; additionally, the severe acute GVHD-free survival at post-transplant day 180 was not significantly improved with abatacept (87% vs. 75%; hazard ratio (HR) = 0.55; 95% CI, 0.26 to 1.18). In these patients, post-transplant 180-day grades 2 to 4 acute GVHD-free survival (50% vs. 32%; HR = 0.54; 95% CI, 0.35 to 0.83) and overall survival (97% vs. 84%; HR = 0.33; 95% CI, 0.12 to 0.93) rates were significantly improved with abatacept prophylaxis compared with placebo. In patients with 1 allele mismatched donors who received abatacept prophylaxis in the single-arm study cohort, the post-transplant 180-day grade 3 or 4 acute GVHD-free survival, grades 2 to 4 acute GVHD-free survival, and overall survival rates were 95%, 53%, and 98%, respectively. In patients with 1 allele mismatched donors, the post-transplant 180-day OS rate was 98% in 54 patients who received abatacept plus a calcineurin inhibitor and methotrexate and 75% in 162 control cohort patients who received a calcineurin inhibitor and methotrexate only from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry.
Children 6 years and older and Adolescents
10 mg/kg (maximum dose of 1,000 mg) IV for 4 doses given on day -1 (day before transplantation) and days 5, 14, and 28 after transplantation, in combination with a calcineurin inhibitor and methotrexate. Begin prophylactic therapy for Epstein-Barr virus reactivation prior to starting abatacept and consider prophylactic therapy for cytomegalovirus infection/reactivation during therapy; continue prophylaxis for 6 months post-transplantation. The addition of abatacept to a calcineurin inhibitor (i.e., cyclosporine or tacrolimus) and methotrexate as prophylaxis of acute GVHD was evaluated in patients aged 6 years and older who underwent HSCT from a matched (n = 73; median age, 44 years; range, 6 to 71 years) or 1 allele mismatched (n = 43; median age, 38 years; range, 6 to 77 years) unrelated donor in a multicenter, 2-cohort, phase 2 trial (the ABA2 trial). All patients received myeloablative therapy prior to allogeneic HSCT. Calcineurin inhibitor therapy, consisting of either cyclosporine (adjusted to maintain a level of 100 to 300 nanograms/mL) or tacrolimus (adjusted to maintain a level of 5 to 15 nanograms/mL), was started at least 36 hours before the stem-cell infusion and continued through post-transplant day 100 (tapered between post-transplant days 100 and 180). All patients received methotrexate 15 mg/m2 IV on post-transplant day 1 (starting 24 hours from the completion of the stem-cell infusion) and 10 mg/m2 IV on post-transplant days 3, 6, and 11. Grade 3 or 4 acute GVHD was not significantly improved at post-transplant day 100 (primary endpoint) or day 180 with abatacept prophylaxis compared with placebo in patients with matched donors who were included in the randomized, double-blind study cohort; additionally, the severe acute GVHD-free survival at post-transplant day 180 was not significantly improved with abatacept (87% vs. 75%; hazard ratio (HR) = 0.55; 95% CI, 0.26 to 1.18). In these patients, post-transplant 180-day grades 2 to 4 acute GVHD-free survival (50% vs. 32%; HR = 0.54; 95% CI, 0.35 to 0.83) and overall survival (97% vs. 84%; HR = 0.33; 95% CI, 0.12 to 0.93) rates were significantly improved with abatacept prophylaxis compared with placebo. In patients with 1 allele mismatched donors who received abatacept prophylaxis in the single-arm study cohort, the post-transplant 180-day grade 3 or 4 acute GVHD-free survival, grades 2 to 4 acute GVHD-free survival, and overall survival rates were 95%, 53%, and 98%, respectively. In patients with 1 allele mismatched donors, the post-transplant 180-day OS rate was 98% in 54 patients who received abatacept plus a calcineurin inhibitor and methotrexate and 75% in 162 control cohort patients who received a calcineurin inhibitor and methotrexate only from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry.
