Abatacept is a fully human recombinant fusion protein categorized as a costimulatory or second-signal blocker of T cell activation. It is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) or active psoriatic arthritis (PsA) and in pediatric patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis. Abatacept is also indicated 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. Concomitant use of abatacept with other immunosuppressives (e.g., biologic disease-modifying antirheumatic drugs [DMARDS] or Janus kinase [JAK] inhibitors) is not recommended. As with many biologic therapies, the effects of abatacept may increase the risk for serious infection. In adults with RA or PsA, abatacept improves clinical signs and symptoms and improves physical function; in adults with RA, abatacept inhibits the radiographic progression of structural joint damage. Like other non-TNF targeted treatments, abatacept is usually reserved for patients with RA or PsA who have contraindications, intolerance, or inadequate response to biologic agents such as the TNF inhibitors. The ideal combination of therapy for individual patients with inflammatory arthritis conditions such as RA and PsA is determined by treat to target strategies and severity of the disease.
Updates for coronavirus disease 2019 (COVID-19):
According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, abatacept may be used as an alternative to baricitinib or tocilizumab for the treatment of COVID-19 in hospitalized patients:
-on conventional oxygen who are exhibiting signs of systemic inflammation and rapidly increasing oxygen needs while receiving dexamethasone
-on high-flow oxygen or noninvasive ventilation
Abatacept must be given in combination with dexamethasone (with or without remdesivir), and is only recommended for use when baricitinib and tocilizumab are unavailable or cannot be administered. The drug is not recommended for use in patients requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO), as benefit in these patients has not been established.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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. Investigational doses for COVID-19 are administered over 30 minutes.
-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.
Of 1,955 rheumatoid arthritis patients who received abatacept infusions, 18% reported a headache and 9% reported dizziness. Headache was also reported in at least 5% of pediatric patients. Additionally, dizziness and headache may be associated with the infusion and are reported at a rate of 1 to 2%. Infusion-related adverse reactions develop within one hour of the start of the infusion. Most of these reactions were mild to moderate; less than 1% of patients discontinued abatacept because of an acute infusion-related event. The overall safety of subcutaneous abatacept is reported to be consistent with that of the infusion formulation.
Abatacept and increases the risk for serious infection. Serious infections, including sepsis and pneumonia, have been reported in patients receiving abatacept. 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. Infections occurred in 54% of intravenous (IV) abatacept-treated patients and in 48% of placebo-treated patients enrolled in rheumatoid arthritis studies. Serious infections, including pneumonia, cellulitis, urinary tract infection, bronchitis, diverticulitis, and acute pyelonephritis, were reported in 3% of patients during IV abatacept clinical trials vs. 1% of those receiving placebo. Upper respiratory tract infection, nasopharyngitis/pharyngitis, sinusitis, urinary tract infection, influenza, and bronchitis were the most common types of infections (5% to 13%), but rhinitis, herpes simplex, and pneumonia also occurred in less than 5% of patients. In rheumatoid arthritis studies (n = 1,955), nasopharyngitis was reported in 12% and urinary tract infection in 6% of IV abatacept patients. Approximately 10% of the studied patients were also taking anakinra or a TNF antagonist concomitantly; a higher rate of serious infections has been observed in adult RA patients treated with concurrent TNF antagonists and abatacept compared to those treated with abatacept alone. The use of anakinra, a TNF antagonist, or other biologic or targeted DMARD with abatacept is NOT advised due to the increased risk for serious infection and immunosuppression. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept. The most common infections resulting in dose interruption during RA clinical trials included upper respiratory tract infection (1%), bronchitis (0.7%), and herpes zoster (0.7%). The most common infections resulting in therapy discontinuation included pneumonia (0.2%), localized infection (0.2%), and bronchitis (0.1%). The safety profile of subcutaneous abatacept was found to be similar to IV abatacept in both RA and psoriatic arthritis trials. In pediatric patients with juvenile idiopathic arthritis (n = 190), infections were reported in 36% of IV abatacept patients with upper respiratory tract infections and nasopharyngitis reported as the most common infections; there was one case of varicella infection. In a comparative study, the overall safety of the subcutaneous formulation was consistent with that of the IV formulation. Grade 3 or 4 pneumonia occurred in 19% and 12% of patients (age range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial. Patients who develop a new infection while undergoing treatment should be monitored closely. Discontinue abatacept if a patient develops a serious infection.
