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In moderate to severe rheumatoid arthritis (RA)

See ORENCIA in a different light

Choose a study to explore on this page

AMPLE 2-Year

NORD-STAR

AGREE

ATTAIN

ACTION

AMPLE 2-Year

NORD-STAR

AGREE

ATTAIN

ACTION

Overview of Registrational Trial in MTX-naïve* Patients1

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).

AGREE: Study design and co-primary endpoints

IV, intravenous; MTX, methotrexate.

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

AMPLE 2-Year

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

ORENCIA was studied
head-to-head in a noninferiority trial vs adalimumab2

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. 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).1,2

Comparable efficacy vs adalimumab2

Line chart of DAS28-CRP mean change from baseline vs adalimumab at Year 2.

ACR, American College of Rheumatology; CRP, C-reactive protein; DAS28, Disease Activity Score in 28 joints; MTX-IR, inadequate response to methotrexate; SC, subcutaneous.

Over half of patients had ≥1 comorbid condition3

Primary Endpoint2

Noninferiority measured by ACR 20 at 1 year

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

Selected Secondary Endpoint2

Remission rates* vs adalimumab (DAS28-CRP <2.6 at 2 years)

  • ORENCIA SC + MTX – 50.6% (44.0% to 56.8%
  • adalimumab SC + MTX – 53.3% (47.0% to 59.5%)

*Remission is defined as DAS28-CRP <2.6.4 Clinical remission does not mean drug-free remission or complete absence of disease activity.

Comparable efficacy vs adalimumab2

Line chart of DAS28-CRP mean change from baseline vs adalimumab at Year 2.

ACR, American College of Rheumatology; CRP, C-reactive protein; DAS28, Disease Activity Score in 28 joints; MTX-IR, inadequate response to methotrexate; SC, subcutaneous.

Baseline Characteristics3

Study reports did not always include detailed patient characteristic data for all individual patients. In patients for whom detailed characteristic data were available, 62% of patients in the ORENCIA group (n=310) had at least one comorbid condition, with the most frequent being high blood pressure (42%) and high cholesterol (26%).

In the adalimumab group, 315 patients had detailed patient characteristic data. At least one comorbid condition was identified in 55% of patients, with the most frequent being high blood pressure (38%) and high cholesterol (26%).

Study Design2

646 patients were randomized into the ORENCIA subcutaneous and methotrexate arm with 318 patients taking 125 milligrams per week or the adalimumab subcutaneous and methotrexate arm with 328 patients taking 40 milligrams bi-weekly. 646 patients were randomized into the ORENCIA subcutaneous and methotrexate arm with 318 patients taking 125 milligrams per week or the adalimumab subcutaneous and methotrexate arm with 328 patients taking 40 milligrams bi-weekly.

Primary Endpoint2

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

Selected Secondary Endpoint2

Proportion achieving remission* (DAS28-CRP <2.6)

  • 86.2% of patients using ORENCIA and 82% of those using adalimumab completed Year 1 of the study
  • 79.2% of patients using ORENCIA and 74.7% of those using adalimumab completed the study at Year 2

Primary Endpoint2

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

Selected Secondary Endpoint2

Proportion achieving remission* (DAS28-CRP <2.6)

*Remission is defined as DAS28-CRP <2.6.4 Clinical remission does not mean drug-free remission or complete absence of disease activity.

Key Limitations of the Study2

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.

Key Inclusion Criteria2,4

  • ≥18 years of age with moderate to severe active RA with a confirmed diagnosis 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 Criteria5

  • 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

anti-CCP, anti-cyclic citrullinated peptide; ESR, erythrocyte sedimentation rate;
RF, rheumatoid factor.

AMPLE 2-year included a broad patient population, with over half having poor prognostic factors2,3

Key baseline characteristics for the ORENCIA subcutaneous and methotrexate arm and the adalimumab subcutaneous and methotrexate arm. Key baseline characteristics for the ORENCIA subcutaneous and methotrexate arm and the adalimumab subcutaneous and methotrexate arm.

Baseline Characteristics2,3

  • Average age: 51.4 for ORENCIA-treated patients, 51 years for adalimumab-treated patients
  • Study reports did not always include detailed patient characteristic data for all individual patients. In patients for whom detailed characteristic data were available:
    • ORENCIA group (n=310): 62% had at least one comorbid condition, the most frequent being high blood pressure (42%) and high cholesterol (26%)
    • Adalimumab group (n=315): 55% had at least one comorbid condition, the most frequent being high blood pressure (38%)and high cholesterol (26%)

BMI, body mass index.

