For questions about BMS medicines during this time, please call 1-800-721-8909.

Overview of Registrational Trial in MTX-naïve* Patients2

The AGREE Registrational Trial was a 12-month, placebo-controlled, double-blind, Phase IIIb trial. Adult patients
were randomized to ORENCIA IV + MTX (n=256) or
placebo + MTX (n=253). 89% of patients were anti-CCP+
while 96.5% were RF+ in the trial
.

AGREE: Study design and co-primary endpoints

*Or prior exposure to MTX ≤10 mg/week for ≤3 weeks with none administered for 3 months prior to enrollment.

Overview of Head-to-Head Noninferiority Trial vs adalimumab

The AMPLE 2-Year Trial was a randomized, Phase IIIb,
head-to-head noninferiority trial of adult MTX-IR patients, and is not contained within the Full Prescribing Information.3 It is a supportive trial to AGREE, which was studied in MTX-naïve patients and had a different comparator. Patients were randomized to ORENCIA SC + MTX (n=318) or adalimumab SC + MTX (n=328).3 45% and 47% of patients were anti-CCP+, while 75.5% and 77.4% of patients were RF+ in the trial, respectively.3,4

AMPLE 2-year: Study design and primary endpoints

Exploratory Biomarker-
Driven Study

In biologic-naïve, MTX-IR patients with moderate to severe RA

Results in Dual-Seropositive Patients from an Exploratory Biomarker-Driven Study

Early AMPLE was an exploratory, single-blinded, Phase IV study (N=80) of ORENCIA SC + MTX and adalimumab SC + MTX in which patients were anti-CCP+ (>3x upper limit of normal), RF+, biologic-naïve, and had moderate to severe RA for ≤12 months.1 Patients were also required to have ≥3.2 DAS28-CRP with ≥3 tender and 3 swollen joints, to meet ACR/EULAR 2010 criteria for RA, and to have used MTX for ≥12 weeks (stable dose ≥4 weeks prior to randomization).1

This is an exploratory study with
only exploratory objectives.
No formal sample size and power
calculation were provided.5

48% of dual-seropositive patients achieved
ACR 70 with ORENCIA SC + MTX1

70% achieved ACR 50 and
83% achieved ACR 20

ACR Response Rates at
6 Months (95% CI)*†

Exploratory Study Results Exploratory Study Results

48% of dual-seropositive patients achieved
DAS28-CRP <2.6 with ORENCIA SC + MTX1

DAS28-CRP <2.6 Response Rates
at 6 Months (95% CI)*†

Exploratory Study Results Exploratory Study Results

Safety was evaluated descriptively throughout the study and up to 8 weeks after the last study drug dose.
No new safety signals were identified during the short-term treatment period.1

Please see Pooled Safety Results below for ORENCIA IV across 5 clinical trials

Both groups received maximum tolerated (15-25 mg) stable doses of oral MTX weekly. Patients could discontinue after the
single-blinded (short-term treatment) period and continue to follow-up.

Key Limitations

  • Clinical assessors, but not patients, were blinded to the study drug. Double blinding was not feasible due to logistical barriers with masking adalimumab
  • Small sample size
  • Exploratory analyses; statistical significance of differences in response rates could not be assessed
  • Larger clinical studies are warranted to confirm the findings from this study

*With 40 subjects per treatment arm, the half-width of the 95% confidence interval for differences in proportion ranges from 17% to 21%.5
As-treated analysis population; missing values were imputed as nonresponders.

ACR, American College of Rheumatology; CRP, C-reactive protein; DAS28, Disease Activity Score–28 joints; EULAR, European League Against Rheumatism; MTX-IR, inadequate responders to methotrexate.

Selected Important
Safety Information

Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs 43%) and serious infections (4.4% vs 0.8%) compared to patients treated with only TNF antagonists, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.

The Important Safety Information is derived from the Clinical Trial Safety Data contained within the Full Prescribing Information.

Patients were anti-CCP+ and RF+, biologic-naïve, and had moderate to severe RA for
≤12 months. Patients were randomized 1:1 to ORENCIA SC (125 mg weekly) + MTX (n=40) or adalimumab SC (40 mg biweekly) + MTX (n=40) for 6 months.1 Patients receiving adalimumab switched to ORENCIA (in an open-label period) following a 6-week washout period.1

*Clinical assessors were blinded to the study drug. Double blinding was not feasible because of the logistic barriers to masking adalimumab. Both groups received maximum tolerated (15-25 mg) stable doses of oral MTX weekly. Patients could discontinue after the single-blinded (short-term treatment) period and continue to follow-up.

