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Indications and Usage

Adult Rheumatoid Arthritis (RA): ORENCIA® (abatacept) is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA. ORENCIA may be used as monotherapy or concomitantly with disease-modifying, anti-rheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.

Important Limitations of Use: ORENCIA should not be administered concomitantly with TNF antagonists, and is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

Juvenile Idiopathic Arthritis (JIA): ORENCIA® (abatacept) is indicated for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular JIA. ORENCIA may be used as monotherapy or concomitantly with methotrexate (MTX).

Important Limitations of Use: ORENCIA should not be administered concomitantly with TNF antagonists, and is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

Adult Psoriatic Arthritis (PsA): ORENCIA® (abatacept) is indicated for the treatment of adult patients with active PsA.

Important Limitations of Use: ORENCIA should not be administered concomitantly with TNF antagonists, and is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

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Indications and Usage

Juvenile Idiopathic Arthritis (JIA): ORENCIA® (abatacept) is indicated for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular JIA. ORENCIA may be used as monotherapy or concomitantly with methotrexate (MTX).

Important Limitations of Use: ORENCIA should not be administered concomitantly with TNF antagonists, and is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

The AMPLE anti-CCP+ data are from a post-hoc analysis
of the AMPLE head-to-head noninferiority trial.

  • AMPLE 2-YEAR
    OVERVIEW
  • STUDY
    DESIGN
  • DISEASE
    ACTIVITY
  • PHYSICAL
    FUNCTION

ORENCIA results were comparable to adalimumab across multiple endpoints in biologic-naïve, predominantly seropositive RA patients

The AMPLE 2-Year Study is a 2-year, multinational, prospective, randomized, head-to-head noninferiority trial of adult MTX-IR patients.1,2

At baseline in the AMPLE 2-year trial, 75.5% of ORENCIA SC + MTX patients and 77.4% of adalimumab SC + MTX patients were RF+; 45% of ORENCIA SC + MTX patients and 47% of adalimumab SC + MTX patients were anti-CCP+.1-3

Anti-CCP, anti-cyclic citrullinated peptide; MTX-IR, inadequate responders to methotrexate; RF, rheumatoid factor.

Limitations of the study1

Double-blinding for the study drugs was not feasible due to the difficulty masking the adalimumab administration. Patients were not blinded with regard to study drug. To mitigate this limitation, the study used clinical assessors and radiographic readers, who were blinded with regard to each patient's treatment.

ACR Results1,2

Primary endpoint: Noninferiority was achieved as measured by ACR 20 at 1 year2

  • ORENCIA SC + MTX 64.8% (95% CI, 59.5% to 70.0%)
  • adalimumab SC + MTX 63.4% (95% CI, 58.2% to 68.6%)

Secondary Endpoints1

At 2 years
ORENCIA SC + MTX
adalimumab SC + MTX
Achieved DAS28-CRP <2.6 50.6% 53.3%
Radiographic nonprogression—
no change in TSS from baseline*
84.8% 83.8%
HAQ-DI improvement (≥0.3) 54.1% 48.8%

*Nonprogression was assessed using the modified Sharp/van der Heijde scoring system and was defined as ≤ the smallest detectable change.

2-Year Cumulative Safety Results in AMPLE1,2

  ORENCIA (n=318) adalimumab (n=328)
Serious adverse events (SAEs) 13.8% 16.5%
Related SAEs 3.5% 6.1%
Discontinuations due to SAEs 1.6% 4.9%
Infections and infestations 3.8% 5.8%
Adverse events (AEs) 92.8% 91.5%
Related AEs 41.5% 50.0%
Discontinuations due to AEs 3.8% 9.5%
Overall infections 76.1% 71.3%
Malignancies 2.2% 2.1%
Autoimmune events 3.8% 1.8%
Local injection site reactions 4.1% 10.4%
Deaths 0.3% 0.3%

Most common local injection site reactions reported were hematoma, pruritus, erythema, rash, hemorrhage, pain, and reaction.

There was one death in each of these arms; patients each experienced a cardiovascular event.

Some of the observed safety rates for ORENCIA and adalimumab in AMPLE may differ from those previously reported; please refer to the Full Prescribing Information for each product.

AMPLE Anti-CCP+ Data

A post-hoc exploratory analysis of 2-year results from AMPLE divided patients into quartiles based on their anti-CCP+ titers.1*

AU/mL, arbitrary units per milliliter.

*Anti-CCP status was defined by second-generation anti-CCP assay.

Recruitment for the AMPLE 2-Year Study was done by anti-CCP status chart review. For the post-hoc analysis, all available serum samples were analyzed for anti-CCP status. The percentage of anti-CCP patients will vary between 2-year study and post-hoc analysis.1

  • No consistent differences in baseline characteristics were identified across anti-CCP+ quartiles or treatment groups1
  • The number of patients per treatment group was similar in each anti-CCP+ quartile1

LIMITATIONS OF THE STUDY1

  • Baseline serum samples were not available for all patients in AMPLE
  • There were some differences in baseline characteristics across treatment groups but they were not consistent across quartiles
  • Patients were not stratified by anti-CCP titers at randomization
  • Lack of patient blinding in AMPLE may have influenced the patient-reported outcome measures
  • There is no standard, universally accepted ACPA assay; therefore, findings may have differed with an alternative assay

This post-hoc analysis was not powered to make a comparison between treatment arms.