*Anti-CCP status was reported by patient’s medical history for 488 of the 646 patients at baseline.5

†In a post hoc analysis of serum collected for 508 of 646 patients at baseline, 74% of ORENCIA-treated patients and 79% of adalimumab-treated patients were anti-CCP+.6

‡Seropositive for RF antibodies as reported by patient’s medical history.2

§Radiographic evidence of joint erosions.2

Study reports did not always include detailed patient characteristic data for all individual patients.

#Comorbid conditions included high BMI, advancing age (65 or older), cardiovascular disease, high cholesterol, high blood pressure, and diabetes.3

Continue to AMPLE 2-Year safety results

Selected Important Safety Information

Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors:

Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult moderate to severe rheumatoid arthritis (RA) patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (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.

NORD-STAR

In moderate to severe, treatment-naïve, early RA patients with poor prognostic factors

ORENCIA was studied among 3 biologics vs active conventional therapy (ACT)7

NORD-STAR (N=795) was a 48-week, multicenter, randomized, blinded-assessor study in patients with early RA and seropositivity (RF+ or anti-CCP+) or CRP ≥10 mg/L and DAS28-CRP >3.2.7

Remission rates for 3 biologics vs active conventional therapy.

Co-primary Endpoints7

  • CDAI remission: CDAI ≤2.8 at 48 weeks
  • Change in radiographic score at 48 weeks

Selected Secondary Endpoint7

  • DAS remission: DAS28-CRP <2.6 at 48 weeks

Co-primary Endpoints7

Van der Heijde-modified Sharp Score (vdHSS)

ACT: 0.45 (0.31 to 0.59)
CTZ: 0.47 (0.33 to 0.61)
ORENCIA: 0.62 (0.48 to 0.76)
TCL: 0.50 (0.36 to 0.64)

Remission rates for 3 biologics vs ACT at 48 weeks (ITT)7*†

Remission rates for 3 biologics vs active conventional therapy.

Co-primary Endpoints7

Van der Heijde-modified Sharp Score (vdHSS)

ACT: 0.45 (0.31 to 0.59)
CTZ: 0.47 (0.33 to 0.61)
ORENCIA: 0.62 (0.48 to 0.76)
TCL: 0.50 (0.36 to 0.64)

CDAI, Clinical Disease Activity Index; CI, confidence interval; ITT, intent to treat.

*Clinical remission does not mean drug-free remission or complete absence of disease activity.4

†Oral prednisolone (tapered from 20 mg/day to 5 mg/day in 9 weeks and discontinuation after 9 months) or enterotablets sulfasalazine (2 g/day), hydroxychloroquine (35 mg/kg/week or 200 mg/day) and intra-articular triamcinolone hexacetonide injection (or equivalent) in all swollen joints at each visit (maximally 4 joints and 80 mg/visit).7

ORENCIA was studied in treatment-naïve, early RA patients with poor prognostic factors7

Patients were randomized into 4 treatment arms7

  1. ACT: prednisolone or triple therapy (MTX + csDMARDs) + glucocorticoids (n=200)*
  2. CTZ: certolizumab pegol SC 200 mg (400 mg at 0, 2, 4 weeks) (n=203)
  3. ORENCIA SC: 125 mg (n=204)
  4. TCL: tocilizumab IV 8 mg/kg/4 weeks or SC 162 mg/weekly (n=188)†

All patients received MTX starting on Day 1 (escalated to 25 mg/week within 4 weeks). MTX dose could be reduced in all treatment arms due to toxicity/intolerability, and subsequently re-escalated up to 20 mg/week.7

Key Inclusion Criteria7

  • 18 years or older
  • Symptom duration of <24 months
  • Poor prognostic factors:
    • Moderate-to-severe disease activity with DAS28-CRP >3.2
    • ≥2 (of 66) swollen and ≥2 (of 68) tender joints
    • RF+ or anti-CCP+ or CRP of ≥10 mg/L

Key Exclusion Criteria7

  • Previous treatment with a DMARD
  • Women nursing or pregnant
  • Inflammatory diseases other than RA

Limitations7

  • The ACT arm comprised 2 different treatment strategies based on national recommendations for conventional RA therapy in the individual countries
  • Analyses were adjusted for country effects, whereas the study was not powered for subgroup analyses
  • The open-label design may influence certain subjective outcomes

csDMARDs, conventional synthetic DMARDs; DMARD, disease-modifying antirheumatic drug.