Gastrointestinal (GI) adverse events with abatacept have been reported. Dyspepsia was noted in 6% of rheumatoid arthritis patients treated with abatacept infusion. Nausea was reported in 10% or more of adult patients enrolled in the IV abatacept rheumatoid arthritis studies. Nausea, diarrhea, and abdominal pain were reported in at least 5% of pediatric patients as well. Additionally, nausea may be associated with IV infusion-related adverse reactions and was reported in more than 0.1% to 1% or less of patients; these reactions usually develop within 1 hour of the start of the infusion. Most of these reactions were mild to moderate; less than 1% of patients discontinued abatacept because of an acute infusion-related event. Although the specific rates of these GI adverse events are not known for patients treated with subcutaneous abatacept, the overall safety of the subcutaneous formulation is reported to be similar to that of the infusion formulation.
Dermatologic and local injection site reactions may occur with abatacept use. An injection site reaction, including local hematoma, pruritus, and erythema, occurred in 2.6% of patients treated with subcutaneous abatacept vs. 2.5% of those treated with subcutaneous placebo or abatacept IV infusion; these were mild to moderate in severity. Local injection site reactions were reported in 4.4% of pediatric patients who received subcutaneous abatacept in an open-label study. Rash was reported in 4% of 1,955 rheumatoid arthritis patients treated with abatacept IV infusion. The incidence of rash has not been reported in patients treated with subcutaneous abatacept; however, it is reported that the safety profile of subcutaneous abatacept is similar to that of the infusion formulation. Rash, flushing, and urticaria have also been reported as IV infusion-related abatacept reactions and were reported in more than 0.1% to 1% or less of patients; these adverse reactions usually develop within 1 hour of the start of the infusion. Most of the infusion reactions were mild to moderate; less than 1% of patients discontinued IV abatacept because of an acute infusion-related event. Postmarketing reports of systemic reactions (e.g., pruritus) have occurred following the use of subcutaneous abatacept. New or worsening psoriasis has also been reported with postmarketing use of abatacept.
Cough was reported in 8% of 1,955 rheumatoid arthritis patients treated with abatacept IV infusion. Cough was also reported in at least 5% of pediatric patients. Cough, dyspnea, and wheezing may also be associated with abatacept IV infusion and were reported in more than 0.1% to 1% or less of patients; these infusion-related adverse reactions usually develop within 1 hour of the start of the infusion. Most of the infusion reactions were mild to moderate; less than 1% of patients discontinued IV abatacept because of an acute infusion-related event. Patients with chronic obstructive pulmonary disease (COPD) have been noted to be more at risk for respiratory-related side effects due to abatacept. Respiratory disorders were reported more frequently in COPD patients treated with abatacept at 43% (n = 37) compared to placebo at 24% (n = 17) including COPD exacerbation, cough, rhonchi, and dyspnea. Although the specific rates of these adverse events are not known for patients treated with subcutaneous abatacept, the overall safety profile of the subcutaneous formulation is reported to be similar to that of the IV infusion formulation. Systemic injection reactions, including dyspnea, have been reported with postmarketing use of subcutaneous abatacept.