This is an exploratory study with
only exploratory objectives.
No formal sample size and power
calculation were provided.5

Baseline Characteristics1

Upon screening all patients were both
anti-CCP+ and RF+1*

As-treated group ORENCIA SC + MTX
n=40
adalimumab SC + MTX
n=40
Age, years 47.2 (12.2) 44.7 (16.3)
Female, n (%) 29 (73) 31 (78)
Anti-CCP2, U/mL 991.8 (1104.8) 1043.1 (1643.3)
RF positive, n (%) 39 (97.5) 39 (97.5)
DAS28-CRP 5.2 (1.1) 5.2 (1.2)
Disease duration, months 5.4 (2.4) 5.5 (2.9)
Tender joint count–
28 joints
11.5 (7.9) 12.9 (6.8)
Swollen joint count–
28 joints
10.0 (6.8) 10.1 (5.6)
HAQ-DI 1.3 (0.8) 1.4 (0.8)
CRP, mg/L 12.7 (17.3) 14.0 (30.7)

Data are mean (SD) unless otherwise indicated. Baseline is Day 1 of the study.

*One adalimumab-treated patient was positive for anti-CCP2 at screening but negative at baseline. Estimates of adjusted mean change were from a repeated-measures mixed model that included baseline value, treatment group, time, and time-by-treatment group interaction.

Key Inclusion Criteria1,6

  • Symptoms of RA (≤12 months prior to enrollment)
  • Anti-CCP positive >3X upper limit of normal
    (>30 U/mL)
  • RF positive (>14 IU/mL)
  • DAS28-CRP ≥3.2 with ≥3 tender and 3 swollen joints
  • Meets ACR/EULAR 2010 criteria for RA
  • MTX use ≥12 weeks (stable dose
    ≥4 weeks prior to randomization)

Key Exclusion Criteria1

  • History of other autoimmune diseases
  • Prior use of conventional DMARDs other than MTX
  • Prior use of biologic and targeted DMARDs
  • Chronic or recent acute serious infection

Select Efficacy Analyses1

Clinical efficacy at 6 months included:

  • ACR 20/50/70 responders
  • DAS28-CRP <2.6 response rates

Selected Important
Safety Information

Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). In postmarketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

  • In moderate to severe RA
    Identify dual-seropositive (anti-CCP+ and RF+) patients
  • Choose ORENCIA
  • Archery target with dual-seropositive (anti-CCP+ and RF+) symbol
Archery target with dual-seropositive (anti-CCP+ and RF+) symbol

In moderate to severe RA

  • Identify
    dual-seropositive
    (anti-CCP+ and RF+)
    patients
  • Choose ORENCIA

Head-to-Head
Noninferiority Trial

In a broad population of MTX-IR patients
with moderate to severe RA

Results from a Head-to-Head Noninferiority Trial vs adalimumab

AMPLE was a 2-year Phase IIIb, head-to-head noninferiority trial of adult MTX-IR patients, and is not contained within the Full Prescribing Information.3 It is a supportive trial to the AGREE Registrational Trial, which was studied in MTX-naïve patients and had a different comparator. For more information on AGREE, please see below and the Full Prescribing Information.

Patients were randomized to ORENCIA SC + MTX (n=318) or adalimumab SC + MTX (n=328).3 45% and 47% of patients were anti-CCP+, while 75.5% and 77.4% of patients were RF+ in the trial, respectively.3,4

Patients were required to have moderate to severe RA for ≤5 years, be MTX-IR and biologic-naïve, and have ≥3.2 DAS28-CRP and a history of ≥1 of the following: seropositivity for anti-CCP or RF, or an elevated ESR or CRP level.7

Key limitations of the trial3

Double blinding was not feasible due to difficulty in masking administration of adalimumab.

  • Patients were not blinded to study drug
  • However, clinical assessors and radiographic readers were blinded to mitigate this limitation

Patients achieved comparable efficacy with ORENCIA SC + MTX vs adalimumab SC + MTX—ACR rates were sustained from Year 1 to Year 23,7

Head-to-head noninferiority trial results Head-to-head noninferiority trial results

Selected Endpoints: ORENCIA demonstrated similar response rates to adalimumab in DAS28-CRP <2.6

1 Year:
ORENCIA SC + MTX: 43.3% (37.4% to 49.1%)
adalimumab SC + MTX: 41.9% (36.0% to 47.9%)

2 Years:
ORENCIA SC + MTX: 50.6% (44.4% to 56.8%)
adalimumab SC + MTX: 53.3% (47.0% to 59.5%)

Summary of 2-year cumulative safety results in AMPLE

Cumulative rates at Year 2 in the ORENCIA SC + MTX (n=318) and adalimumab SC + MTX (n=328) groups, respectively