Children 2 years to less than 6 years old
15 mg/kg IV on day -1 (day before transplantation) followed by 12 mg/kg IV on days 5, 14, and 28 after transplantation for a total of 4 doses, in combination with a calcineurin inhibitor and methotrexate. Begin prophylactic therapy for Epstein-Barr virus reactivation prior to starting abatacept and consider prophylactic therapy for cytomegalovirus infection/reactivation during therapy; continue prophylaxis for 6 months post-transplantation. Efficacy for pediatric patients aged 2 years to less than 6 years old was extrapolated from pharmacokinetic modeling and simulation data and studies in adults and pediatric patients aged 6 years and older.
MAXIMUM DOSAGE
Adults
Rheumatoid arthritis (RA) or Psoriatic Arthritis (PsA)
125 mg per week subcutaneously
OR
Weight more than 100 kg: 1,000 mg IV
Weight 60 to 100 kg: 750 mg IV
Weight less than 60 kg: 500 mg IV
Acute graft-versus-host disease (aGVHD) prophylaxis:
10 mg/kg (Max: 1,000 mg) IV
Geriatric
Rheumatoid arthritis (RA) or Psoriatic Arthritis (PsA)
125 mg per week subcutaneously
OR
Weight more than 100 kg: 1,000 mg IV
Weight 60 to 100 kg: 750 mg IV
Weight less than 60 kg: 500 mg IV
Acute graft-versus-host disease (aGVHD) prophylaxis:
10 mg/kg (Max: 1,000 mg) IV
Adolescents
Polyarticular juvenile idiopathic arthritis (pJIA)
Weight 50 kg or more: 125 mg per week subcutaneously
Weight 25 kg to less than 50 kg: 87.5 mg per week subcutaneously
Weight 10 kg to less than 25 kg: 50 mg per week subcutaneously
OR
Weight more than 100 kg: 1,000 mg IV
Weight 75 kg to 100 kg: 750 mg IV
Weight less than 75 kg: 10 mg/kg IV
aGVHD prophylaxis
10 mg/kg (Max: 1,000 mg) IV.
Children
Polyarticular juvenile idiopathic arthritis (pJIA)
2 years and older:
Weight 50 kg or more: 125 mg per week subcutaneously
Weight 25 kg to less than 50 kg: 87.5 mg per week subcutaneously
Weight 10 kg to less than 25 kg: 50 mg per week subcutaneously
Safety and efficacy of subcutaneous use have not been established in children less than 2 years of age.
6 years and older:
Weight more than 100 kg: 1,000 mg IV
Weight 75 kg to 100 kg: 750 mg IV
Weight less than 75 kg: 10 mg/kg IV
Safety and efficacy of IV use have not been established in children less than 6 years of age.
aGVHD prophylaxis
6 years and older: 10 mg/kg (Max: 1,000 mg) IV.
2 years to less than 6 years: 15 mg/kg IV (first dose); 12 mg/kg IV (second, third, and fourth dose).
Safety and efficacy for aGVHD prophylaxis have not been established in children less than 2 years of age.
Infants
Use not established.
Neonates
Use not established.
DOSING CONSIDERATIONS
Hepatic Impairment
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
ADMINISTRATION
Injectable Administration
The single-dose prefilled syringes and the prefilled ClickJect autoinjector are for subcutaneous injection only.
The 250 mg, single-use vial of lyophilized powder is for dilution and use for intravenous infusion only.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The liquid should be clear and colorless to pale yellow. Do not inject abatacept if the liquid is cloudy, discolored, or has lumps or particles in it.
Intravenous Administration
Administer as an intravenous infusion after preparation as directed. Do not give as an IV push or bolus. Only the vials are used to prepare the intravenous infusion; do not use the prefilled syringe or ClickJect autoinjector for this purpose.
Only administer in a hospital or clinic setting with full resuscitation equipment and under the supervision of a physician experienced with the administration of biologic therapies. Appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction.
Reconstitution of abatacept vials:
Determine the number of vials needed. Each vial contains 250 mg of abatacept.
Remove the flip-top from the vial and wipe the top with an alcohol swab.