*Oral prednisolone (tapered from 20 mg/day to 5 mg/day in 9 weeks and discontinuation after 9 months) or enterotablets sulfasalazine (2 g/day), hydroxychloroquine (35 mg/kg/week or 200 mg/day), and intra-articular triamcinolone hexacetonide injection (or equivalent) in all swollen joints at each visit (maximally 4 joints and 80 mg/visit).7

†17 Finnish patients randomized to arm 4 (tocilizumab + MTX) but not receiving it due to unavailability are not included. They were excluded from the ITT population to allow a fair analysis of the efficacy of tocilizumab. Robustness analyses showed comparable results.7

Baseline characteristics for 3 biologic therapies and active conventional therapy. Baseline characteristics for 3 biologic therapies and active conventional therapy.

SD, standard deviation.

Continue to NORD-STAR safety results

Selected Important Safety Information

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

AGREE

In moderate to severe MTX-naïve* RA patients with almost half having comorbid conditions

Remission and radiographic progression were studied in a registrational trial1

AGREE was a 12-month, multinational, placebo-controlled, randomized, double-blind, Phase IIIb study of MTX-naïve patients (n=509). Adult patients were randomized to ORENCIA IV + MTX (n=256) or placebo + MTX (n=253).1

49% of ORENCIA patients and 43% of placebo patients had ≥1 comorbid condition8†

Significantly improved remission rates‡ and radiographic progression in treatment-naïve patients1

Co-primary endpoints at 1 year1

509 methotrexate-naïve patients were randomized to recieve ORENCIA infusion and methotrexate or placebo and methotrexate.

Co-primary Endpoints1

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

Selected Secondary Endpoint1

  • ACR 50 response at 12 months

Selected Endpoint at 12 Months1

  • ACR 20/70 responses

Comorbid conditions8

In the ORENCIA arm, 49% had ≥1 comorbid condition, the most common being hypertension (33%). In the placebo arm, 43% had ≥1 comorbid condition, hypertension again being the most common (32%). 9% of ORENCIA patients and 11% in the placebo arm had high cholesterol.

Significantly improved remission rates‡ and radiographic progression in treatment-naïve patients1

Co-primary endpoints at 1 year1

Selected endpoints: ORENCIA IV + MTX significantly
improved ACR 20, 50 and 70 responses at 1 year1,9

Co-primary endpoints at 1 year were remission, achieved by 41% of ORENCIA and 23% of placebo patients, and radiographic progression, which was 0.6 for the ORENCIA group and 1.1 for the placebo group.

Selected endpoints: ORENCIA IV + MTX significantly
improved ACR 20, 50 and 70 responses at 1 year1,9

Line graph of selected endpoints at 1 year: ACR 20 was 76% in the ORENCIA arm and 62% for placebo, ACR 50 was 57% in the ORENCIA arm and 42% for the placebo arm, and ACR 70 was 43% for the ORENCIA arm and 27% for the placebo arm.

TSS, Total Sharp Score.

*Or prior exposure to MTX ≤10 mg/week for ≤3 weeks with none administered for 3 months prior to enrollment.1

†This study was not powered to detect differences in response based oncomorbid conditions.

‡Remission is defined as DAS28-CRP <2.6.1 Clinical remission does not mean drug-free remission or complete absence of disease activity.

§Missing data for the as-observed population at 6 months were imputed by linear extrapolation at 1 year.1

Day 29 was an exploratory endpoint.9

Study Design7

Patients were randomly assigned to treatment groups. ORENCIA IV (~10 mg/kg based on patient weight) plus MTX and placebo given with MTX were 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.1

509 methotrexate-naïve patients were randomized to recieve ORENCIA infusion and methotrexate or placebo and methotrexate.

Baseline Characteristics1

  • 89% of patients were anti-CCP+
  • 96.5% were RF+
  • Mean disease duration: 6.5 months
  • Mean DAS28-CRP: 6.3

Key Exclusion Criteria1

  • 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
  • Radiographic evidence of bone erosion of the hands, wrist, and feet

AGREE is one of the 6 registrational trials for ORENCIA; the safety experience of these patients at 1 year was consistent with that of the other 5 trials.1,10
Please refer to the Pooled Safety and Full Prescribing Information.

Continue to Pooled safety results
ATTAIN

ORENCIA IV + DMARDs in TNFi-IR patients with moderate to severe RA

Patients with long disease duration and previous treatment failure saw improved symptom relief and physical function with ORENCIA11,12

ATTAIN was a 6-month, randomized, double-blind, Phase III, placebo-controlled trial of ORENCIA in patients with inadequate response to ≥3 months of TNFi therapy. 55% of patients had ≥1 comorbid condition.

Co-primary endpoint:
Symptom improvement at 6 months11

Co-primary endpoint: symptom improvement at 6 months. Co-primary endpoint: symptom improvement at 6 months.