  • Serious adverse events (SAEs)—13.8% versus 16.5%
    • Discontinuations due to SAEs—1.6% versus 4.9%
    • Infections and infestations—3.8% versus 5.8%
  • Adverse events (AEs)—92.8% versus 91.5%
    • Discontinuations due to AEs—3.8% versus 9.5%
  • Overall infections—76.1% versus 71.3%
  • Malignancies—2.2% versus 2.1%
  • Autoimmune events—3.8% versus 1.8%
  • Local injection site reactions*—4.1% versus 10.4%
  • Deaths—0.3% versus 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.

Please see Pooled Safety Results below for ORENCIA IV across 5 clinical trials.

Selected Important
Safety Information

Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.

  • 646 patients were randomized to ORENCIA SC + MTX (n=318; 125 mg once per week) or adalimumab SC + MTX (n=328; 40 mg every other week)3
  • AMPLE was designed to show a 12% noninferiority margin4
  • 86.2% of patients using ORENCIA and 82% of those using adalimumab completed Year 1 of the study3
  • 79.2% of patients using ORENCIA and 74.7% of those using adalimumab completed the study at 2 years3

Inclusion Criteria4,7

  • ≥18 years of age with moderate to severe RA for ≤5 years
  • Inadequate response to MTX and biologic naïve
  • ≥3.2 DAS28-CRP and a history of ≥1 of the following:
    • Seropositivity for anti-CCP or RF
    • Elevated ESR or CRP level

Key Exclusion Criteria4

  • Previous treatment with an investigational or approved
    biologic RA therapy
  • History of active or chronic hepatitis B
  • Subjects with any other rheumatic disease or
    with active vasculitis of a major organ

Primary Endpoint3,7

  • Noninferiority of ORENCIA SC vs adalimumab SC, assessed by ACR 20 at 1 year

Selected Secondary Endpoints3,7

  • ACR (50, 70) scores through 2 years
  • Proportion of patients achieving DAS28-CRP <2.6 through 2 years
  • Radiographic outcomes at Year 1 and Year 2 as measured by change in total modified Sharp score
  • Proportion of patients achieving a ≥0.3 improvement from baseline in HAQ-DI through 2 years

Other Efficacy Analyses

Descriptive statistics were provided by treatment for ACR 20, ACR 50, and ACR 70 at each scheduled visit and summarized using point estimates and 95% CIs. The proportion of subjects achieving each response was then plotted over time.

Key Baseline Characteristics3,4

ORENCIA SC + MTX
(n=318)
adalimumab SC + MTX
(n=318)
Mean disease duration, yr 1.9 1.7
Anti-CCP+* 45% 47%
RF+ 75.5% 77.4%
Mean DAS28-CRP 5.5 5.5
Joint Erosion 93% 96%

*Anti-CCP status was reported by patient’s medical history for 488 of the 646 patients.4
Seropositive RF antibodies as reported by patient’s medical history.3
Radiographic evidence of joint erosion.3

Selected Important
Safety Information

Immunizations: Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations.

Secondary Endpoint: Change in TSS3,7*

Secondary endpoint responses Secondary endpoint responses

*Based on readings at Year 1, the percentage of radiographic nonprogressors was 87.8% for ORENCIA and 88.6% for adalimumab. Graph shown is based on 2-year readings.3,7

Most patients taking ORENCIA did not have radiographic progression based on change in TSS from baseline at
Years 1 and 2

At Year 1, 87.8% of ORENCIA SC + MTX patients demonstrated no change in TSS from baseline.

At Year 2, 84.8% of ORENCIA SC + MTX patients demonstrated no change in TSS from baseline.3,7

Nonprogression was assessed using the modified
Sharp/van der Heijde scoring system and was defined as
change in total Sharp score ≤ the smallest detectable change.3

*Based on readings at Year 1, the percentage of radiographic nonprogressors was 87.8% for ORENCIA and 88.6% for adalimumab. Graph shown is based on 2-year readings.3,7

Selected Important
Safety Information

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

Secondary Endpoint: HAQ-DI Response Rates
(≥0.3 improvement)3

Secondary endpoint responses

54.1% of patients taking ORENCIA SC + MTX achieved a HAQ-DI improvement of ≥0.3 at 2 years.3

HAQ-DI, Heath Assessment Questionnaire-Disability Index.

Selected Important
Safety Information

Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.