Use a silicone-free disposable syringe with an 18 to 21 gauge needle to reconstitute each vial with 10 mL of Sterile Water for Injection. If a siliconized syringe is used, the solution may develop a few translucent particles; discard any solutions prepared using siliconized syringes. Additional silicone-free, disposable syringes can be obtained by calling 800-673-6242.
Insert the syringe needle into the vial and direct the stream to the glass wall of the vial. Do not use the vial if the vacuum is not present. Gently swirl the solution by rotating the vial to dissolve the powder. Avoid prolonged or vigorous agitation. Do not shake.
The solution should be clear and colorless to pale yellow. Do not use if opaque particles, discoloration, or other foreign particles are present.
Once all the powder is dissolved, vent the vial with a needle to dissipate any foam that may be present. After reconstitution, the concentration of the solution in the vial is 25 mg/mL of abatacept.
Preparation of intravenous infusion:
Further dilute the required dose of the reconstituted vial solution to 100 mL with 0.9% Sodium Chloride Injection. Withdraw a volume of 0.9% Sodium Chloride Injection equal to the volume of the reconstituted abatacept vials from a 100 mL bag or bottle containing 0.9% Sodium Chloride Injection. For example, for 2 vials, remove 20 mL of 0.9% Sodium Chloride Injection.
Slowly add the reconstituted abatacept solution from each vial into the infusion bag or bottle using the same silicone-free, disposable syringe. Gently mix.
Final concentration of the diluted infusion is dependent on the abatacept dose but will be no more than 10 mg/mL. For example, the concentration of the fully diluted abatacept solution in the infusion bag or bottle will be approximately 5 mg/mL if 2 vials of abatacept are used (500 mg/100 mL).
Abatacept vials do not contain preservatives. Immediately discard any unused portion.
Storage: Fully diluted infusion solution may be stored at room temperature or refrigerated at 2 to 8 degrees C (36 to 46 degrees F) before use, but the infusion must be completed within 24 hours of reconstitution of the drug vials.
Intravenous infusion administration:
If visibly opaque particles, discoloration, or other foreign particles are observed, do not use the infusion solution.
Administer as an IV infusion over 30 minutes in patients with arthritis and over 60 minutes in patients receiving abatacept for acute graft versus host disease prophylaxis.
Use an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (pore size of 0.2 to 1.2 microns).
Do not infuse abatacept concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of abatacept with other agents.
The infusion must be completed within 24 hours of reconstitution of the drug vials. Any unused portion should not be stored for reuse.
Subcutaneous Administration
Only an individual trained in subcutaneous drug delivery should administer the injection. A patient who is properly trained in injection technique may self-inject if the action is deemed appropriate.
Prefilled syringe
The prefilled syringe is for subcutaneous administration only; do not administer intravenously.
Remove 1 single-use prefilled syringe from the refrigerator about 30 to 60 minutes before use to allow it to reach room temperature. Do not speed up the warming process in any way. For example, do not use the microwave or place the syringe in warm water.
The amount of liquid should be between the 2 lines on the syringe barrel. Do not use the syringe if more or less liquid is in the syringe.
Acceptable subcutaneous injection sites are the front of the thighs, the outer area of the upper arms, or the abdomen except for the 2-inch area around the navel. Do not inject tender, bruised, red, scaly, hard, stretched, or scarred skin.
Gently pinch the cleaned skin area and hold firmly. Insert the needle at a 45 degree angle using a quick, dart-like motion. Inject the full amount in the prefilled syringe.
Rotate injection sites. The same area of the body may be used for weekly injections but use a different injection site at least 1 inch away from the last area injected.
ClickJect autoinjector
The ClickJect autoinjector (125 mg/mL) is for subcutaneous administration only; do not administer intravenously.
The ClickJect autoinjector should not be used in pediatric patients under the age of 18 years.
Remove 1 autoinjector from the refrigerator about 30 minutes before use to allow it to reach room temperature. Do not remove the autoinjector needle cover while allowing it to reach room temperature.
Do not use if autoinjector is cracked or damaged or if the expiration date has passed.
Check the liquid through the viewing window. It should be clear and colorless to pale yellow. A small air bubble may be seen; it does not have to be removed. Do not inject if the liquid is cloudy, discolored, or has particles.