Hypertension was reported in 7% of 1,955 rheumatoid arthritis patients treated with abatacept IV infusion. Additionally, grade 3 or 4 hypertension occurred in 49% and 43% of patients (age range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial. Hypertension, hypotension, and increased blood pressure may be associated with the infusion. Hypertension occurred in 1% to 2% of these patients, while hypotension and increased blood pressure were reported in more than 0.1% to 1% or less of patients. The infusion-related adverse reactions usually develop within 1 hour of the start of the infusion and most of these reactions were mild to moderate; less than 1% of patients discontinued IV abatacept because of an acute infusion-related event. Although the specific rates of these adverse events are not known for patients treated with subcutaneous abatacept, the overall safety profile of the subcutaneous formulation is reported to be similar to the IV infusion formulation.
Anaphylaxis or anaphylactoid reactions have been reported in less than 0.1% of patients during abatacept IV infusion clinical trials. Anaphylactic shock or anaphylactoid reactions can be life-threatening. One case of fatal anaphylaxis following the first abatacept dose and life-threatening cases of angioedema have been reported with postmarketing use of abatacept and have been reported following the first dose as well as with subsequent doses. Angioedema may occur within hours of abatacept administration or have a delayed onset of days later. Appropriate medical support should be available for immediate use in the event of a serious hypersensitivity reaction. If an anaphylactic or serious allergic reaction occurs, immediately stop the medication and begin appropriate medical support measures; in these patients, the use of abatacept should be permanently discontinued. Patients using subcutaneous abatacept should seek immediate medical assistance and treatment. Acute infusion-related reactions may occur with abatacept IV infusion. Acute infusion-related adverse reactions occurring within 1 hour of the start of infusion were more common in abatacept-treated patients (9%) vs. placebo patients (6%) in rheumatoid arthritis trials. The most frequently reported (1% to 2%) infusion-related reactions include dizziness, headache, and hypertension. Additionally, hypotension, increased blood pressure, dyspnea, nausea, flushing, urticaria, cough, pruritus, rash, and wheezing may be associated with the IV abatacept infusion and were reported in more than 0.1% to 1% or less of patients. Most of these reactions were mild to moderate; less than 1% of patients discontinued abatacept because of an acute infusion-related event. Infusion-related events have been reported in pediatric patients at a frequency of 2% to 4% and were consistent with events reported in adult patients. Postmarketing reports of other systemic reactions (e.g., pruritus, throat tightness, dyspnea) have occurred following the use of subcutaneous abatacept.
Back pain (7%) and pain in the extremity (musculoskeletal pain, 3%) were reported during rheumatoid arthritis trials (n = 1,955) of abatacept infusion. One case of joint wear was reported in pediatric trials during the initial 4 months of treatment. Although the specific rates of these adverse events are not known for patients treated with subcutaneous abatacept, the overall safety profile of the subcutaneous formulation is reported to be similar to that of the infusion formulation.
Fever was reported in at least 5% of pediatric patients during juvenile idiopathic arthritis trials with abatacept IV infusion. Fever occurred in 28% (grade 3 or 4, 9%) and 19% (grade 3 or 4, 10%) of patients aged 6 years and older (range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial. Additionally, 1 case of ovarian cyst and 2 cases of disease flare were reported during the initial 4 months of IV treatment. Although the specific rates of these adverse events are not known for patients treated with subcutaneous abatacept, in comparative study the overall safety of the subcutaneous formulation was consistent with that of the IV infusion formulation.