Registrational Trial in
Seropositive Patients

In a 1-year trial of MTX-naïve* patients
with moderate to severe RA

Results in Predominantly Dual-Seropositive Patients from a Registrational Trial2

The AGREE Registrational Trial was a 12-month, placebo-controlled, double-blind, Phase IIIb trial. Adult patients were randomized to ORENCIA IV + MTX (n=256) or placebo + MTX (n=253). 89% of patients were anti-CCP+ while 96.5% were RF+ in the study.

Adult patients were required to have early (≤2 years) and active RA, be MTX-naïve,* and ≥12 tender and ≥10 swollen joints,
CRP ≥0.45 mg/dL, RF and/or anti-CCP positivity, and radiographic evidence of bone erosion of the hands, wrists, and feet.

*Or prior exposure to MTX ≤10 mg/week for ≤3 weeks with none administered for 3 months prior to enrollment.

ORENCIA IV + MTX significantly improved
DAS28-CRP <2.6 response rates and
radiographic results at 1 year vs MTX alone2

CO-PRIMARY ENDPOINTS2,8
At 1 year
ORENCIA IV + MTX
n=256
Placebo + MTX
n=253
Achieved DAS28-CRP <2.6
(95% CI)
41%
(35.4% to 47.4%)
P<0.001
23%
(18.1% to 28.5%)
Radiographic progression
(mean change from
baseline TSS)
0.6
P=0.04
1.1
SELECTED ENDPOINTS2,8
At 1 year
ORENCIA IV + MTX
N=256
Placebo + MTX
N=253
HAQ-DI improvement (≥0.3)
(95% CI)
72%
(66.4% to 77.4%)
P=0.024
62%
(56.1% to 68.0%)
Achieved ACR 20
(95% CI)
76%
(71.0% to 81.4%)
P<0.001
62%
(56.1% to 68.0%)
Achieved ACR 50
(95% CI)
57%
(51.4% to 63.5%)
P<0.001
42%
(36.2% to 48.4%)
Achieved ACR 70
(95% CI)
43%
(36.5% to 48.6%)
P<0.001
27%
(21.8% to 32.8%)

Mean change in Genant-modified TSS at 1 year. Refers to observed data for patient population.

HAQ-DI, Health Assessment Questionnaire–Disability Index.

Summary of safety at 1-year in the AGREE trial

The AGREE trial was an active-controlled clinical trial in methotrexate-naive patients. The safety experience in these patients was consistent with the patients studied across
5 clinical trials for ORENCIA IV. Please refer to the Pooled Safety below and Full Prescribing Information.

Selected Important Safety Information

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.

509 adult patients with early moderate to severe RA (≤2 years) who were MTX-naïve* were randomly assigned to treatment groups: ORENCIA IV + MTX (n=256) and placebo + MTX (n=253). ORENCIA IV (~10 mg/kg based on patient weight) was administered on Days 1, 15, and 29, and every 4 weeks thereafter. MTX was initially dosed at 7.5 mg/week and subsequently increased to 15 mg at Week 4 and to 20 mg at Week 8. Dose reduction was permitted to a minimum of 15 mg/week due to toxicity or intolerability.2

Key Patient Characteristics2

  • Mean disease duration: 6.5 months
  • Anti-CCP+: 89% of patients
  • RF+: 96.5% of patients
  • Mean DAS28-CRP: 6.3
  • Joint erosion: 100% of patients

Inclusion Criteria2

  • Early (≤2 years) and active RA according to ACR criteria
  • ≥18 years of age
  • MTX-naïve or prior exposure of
    ≤10 mg/week for
    ≤3 weeks, with none administered for 3 months
  • ≥12 tender and ≥10 swollen joints, CRP ≥0.45 mg/dL, RF and/or anti-CCP seropositivity, and radiographic evidence of bone erosion of the hands, wrists, and feet

Co-primary Endpoints2

  • Proportion of patients achieving DAS28-CRP <2.6 at 12 months
  • Radiographic progression measured by Genant-modified TSS at 12 months

Selected Secondary Endpoints2

  • ACR 50 response at 12 months
  • HAQ-DI improvement (≥ 0.3) at 12 months

Selected Endpoints at 12 Months2,9

  • ACR 20/70 responses

*Or prior exposure to MTX ≤10 mg/week for ≤3 weeks with none administered for 3 months prior to enrollment.
Radiographic evidence of bone erosion of the hands, wrists, and feet.

Selected Important
Safety Information

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.