Pull the orange needle cover straight off. Do not recap.
Position autoinjector so the viewing window is visible and at a 90 degree angle to the injection site. With the other hand, gently pinch cleaned skin.
Acceptable subcutaneous injection sites are the front of the thighs, the outer area of the upper arms, or the abdomen except for the 2-inch area around the navel. Do not inject tender, bruised, red, scaly, hard, stretched, or scarred skin.
Push down on skin to unlock autoinjector. Press button and hold for 15 seconds and watch the window. A click will be heard as the injection begins. Keep holding the button until the blue indicator stops moving in the window.
Remove the autoinjector from the injection site by lifting straight up; the transparent tip will lock over the needle.
Rotate injection sites. The same area of the body may be used for weekly injections but use a different injection site at least 1 inch away from the last area injected.
STORAGE
Orencia:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Do not freeze
- Prior to dispensing, store in refrigerator (36 to 46 degrees F)
- Protect from light
- See package insert for detailed storage information
- Store in original package until time of use
Orencia ClickJect :
- Discard product if it contains particulate matter, is cloudy, or discolored
- Do not freeze
- Protect from light
- Refrigerate (between 36 and 46 degrees F)
- Store in original package until time of use
CONTRAINDICATIONS / PRECAUTIONS
Angioedema, maltose hypersensitivity, serious hypersensitivity reactions or anaphylaxis
Serious hypersensitivity reactions or anaphylaxis have occurred with use of abatacept during clinical trials and postmarketing. In postmarketing experience, fatal anaphylaxis following the first infusion of the drug and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose, 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 abatacept should be stopped immediately with appropriate therapy instituted, and the use of abatacept should be permanently discontinued. Abatacept lyophilized powder for intravenous infusion preparation contains maltose, so this dosage form should not be used in patients with maltose hypersensitivity; the subcutaneous injection solutions do not contain maltose.
Hepatitis, hepatitis B exacerbation, immunosuppression, infection, tuberculosis
Abatacept is associated with an increased risk of developing serious infections, such as sepsis and respiratory infections (e.g., pneumonia). Serious, and sometimes fatal, infections have developed in abatacept recipients, with many occurring in patients receiving concomitant immunosuppressive therapies. Use caution when considering the use of abatacept in patients with a history of recurrent infections, underlying immunosuppression, or conditions that may predispose them to infections, or patients with pre-existing chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with this drug should be monitored closely. Administration of abatacept should be discontinued if a patient develops a serious infection. Prior to initiation of abatacept therapy, evaluate patients for tuberculosis risk factors and for active or latent tuberculosis infection with a tuberculin skin test. The drug has not been studied in patients with a positive tuberculosis screen and the safety of abatacept receipt by patients with latent tuberculosis infection is unknown. Patients with a positive tuberculosis test should be treated by standard medical practice before the use of abatacept. Also, screen patients for viral hepatitis in accordance with published guidelines before starting abatacept, as anti-rheumatic therapies have been associated with hepatitis B reactivation, which may lead to hepatitis B exacerbation. Patients who screened positive for hepatitis were excluded from clinical trials. Patients who develop a new infection during therapy should be closely monitored. If a patient develops a serious infection during abatacept therapy, the drug should be discontinued. Due to an increased risk for infection and a lack of confirmed additional benefit, inform patients that the concomitant use of abatacept with other immunosuppressives (e.g., biologic DMARDs such as TNF inhibitors, JAK inhibitors) is not recommended.
Chronic obstructive pulmonary disease (COPD)
Use abatacept with caution in patients with chronic obstructive pulmonary disease (COPD). In a rheumatoid arthritis study, patients with COPD who received abatacept experienced a higher incidence of adverse respiratory disorders, such as COPD exacerbation, cough, rhonchi, and dyspnea, compared to patients who received placebo. Abatacept patients were also more likely to experience a serious adverse event compared to placebo patients. If abatacept therapy is given to a patient with COPD, the patient should be monitored for worsening of their respiratory status.[31761]
New primary malignancy, skin cancer
The possibility exists for drugs inhibiting T cell activation, including abatacept, to affect host defenses against malignancies since T cells mediate cellular immune responses. The impact of abatacept therapy on the development of a new primary malignancy and course of malignancies is not fully understood. Malignancies, including skin cancer, have been reported with abatacept therapy. Periodic skin examinations are recommended for all patients treated with abatacept, especially those with risk factors for skin cancer.