Vasculitis, specifically cutaneous and leukocytoclastic vasculitis, has been associated with abatacept use during the postmarketing period. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Antibody formation against abatacept has been reported, but no correlation of antibody development to pharmacokinetics, clinical response, or adverse events was observed. In rheumatoid arthritis (RA) patients assessed for up to 2 years after repeated treatment with abatacept IV infusion, 34 of 1,993 (1.7%) developed binding antibodies to the entire abatacept molecule or to the CTLA-4 portion. Because trough concentrations can interfere with the assay, a subset analysis was performed and binding antibodies were noted in 9 of 154 (5.8%) patients who had not received abatacept infusion for at least 56 days. Six of the 9 patients were shown to possess neutralizing antibodies. In an adult RA study, the overall immunogenicity frequency to abatacept was 1.1% in subcutaneously-treated patients and 2.3% in IV-treated patients. The effect of discontinuing treatment, then restarting treatment, has also been studied. Patients were enrolled in the first 3-month treatment period and responders (n= 120) were randomized to either subcutaneous abatacept or placebo for the second 3-month period (withdrawal period). Patients from this period then received open-label abatacept treatment in the final 3-month period of the study (period 3). At the end of the withdrawal period, 0/38 (0%) patients who continued to receive subcutaneous abatacept developed anti-abatacept antibodies compared to 7/73 (10%) of patients who had the drug withdrawn during this period. Half of the patients who received subcutaneous placebo during the withdrawal period received a single IV infusion of abatacept at the start of period 3 and half received IV placebo. At the end of period 3, when all patients again received subcutaneous abatacept, the immunogenicity rates were 1/38 (3%) in the group who received subcutaneous abatacept throughout, and 2/73 (3%) in the group that had received placebo during the withdrawal period. Upon reinitiating therapy, there were no injection reactions and no differences in response to therapy in patients who were withdrawn from subcutaneous therapy for up to 3 months compared to those who remained on subcutaneous therapy (these results occurred in those who received or did not receive an intravenous loading dose). The safety observed in this study was consistent with that observed in the other studies. Among pediatric patients enrolled in an IV abatacept study, antibodies were detected in 41% of patients who withdrew therapy for up to 6 months during the double-blind period compared to 13% of patients who remained on therapy. Samples from 20 patients were tested for the presence of neutralizing antibodies and, of those, 8 (40%) were found to have neutralizing activity. The presence of antibodies was generally transient, and titers were low. The presence of antibodies was not associated with adverse events, changes in efficacy, or an effect on serum concentrations of abatacept. During the treatment period (day -1 to day 28 post-transplant), there was no documented antibody formation in 114 evaluable patients aged 6 years and older who were undergoing an unrelated allogeneic stem-cell transplant and received 4 doses of abatacept IV as acute GVHD prophylaxis. During the off-treatment period (days 29 to 180 post-transplant), 6 of 91 (6.6%) evaluable patients developed CTLA4 and possibly Ig antibodies; 1 of these patients had neutralizing antibodies.
Abatacept may be associated with the development of a new primary malignancy. There are insufficient data to determine if an association exists between the occurrence of malignancy and the dose or duration of exposure to abatacept. The overall frequencies of malignancies were similar between the 1,955 patients who received either intravenous abatacept (1.3%) or placebo (1.1%) for a median of 12 months in rheumatoid arthritis clinical trials. However, none of the placebo-treated patients developed lung cancer whereas 4 (0.2%) of the abatacept-treated patients did. Also, there were 8 cases of lung cancer (0.21 cases per 100 patient-years) and 4 cases of lymphoma (0.10 cases per 100 patient-years) in the cumulative intravenous abatacept trials (placebo-controlled and uncontrolled, open-label trials). The rate of lymphoma was approximately 3.5-fold higher than expected in an age- and gender-matched general population based on the Surveillance, Epidemiology, and End Results Database. Other cancers included skin, breast, bile duct, bladder, cervical, endometrial, melanoma, myelodysplastic syndrome, ovarian, prostate, renal, thyroid, and uterine cancers. Patients with rheumatoid arthritis, especially those with highly active disease, are at a higher risk for lymphoma development. Additionally, many patients had a long duration of chronic exposure to immunosuppressant therapies, a population at greater risk for the development of a new primary malignancy. Acute lymphocytic leukemia was reported in 1 (n = 190) pediatric patient treated for juvenile idiopathic arthritis. Cases of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) have been reported with postmarketing use of abatacept.