ORENCIA IV + MTX improved radiographic results at 1 year vs MTX alone2*

Co-primary Endpoint: Radiographic Progression*

radiographic results radiographic results

*Mean change in Genant-modified TSS at 1 year. Missing data for the as-observed patient population in Month 6 were imputed by linear extrapolation at 1 year.2

Selected Important
Safety Information

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.

ORENCIA IV + MTX improved symptom relief at 1 year vs MTX alone for
predominantly dual-seropositive patients2,8

Selected Endpoint: ACR 20/50/702,8

 ACR 20/50/70 response rates

ORENCIA IV + MTX significantly improved the ACR 20, 50, and 70 response rates at 1 year vs MTX alone2,8

Selected Important
Safety Information

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

Pooled Safety Results9

Based on treatment of 2944 patients (1955 patients treated with ORENCIA IV, 989 with placebo) across 5 double-blind, placebo-controlled studies of 6 months or 1 year (101-100, 101-101, AIM, ASSURE, ATTAIN). A subset of these patients received concomitant biologic DMARD therapy, such as a TNF antagonist (204 patients with ORENCIA, 134 with placebo). The concomitant use of ORENCIA with a TNF antagonist is not recommended.

Most serious adverse reactions9

The most serious adverse reactions associated with ORENCIA therapy were serious infections and malignancies. In patients taking ORENCIA IV (n=1955),* the rate of serious infections was 3.0% and the rate of malignancies was 1.3%. In patients taking placebo (n=989), the rate of serious infections was 1.9% and the rate of malignancies was 1.1%.

Adverse reactions most frequently resulting in clinical intervention9

The adverse reactions most frequently resulting in clinical intervention (interruption or discontinuation of ORENCIA) were due to infection. The most frequently reported infections resulting in dose interruption were upper respiratory tract infection (1%), bronchitis (0.7%), and herpes zoster (0.7%). The most frequent infections resulting in discontinuation were pneumonia (0.2%), localized infection (0.2%), and bronchitis (0.1%).

Most common adverse reactions9

Adverse reactions occurring in 3% or more of patients and at least 1% more frequently in patients treated with ORENCIA IV during placebo-controlled RA studies:

ORENCIA IV (n=1955)* Placebo (n=989)
Headache 18% 13%
Nasopharyngitis 12% 9%
Dizziness 9% 7%
Cough 8% 7%
Back pain 7% 6%
Hypertension 7% 4%
Dyspepsia 6% 4%
Urinary tract infection 6% 5%
Rash 4% 3%
Pain in extremity 3% 2%

*Includes 204 patients on concomitant biologic DMARDs (adalimumab, anakinra, etanercept, or infliximab).9
Includes 134 patients on concomitant biologic DMARDs (adalimumab, anakinra, etanercept, or infliximab).9

Infections9

In placebo-controlled trials, infections were reported in 54% of ORENCIA-treated patients and 48% of placebo-treated patients.

The most commonly reported infections (5%-13% of patients) were upper respiratory tract infection, nasopharyngitis, sinusitis, urinary tract infection, influenza, and bronchitis.

The safety experience of ORENCIA SC was consistent with that of ORENCIA IV.

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Important Safety Information
for ORENCIA® (abatacept)

Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs 43%) and serious infections (4.4% vs 0.8%) compared to patients treated with only TNF antagonists, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.

Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). In postmarketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. Caution should be exercised in patients with
a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.

Immunizations: Prior to initiating ORENCIA
in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA
or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of
some immunizations.

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

Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in
patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.

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 patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential
role of ORENCIA in the development of malignancies in humans is unknown.

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

Note concerning ORENCIA administration options: ORENCIA may be administered as an intravenous infusion only for patients 6 years of age and older. PJIA patients may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determines it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested.

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References: 1. Rigby W, Buckner J, Bridges SL, et al. The effect of
HLA-DRB1 risk alleles on the clinical efficacy of abatacept and adalimumab in seropositive biologic-naïve patients with early, moderate-to-severe RA: data from a head-to-head single blinded trial. Poster LB0008. Presented at EULAR Annual European Congress of Rheumatology, Madrid, Spain, June 12-15, 2019. 2. Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis. 2009;68(12):1870-1877. 3. 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. 4. Data on File. ABAT 143. Princeton, NJ: Bristol Myers Squibb. 5. Data on File. ABAT 166. Princeton, NJ: Bristol Myers Squibb. 6. Data on File. IM-101567 (lab values). Princeton, NJ: Bristol Myers Squibb. 7. 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. 8. Data on File. ABAT 032. Princeton, NJ: Bristol Myers Squibb. 9. ORENCIA [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.