Vaccination
Prior to initiating abatacept in pediatric and adult patients, be sure to update vaccination in accordance with current immunization guidelines. Abatacept-treated patients may receive current non-live vaccines. Live vaccines should not be given concurrently with abatacept therapy or within 3 months after discontinuation. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving abatacept. Based on its mechanism of action, this drug may blunt the effectiveness of some immunizations.
Geriatric
Caution should be utilized when treating geriatric patients with abatacept therapy due to a higher incidence of serious infections and malignancies. In clinical trials, the frequency of serious infection and malignancy among abatacept-treated patients over 65 years of age was higher than for those under age 65. There were no other overall differences in safety and efficacy observed between geriatric (patients 65 years of age and older) and younger adults in clinical trials.
Infants, neonates, pregnancy
Data with abatacept use during human pregnancy are insufficient to inform a drug-associated risk. There are no adequate and well-controlled studies in pregnant women. It is unknown if abatacept can cross the placenta into the fetus when a woman is treated with abatacept during pregnancy. Experts state that abatacept has limited documentation on safe use in pregnancy and should be replaced before conception by other medication if possible. In studies involving pregnant rats and rabbits, no teratogenic effects were observed at doses 29 times the maximum recommended human dose (MRHD). However, in a pre- and post-natal development study in rats, abatacept altered immune function in female offspring at 11 times the MRHD. There were no adverse effects observed at approximately 3 times the MRHD. In the juvenile rat, which may be more representative of the fetal immune system state in humans, abatacept exposure resulted in immune system abnormalities including inflammation of the thyroid and pancreas. Since abatacept is an immunomodulatory agent, the safety of administering live vaccines in neonates and infants exposed in utero to abatacept is unknown and the risk and benefits should be considered prior to vaccinating such infants. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to abatacept; information about the registry can be obtained at mothertobaby.org/ongoing-study/orencia or by calling 1-877-311-8972.
Breast-feeding
There is no data regarding the presence of abatacept in human milk, the effects on the breast-feeding infant, or the effects on milk production. Abatacept was detected in the milk of lactating rats. Until more data are available, experts state that abatacept use should be avoided during lactation if other therapy is available to control the disease. However, in general, lactation should not be discouraged if no other options to abatacept are available, since the oral absorption of the drug by an infant is likely to be low due to poor bioavailability.
Children
Safety and efficacy of subcutaneous abatacept have not been studied in infants and children less than 2 years of age. Intravenous abatacept has not been in pediatric patients younger than 6 years of age. Similar to adults, pediatric patients treated with this medication may be at an increased risk of infection and have a decreased response to immunizations. If possible, administer all needed vaccinations to patients before abatacept initiation.
Diabetes mellitus, laboratory test interference
An important laboratory test interference has been reported with abatacept intravenous infusion. Parenteral drug products containing maltose can interfere with the readings of blood glucose monitors that use test strips with glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). The GDH-PQQ based glucose monitoring systems may react with the maltose present in abatacept for intravenous administration, resulting in falsely elevated blood glucose readings on the day of infusion. When receiving intravenous abatacept, patients with diabetes mellitus that require blood glucose monitoring should be advised to consider methods 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. This interference does not apply to subcutaneous abatacept therapy; the subcutaneous injection solution does not contain maltose.
Post-transplant lymphoproliferative disorder (PTLD)
Invasive cytomegalovirus (CMV) infection and post-transplant lymphoproliferative disorder (PTLD) associated with Epstein-Barr virus (EBV) infection have been reported in patients who were undergoing an unrelated allogeneic stem-cell transplant and received abatacept prophylaxis for acute GVHD. Evaluate EBV serology status at baseline; monitor for EBV reactivation after transplantation. Begin prophylactic therapy for EBV prior to starting abatacept and for 6 months post-transplantation. Evaluate CMV serology status at baseline; consider prophylactic therapy for CMV during therapy and for 6 months post-transplantation.