Post-transplant lymphoproliferative disorder (PTLD) associated with Epstein-Barr virus (EBV) infection (3.4%), EBV reactivation (less than 10%), and cytomegalovirus (CMV) invasive disease (7%) were reported in patients who were undergoing an unrelated allogeneic stem-cell transplant and received 4 doses of abatacept IV as prophylaxis for acute GVHD in a 2-cohort trial (n = 116). 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. In the 4 patients that developed EBV infection, the time to onset was 49 to 89 days post-transplant; however, 3 of 4 patients had discontinued acyclovir prophylaxis at day 30 post-transplant. In patients that developed a CMV infection, the median time to onset was 91 days and all occurred within 225 days post-transplant. Most CMV invasive infection involved the gastrointestinal tract. Grade 3 or 4 CMV reactivation/CMV infection occurred in 26% and 32% of patients (age range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial.
Hematologic adverse events including grade 3 or 4 anemia (56% and 69%) and decreased CD4 lymphocytes/lymphopenia (14% and 14%) occurred in patients (age range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial.
Grade 3 or 4 epistaxis occurred in 12% and 16% of patients (age range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial.
Nephrotoxicity, specifically acute kidney injury, occurred in 9% (grade 3 or 4, 7%) and 15% (all grade 3 or 4) of patients (age range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial.
Grade 3 or 4 hypermagnesemia occurred in 5% and 18% of patients (age range, 6 to 76 years) who received 4 doses of abatacept IV as acute GVHD prophylaxis and underwent an allogeneic stem-cell transplant from a 1 allele-mismatched (n = 43) and matched (n = 73) unrelated donor, respectively, in a 2-cohort trial.
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.
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.
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.
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.
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.
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.
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. For COVID-19, the National Institutes of Health (NIH) states that the decision to administer abatacept to a pregnant patient must be shared between the patient and their healthcare providers, and that potential maternal benefit and fetal risks must be considered. 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.
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. For COVID-19, the National Institutes of Health (NIH) states that abatacept should be offered to lactating patients who qualify for therapy, and that breast-feeding may be considered during treatment with abatacept.
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.
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.
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.
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 to 17 years weighing 50 kg or more: 125 mg subcutaneously once weekly.
Children and Adolescents 2 to 17 years weighing 25 to 49 kg: 87.5 mg subcutaneously once weekly.
Children and Adolescents 2 to 17 years weighing 10 to 24 kg: 50 mg subcutaneously once weekly.
Intravenous dosage:
Children and Adolescents 6 to 17 years weighing more than 100 kg: 1,000 mg IV every 2 weeks for 3 doses. Starting at week 8, give 1,000 mg IV every 4 weeks.
Children and Adolescents 6 to 17 years weighing 75 to 100 kg: 750 mg IV every 2 weeks for 3 doses. Starting at week 8, give 750 mg IV every 4 weeks.
Children and Adolescents 6 to 17 years weighing less than 75 kg: 10 mg/kg/dose IV every 2 weeks for 3 doses. Starting at week 8, give 10 mg/kg/dose IV every 4 weeks.
For the treatment active psoriatic arthritis:
Intravenous dosage:
Adults weighing more than 100 kg: 1,000 mg IV every 2 weeks for 3 doses. Starting at week 8, give 1,000 mg IV 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 every 2 weeks for 3 doses. Starting at week 8, give 750 mg IV 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 every 2 weeks for 3 doses. Starting at week 8, give 500 mg IV 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).
Children and Adolescents 2 to 17 years weighing 50 kg or more: 125 mg subcutaneously once weekly. Abatacept may be administered with or without methotrexate.
Children and Adolescents 2 to 17 years weighing 25 to 49 kg: 87.5 mg subcutaneously once weekly. Abatacept may be administered with or without methotrexate.
Children and Adolescents 2 to 17 years weighing 10 to 24 kg: 50 mg subcutaneously once weekly. Abatacept may be administered with or without methotrexate.
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.