Baseline Characteristics1

AMPLE Anti-CCP+ Data

Improvements in DAS28-CRP for ORENCIA were seen across all anti-CCP+ patients with the greatest improvements in patients with the highest titers1

Adjusted mean change from baseline in DAS28-CRP

This post-hoc analysis was not powered to make a comparison between treatment arms.

Anti-CCP-negative patients in both treatment groups did not achieve improvements as substantial as those for anti-CCP-positive patients.1

The adjusted mean treatment difference (AMTD) (95% CI) in DAS28-CRP for ORENCIA Q4 vs adalimumab Q4 was –0.45 (–1.00 to 0.10; P=0.112). At Day 729, the discontinuation rate was 20.8% for ORENCIA and 25.3% for adalimumab. Data were determined using analysis of covariance (ANCOVA); missing data points for any subject were imputed using last observation carried forward (LOCF).1-3

AMPLE Anti-CCP+ Data

Improvements in HAQ-DI for ORENCIA were seen
across all anti-CCP+ patients with the greatest
improvements in patients with the highest titers1

Adjusted mean change from baseline in HAQ-DI

This post-hoc analysis was not powered to make a comparison between treatment arms.

Anti-CCP-negative patients in both treatment groups did not achieve improvements as substantial as those for anti-CCP-positive patients.1

The adjusted mean treatment difference (AMTD) (95% CI) in HAQ-DI for ORENCIA Q4 vs adalimumab Q4 was –0.17 (–0.41 to 0.07; P=0.173). At Day 729, the discontinuation rate was 20.8% for ORENCIA and 25.3% for adalimumab. Data were determined using analysis of covariance (ANCOVA); missing data points for any subject were imputed using last observation carried forward (LOCF).1-3

More Important
Safety Information

Important Safety Information for ORENCIA® (abatacept)

Concomitant Use with TNF Antagonists: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63%) and serious infections (4.4%) compared to patients treated with only TNF antagonists (43% and 0.8%, respectively), without an important enhancement of efficacy.

Hypersensitivity: Anaphylaxis or anaphylactoid reactions can occur during or after an infusion and can be life-threatening. There were 2 cases (<0.1%; n=2688) of anaphylaxis or anaphylactoid reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in JIA clinical trials (0.5%; n=190). In postmarketing experience, a case of fatal anaphylaxis following the first infusion of ORENCIA was reported. Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

Infections: Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.

Immunizations: Live vaccines should not be given concurrently with ORENCIA or within 3 months of its discontinuation. The efficacy of vaccination in patients receiving ORENCIA is not known. ORENCIA may blunt the effectiveness of some immunizations. It is recommended that JIA patients be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating therapy with ORENCIA.

Use in Patients with Chronic Obstructive Pulmonary Disease (COPD): Adult COPD patients treated with ORENCIA developed adverse events more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. In adult RA studies, 97% of COPD patients treated with ORENCIA developed adverse reactions versus 88% treated with placebo and respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of adult RA patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with RA and COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.

Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.

Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972.

Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.

Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo).

Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in RA patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.

Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of JIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in JIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients.

Note concerning ORENCIA administration options: Intravenous dosing has not been studied in patients younger than 6 years of age. The safety and efficacy of ORENCIA ClickJectTM Autoinjector for subcutaneous injection has not been studied in patients under 18 years of age.

Please click here for Full Prescribing Information »

 More Important
Safety Information

Important Safety Information for ORENCIA® (abatacept)

Concomitant Use with TNF Antagonists: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63%) and serious infections (4.4%) compared to patients treated with only TNF antagonists (43% and 0.8%, respectively), without an important enhancement of efficacy.

Hypersensitivity: Anaphylaxis or anaphylactoid reactions can occur during or after an infusion and can be life-threatening. There were 2 cases (<0.1%; n=2688) of anaphylaxis or anaphylactoid reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in JIA clinical trials (0.5%; n=190). In postmarketing experience, a case of fatal anaphylaxis following the first infusion of ORENCIA was reported. Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

Infections: Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.

Immunizations: Live vaccines should not be given concurrently with ORENCIA or within 3 months of its discontinuation. The efficacy of vaccination in patients receiving ORENCIA is not known. ORENCIA may blunt the effectiveness of some immunizations. It is recommended that JIA patients be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating therapy with ORENCIA.

Use in Patients with Chronic Obstructive Pulmonary Disease (COPD): Adult COPD patients treated with ORENCIA developed adverse events more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. In adult RA studies, 97% of COPD patients treated with ORENCIA developed adverse reactions versus 88% treated with placebo and respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of adult RA patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with RA and COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.

Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.

Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972.

Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.

Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo).

Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in RA patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.

Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of JIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in JIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients.

Note concerning ORENCIA administration options: Intravenous dosing has not been studied in patients younger than 6 years of age. The safety and efficacy of ORENCIA ClickJectTM Autoinjector for subcutaneous injection has not been studied in patients under 18 years of age.

Please see Full Prescribing Information »

References: 1. Schiff M, Weinblatt ME, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014;73(1):86-94. 2. Weinblatt ME, Schiff M, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013;65(1):28-38. 3. Data on File. ABAT 142. Princeton, NJ: Bristol-Myers Squibb.