ADVERSE REACTIONS
Severe
anemia / Delayed / 0-69.0
hypertension / Early / 0-49.0
infection / Delayed / 0-19.0
hypermagnesemia / Delayed / 0-18.0
epistaxis / Delayed / 0-16.0
nephrotoxicity / Delayed / 0-15.0
lymphopenia / Delayed / 0-14.0
fever / Early / 0-10.0
post-transplant lymphoproliferative disorder (PTLD) / Delayed / 3.4-3.4
new primary malignancy / Delayed / 1.3-1.3
anaphylactic shock / Rapid / 0-0.1
anaphylactoid reactions / Rapid / 0-0.1
angioedema / Rapid / Incidence not known
vasculitis / Delayed / Incidence not known
skin cancer / Delayed / Incidence not known
Moderate
antibody formation / Delayed / 1.1-10.0
infusion-related reactions / Rapid / 2.0-9.0
hematoma / Early / 0-2.6
erythema / Early / 0-2.6
dyspnea / Early / 0-1.0
wheezing / Rapid / 0-1.0
hypotension / Rapid / 0.1-1.0
psoriasis / Delayed / Incidence not known
Mild
headache / Early / 1.0-18.0
sinusitis / Delayed / 5.0-13.0
influenza / Delayed / 5.0-13.0
pharyngitis / Delayed / 5.0-13.0
dizziness / Early / 1.0-9.0
cough / Delayed / 5.0-8.0
back pain / Delayed / 7.0-7.0
dyspepsia / Early / 6.0-6.0
rhinitis / Early / 0-5.0
injection site reaction / Rapid / 2.6-4.4
rash / Early / 0-4.0
musculoskeletal pain / Early / 3.0-3.0
pruritus / Rapid / 0-2.6
flushing / Rapid / 0-1.0
urticaria / Rapid / 0-1.0
abdominal pain / Early / 5.0
diarrhea / Early / 5.0
nausea / Early / 5.0
DRUG INTERACTIONS
Adalimumab: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Anakinra: (Major) Concomitant use of abatacept with biological DMARDs, such as anakinra, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with anakinra.
Antithymocyte Globulin: (Moderate) Concomitant use of immunosuppressives may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Atropine: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system.
Atropine; Difenoxin: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system.
Atropine; Edrophonium: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system.
Azathioprine: (Moderate) Concomitant use of immunosuppressives may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as abatacept, is not recommended because of the possibility of additive immunosuppression and increased infection risk. There is insufficient experience to assess the safety and efficacy of this combination. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Basiliximab: (Moderate) Concomitant use of immunosuppressives may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Canakinumab: (Major) Concomitant use of abatacept with biological DMARDs, such as canakinumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with canakinumab.
Certolizumab pegol: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Corticosteroids: (Moderate) Concomitant use of immunosuppressives, as well as long-term corticosteroids, may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Cyclophosphamide: (Moderate) Concomitant use of immunosuppressives such as cyclophosphamide may increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Cyclosporine: (Moderate) Concomitant use of immunosuppressives may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Diphenoxylate; Atropine: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system.
Etanercept: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Golimumab: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Guselkumab: (Major) Concomitant use of abatacept with other biologic agents, such as guselkumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with guselkumab.
Infliximab: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Ixekizumab: (Major) Concomitant use of abatacept with other biologic agents, such as ixekizumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with ixekizumab.
Live Vaccines: (Contraindicated) If possible, administer all needed vaccines before abatacept initiation. Live vaccines should not be given concurrently with abatacept or within 3 months of its discontinuation. The immune response of the immunocompromised patient to vaccines may be decreased and adjusted doses or boosters that are more frequent may be required. The immune response to an inactive vaccine may still be suboptimal. Live virus vaccines may induce the illness they are intended to prevent and are contraindicated for use during immunosuppressive treatment. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system. (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as scopolamine, have been shown to be capable of depressing the mucociliary transport system.