INVESTIGATIONAL USE: For the treatment of coronavirus disease 2019 (COVID-19)*, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection*, in certain hospitalized patients who are receiving systemic corticosteroids and require supplemental oxygen, including high-flow oxygen or noninvasive mechanical ventilation:
Intravenous dosage:
Adults: 10 mg/kg using actual body weight (up to a maximum dose of 1,000 mg) administered as a single IV infusion over 30 minutes is recommended by the National Institutes of Health (NIH) COVID-19 treatment guidelines for use in combination with dexamethasone (with or without remdesivir) to treat hospitalized adults requiring supplemental oxygen, IF the patient is exhibiting signs of systemic inflammation and rapidly increasing oxygen needs while on dexamethasone OR the patient requires high-flow oxygen or noninvasive mechanical ventilation. Abatacept is to be used as an alternative to baricitinib and tocilizumab when these medications are unavailable or cannot be administered.
For the treatment of temporal arteritis*:
Intravenous dosage:
Adults weighing more than 100 kg: 1,000 mg IV on days 1, 15, 29, and week 8, initially. If remission is achieved at week 12, then 1,000 mg IV every 4 weeks. Use in combination with a tapering dose of glucocorticoids. Guidelines suggest that abatacept with glucocorticoids may be considered if tocilizumab or methotrexate with glucocorticoids or glucocorticoid monotherapy are not effective.
Adults weighing 60 to 100 kg: 750 mg IV on days 1, 15, 29, and week 8, initially. If remission is achieved at week 12, then 750 mg IV every 4 weeks. Use in combination with a tapering dose of glucocorticoids. Guidelines suggest that abatacept with glucocorticoids may be considered if tocilizumab or methotrexate with glucocorticoids or glucocorticoid monotherapy are not effective.
Adults weighing less than 60 kg: 500 mg IV on days 1, 15, 29, and week 8, initially. If remission is achieved at week 12, then 500 mg IV every 4 weeks. Use in combination with a tapering dose of glucocorticoids. Guidelines suggest that abatacept with glucocorticoids may be considered if tocilizumab or methotrexate with glucocorticoids or glucocorticoid monotherapy are not effective.
Maximum Dosage Limits:
-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
COVID-19
Investigational doses of 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
COVID-19
Investigational doses of 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 to 49 kg: 87.5 mg per week subcutaneously
Weight 10 to 24 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
Psoriatic Arthritis (PsA )
Weight 50 kg or more: 125 mg per week subcutaneously
Weight 25 to 49 kg: 87.5 mg per week subcutaneously
Weight 10 to 24 kg: 50 mg per week subcutaneously
aGVHD prophylaxis
10 mg/kg (Max: 1,000 mg) IV.
-Children
Polyarticular juvenile idiopathic arthritis (pJIA)
2 to 12 years:
Weight 50 kg or more: 125 mg per week subcutaneously
Weight 25 to 49 kg: 87.5 mg per week subcutaneously
Weight 10 to 24 kg: 50 mg per week subcutaneously
Safety and efficacy of subcutaneous use have not been established in children younger than 2 years of age.
6 to 12 years:
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 younger than 6 years of age.
Psoriatic Arthritis (PsA )
2 to 12 years:
Weight 50 kg or more: 125 mg per week subcutaneously
Weight 25 to 49 kg: 87.5 mg per week subcutaneously
Weight 10 to 24 kg: 50 mg per week subcutaneously
Safety and efficacy of subcutaneous use have not been established in children younger than 2 years of age.
aGVHD prophylaxis
6 to 12 years: 10 mg/kg (Max: 1,000 mg) IV.
2 to 5 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 younger than 2 years of age.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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.
Albuterol; Budesonide: (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.
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; 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.
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.
Azelastine; Fluticasone: (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.
Bacillus Calmette-Guerin Vaccine, BCG: (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.
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.
Beclomethasone: (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.
Betamethasone: (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.
Budesonide: (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.