Rituximab: (Major) Avoid the concomitant use of rituximab and abatacept; coadministration may result in additive immunosuppression and an increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with other biologic therapy, such as rituximab, and therefore such use is not recommended.
Rituximab; Hyaluronidase: (Major) Avoid the concomitant use of rituximab and abatacept; coadministration may result in additive immunosuppression and an increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with other biologic therapy, such as rituximab, and therefore such use is not recommended.
Sarilumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, including selective costimulation modulators such as abatacept; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Scopolamine: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as scopolamine, have been shown to be capable of depressing the mucociliary transport system.
Secukinumab: (Major) Concomitant use of abatacept with biological DMARDs, such as secukinumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with secukinumab.
Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with biological DMARDs, including selective costimulation modulators such as abatacept; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as abatacept, is not recommended because of the possibility of additive immunosuppression and increased infection risk. There is insufficient experience to assess the safety and efficacy of this combination. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Tumor Necrosis Factor modifiers: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as abatacept, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Ustekinumab: (Major) Concomitant use of abatacept with biological DMARDs, such as ustekinumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with ustekinumab.
PREGNANCY AND LACTATION
Pregnancy
Data with abatacept use during human pregnancy are insufficient to inform a drug-associated risk. There are no adequate and well-controlled studies in pregnant women. It is unknown if abatacept can cross the placenta into the fetus when a woman is treated with abatacept during pregnancy. Experts state that abatacept has limited documentation on safe use in pregnancy and should be replaced before conception by other medication if possible. In studies involving pregnant rats and rabbits, no teratogenic effects were observed at doses 29 times the maximum recommended human dose (MRHD). However, in a pre- and post-natal development study in rats, abatacept altered immune function in female offspring at 11 times the MRHD. There were no adverse effects observed at approximately 3 times the MRHD. In the juvenile rat, which may be more representative of the fetal immune system state in humans, abatacept exposure resulted in immune system abnormalities including inflammation of the thyroid and pancreas. Since abatacept is an immunomodulatory agent, the safety of administering live vaccines in neonates and infants exposed in utero to abatacept is unknown and the risk and benefits should be considered prior to vaccinating such infants. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to abatacept; information about the registry can be obtained at mothertobaby.org/ongoing-study/orencia or by calling 1-877-311-8972.
MECHANISM OF ACTION
Mechanism of Action: Complete T cell activation requires two distinct signals. The first signal is the engagement of a T cell receptor with a MHC (major histocompatability complex)-peptide complex on the surface of an antigen-presenting cell (APC). The second signal is delivered by the binding of a costimulatory receptor on T cells to a ligand on the APC. The costimulatory signal is provided by the interaction of CD28 on T cells with the CD80 (B7-1) or CD86 (B7-2) ligand on APCs. If both signals are executed, the T cell reaches optimal activation and will proliferate and produce cytokines that can activate other inflammatory cells, such as macrophages. If only the first of two signals is satisfied, T cell activation is suboptimal rendering the T cell poorly responsive and may lead to cell death.Following optimal T cell activation, cytotoxic T-lymphocyte associated antigen (CTLA4) is expressed on the cell surface. Expression of CTLA4 causes T cell activation to cease. Binding of CTLA4 to both CD80 and CD86 prevents the interaction between CD28 and CD80/CD86, as the affinity of CTLA4 for CD80/CD86 is 500—2500 times greater than the affinity of CD28 for CD80/CD86.Abatacept (CTLA4-Ig) is a fusion protein that comprises the extracellular domain of human CTLA4 and a fragment of the Fc domain of human IgG1. Abatacept mimics endogenous CTLA4 and competes with CD28 for CD80 and CD86 binding. By blocking the engagement of CD28, CTLA4-Ig prevents the delivery of the second costimulatory signal that is required for optimal T cell activation. In vitro, abatacept decreases T cell proliferation and inhibits the production of several cytokines such as tumor necrosis factor alpha (TNF-alpha), interferon-gamma, and interleukin-2. In vivo, serum concentrations of soluble interleukin-2 receptor, interleukin-6, rheumatoid factor, C-reactive protein, matrix metalloproteinase-3, and TNF-alpha were decreased in patients with rheumatoid arthritis who received abatacept in clinical trials. The relationship between these biological response markers and the mechanism(s) of abatacept to control rheumatoid arthritis is unknown. Modulation of T cell activation would be expected to favorably affect multiple mechanisms of inflammation and progressive joint destruction, including secretion of pro-inflammatory cytokines, proliferation of inflammatory cells, and production of autoantibodies. Also, as T cells mediate cellular immune responses, abatacept may affect host defenses against infections and malignancies (see Adverse Reactions).
PHARMACOKINETICS
Abatacept is administered intravenously (IV) or subcutaneously. After subcutaneous administration, the mean estimate for systemic clearance was 0.28 mL/kg/hour, and the mean estimate for terminal half-life was 14.3 days in patients with rheumatoid arthritis (RA). Comparable numbers were obtained after IV administration: mean half-life of 13.1 days, and mean clearance of 0.22 mL/kg/hour. Concomitant medication such as methotrexate, corticosteroids, and NSAIDs did not influence abatacept apparent clearance in patients with RA receiving subcutaneous abatacept.
Following the first abatacept 10 mg/kg IV infusion dose for the prevention of acute GVHD, the steady-state volume of distribution values were 0.17 (range, 0.11 to 0.26) L/kg and 0.13 (range, 0.08 to 0.27) L/kg, the systemic clearance values were 0.32 (range, 0.18 to 0.56) mL/kg/hour and 0.26 (range, 0.15 to 0.65) mL/kg/hour, and the terminal half-life values were 20.8 (12 to 38) days and 20.6 (6 to 43) days in hematopoietic stem-cell transplant recipients aged 6 years and older with matched (8 of 8 HLA matched) and 1 allele-mismatched (7 of 8 HLA matched) unrelated donors, respectively.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
Intravenous Route
Comparable pharmacokinetic parameters of abatacept were noted among adult patients with rheumatoid arthritis (RA) and healthy patients. Among patients with RA, proportional increases of Cmax and AUC over the dose range of 2 to 10 mg/kg were noted after multiple intravenous infusions. At the 10 mg/kg dose level, the abatacept serum concentration appeared to reach a steady-state by day 60 with a mean trough (Cmin) concentration of 24 mcg/mL (range, 1 to 66 micrograms (mcg)/mL). No systemic accumulation of abatacept occurred upon continued repeated treatment with 10 mg/kg at monthly intervals. In a dose-ranging study involving adult psoriatic arthritis patients, steady-state was reached by day 57 and a geometric mean Cmin of 24.3 mcg/mL on day 169.
On post-transplant day 63, the mean Cmin levels after 4 doses of abatacept 10 mg/kg IV for the prevention of acute GVHD were 22.5 mcg/mL (coefficient of variation (CV), 243.9%) and 31.1 mcg/mL (CV, 114.4 %) in patients aged 6 years and older with matched (8 of 8 HLA matched) and 1 allele-mismatched (7 of 8 HLA matched) unrelated donors, respectively. After the first abatacept 10 mg/kg IV infusion dose, the mean Cmax levels were 172 (range, 107 to 254) mcg/mL and 221 (range, 163 to 292) mcg/mL in patients with matched and 1 allele-mismatched unrelated donors, respectively.
Subcutaneous Route
After subcutaneous administration, the bioavailability of abatacept is 79%. Abatacept exhibited linear pharmacokinetic parameters. The mean Cmax at steady state observed after 85 days of treatment was 48.1 mcg/mL (range, 9.8 to 132.4 mcg/mL). The mean Cmin at steady state was 32.5 mcg/mL (range, 6.6 to 113.8 mcg/mL). A mean trough concentration of 12.6 mcg/mL was achieved after 2 weeks of subcutaneous dosing without an intravenous load. In adult psoriatic arthritis patients, steady-state was reached by day 57 and a geometric mean Cmin of 25.6 mcg/mL on day 169 following weekly subcutaneous administration of abatacept 125 mg.