Budesonide; Formoterol: (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.
Budesonide; Glycopyrrolate; Formoterol: (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.
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.
Chikungunya Vaccine, Live: (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.
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.
Ciclesonide: (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.
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.
Cortisone: (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.
Deflazacort: (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.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dexamethasone: (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.
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.
Fludrocortisone: (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.
Flunisolide: (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.
Fluticasone: (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.
Fluticasone; Salmeterol: (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.
Fluticasone; Umeclidinium; Vilanterol: (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.
Fluticasone; Vilanterol: (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.
Formoterol; Mometasone: (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.
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.
Hydrocortisone: (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.
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.
Intranasal Influenza Vaccine: (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.
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.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (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.
Measles/Mumps/Rubella Vaccines, MMR: (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.
Methylprednisolone: (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.
Mometasone: (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.
Olopatadine; Mometasone: (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.
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.
Prednisolone: (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.
Prednisone: (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.
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.
Rotavirus Vaccine: (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.
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.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (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.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (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.
Smallpox Vaccine, Vaccinia Vaccine: (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.
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.
Triamcinolone: (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.
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.
Typhoid Vaccine: (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.
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.
Varicella-Zoster Virus Vaccine, Live: (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.
Yellow Fever Vaccine, Live: (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.
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).
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
-Route-Specific Pharmacokinetics
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.
-Special Populations
Hepatic Impairment
No formal studies were conducted to examine the effects of hepatic impairment on the pharmacokinetic parameters of abatacept.
Renal Impairment
No formal studies were conducted to examine the effects of renal impairment on the pharmacokinetic parameters of abatacept.
Pediatrics
In pediatric patients aged 6 to 17 years with polyarticular juvenile idiopathic arthritis (pJIA) who received intravenous abatacept, the mean steady-state serum peak concentration of abatacept was 217 (range, 57 to 700) mcg/mL. The mean steady-state serum trough concentration of abatacept was 11.9 (range, 0.15 to 44.6) mcg/mL. The estimated mean clearance of abatacept among patients with juvenile idiopathic arthritis was 0.4 (range, 0.2 to 1.12) mL/kg/hour.
In pediatric patients aged 2 to 17 years with pJIA who received body-weight-tiered subcutaneous abatacept once weekly, steady-state was reached at day 85. Mean trough concentrations at day 113 for patients weighing 10 kg to less than 25 kg, 25 kg to less than 50 kg, and more than 50 kg were 44.4 mcg/mL, 46.6 mcg/mL, and 38.5 mcg/mL, respectively. Similar to adult patients, the clearance of abatacept was also found to increase with baseline body weight among patients aged 6 to 17 years. After accounting for the effect of body weight, the clearance of abatacept was not related to age and gender.
Based on population pharmacokinetic modeling and simulation data, the AUC values following the first and last dose of abatacept in pediatric patients aged 2 to less than 6 years who received abatacept 15 mg/kg as a 60-minute IV infusion on day -1 followed by 12 mg/kg IV on days 5, 14, and 28 for acute GVHD prophylaxis are comparable with AUC values in patients aged 6 to less than 17 years and adults patients who received abatacept 10 mg/kg as a 60-minute IV infusion on days -1, 5, 14, and 28.
Geriatric
Age was not shown to have an effect on the pharmacokinetics of abatacept.
Gender Differences
Gender, after accounting for the effect of body weight, was not shown to have an effect on the pharmacokinetics of abatacept.
Obesity
A trend toward higher clearance of abatacept with increasing body weight was noted; clearance of abatacept also increased with baseline body weight among pediatric patients 6 to 17 years of age.
Other
HLA-matched status in hematopoietic stem-cell transplant (HSCT) recipients
In HSCT recipients, patients with 1 allele-mismatched (7 of 8 HLA matched) unrelated donors had 29% lower clearance of abatacept compared with patients with matched (8 of 8 HLA matched) unrelated donors.