∆ 30.9% (P<0.001)

Co-primary endpoint: Improved physical function at 6 months11
Patients with a ≥0.3 HAQ-DI improvement

(P<0.001)

Co-primary endpoint: Improved physical function at 6 months.

Safety: ATTAIN is one of the 6 registrational trials for ORENCIA; the safety experience of these patients at 6 months was consistent with that of the other 5 trials.10,11

Please refer to the Pooled Safety and Full Prescribing Information.

Co-primary endpoint: Improved physical function at 6 months11
Patients with a ≥0.3 HAQ-DI improvement

(P<0.001)

Co-primary endpoint: Improved physical function at 6 months.

DMARDs, disease-modifying antirheumatic drug; TNFi, tumor necrosis factor inhibitor; TNFi-IR, inadequate response to TNFi therapy; HAQ-DI, Health Assessment
Questionnaire-Disability Index.

*Of these 258 patients, 1 did not meet the inclusion criteria and 1 withdrew for other reasons, leaving 256 patients in the ORENCIA IV + nonbiologic DMARD arm.11

ORENCIA was studied in TNFi-IR patients11

391 patients were randomized 2:1 to receive ORENCIA IV 10 mg/kg + DMARDs (n=258)* or placebo + DMARDs (n=133).† ORENCIA or placebo was given on Days 1, 15, and 29 and every 4 weeks thereafter, up to and including Day 141.1

Inclusion Criteria10

  • ≥18 years of age with active RA for ≥1 year
  • Inadequate response to anti-TNFα therapy (etanercept, infliximab, or both at approved dose)‡ after ≥3 months of treatment and discontinued before randomization
  • ≥12 tender and ≥10 swollen joints, CRP ≥1 mg/dL at randomization
  • Had been taking oral DMARD or anakinra for ≥3 months, with stable dose for ≥28 days

Baseline Characteristics11,12

  • Disease duration: ORENCIA 12.2 years; placebo 11.4 years
  • Mean DAS28-CRP: 6.5
  • 73.3% of ORENCIA patients and 72.9% of placebo patients were RF+
  • 55% of patients had ≥1 comorbid condition
  • High blood pressure was the most common comorbid condition in both treatment arms (ORENCIA, 38%; placebo, 31%)
  • 12% of ORENCIA patients and 10% in the placebo arm had high cholesterol

*Of these 258 patients, 1 did not meet the inclusion criteria and 1 withdrew for other reasons, leaving 256 patients in the ORENCIA IV + nonbiologic DMARD arm.11

† 75.6% and 82.0% of patients continued on MTX in the ORENCIA IV and placebo arms, respectively. Other DMARDs used in ≥5% of patients in both treatment arms included hydroxychloroquine, leflunomide, and sulfasalazine.11

‡ Some patients received adalimumab.11

See ORENCIA Pooled Safety Results

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.

ACTION

The efficacy of ORENCIA was consistent regardless of BMI13

ACTION was a 2-year,* non-interventional, international, prospective study that evaluated ORENCIA retention rates in both biologic-naïve and csDMARD-IR patients. In this subgroup analysis, the effect of BMI on the clinical efficacy and retention rate of ORENCIA was evaluated at 6 months in biologic-naïve patients according to their baseline BMI.

EULAR responses to ORENCIA stratified by BMI. EULAR responses to ORENCIA stratified by BMI.

csDMARD-IR, inadequate response to conventional synthetic disease-modifying antirheumatic drug; EULAR, European Alliance of Associations for Rheumatology.

*2-year study included 2359 patients, with 672 patients identified as biologic naïve. Of these patients, BMI data were available for 643 patients.13

†Moderate response: DAS28-CRP >3.2 and ≤5.1; reduction >0.6 to ≤1.2.14

‡Good response: DAS28-CRP ≤3.2; reduction of >1.2.14

~80% of patients had a moderate† or good‡ EULAR response at 6 months13

Study Design13

The Abatacept in Routine Clinical Practice (ACTION) study was a non-interventional, 2-year, international (Europe and Canada), prospective study in patients who started treatment with ORENCIA IV during routine clinical practice from May 2008 to December 2013. This study evaluated the clinical efficacy and retention for ORENCIA IV as a first-line biologic at 6 months according to patients’ baseline BMI using EULAR response criteria (DAS28-CRP at 6 months). Retention rates were estimated by Kaplan-Meier survival analysis.

Inclusion Criteria13

  • Biologic-naïve
  • BMI measured at baseline
  • All patients were aged ≥18 years
  • Had an established diagnosis of moderate to severe disease according to the 1987 ACR criteria
  • Were not already participating in an interventional clinical trial for RA

Limitations13

  • Observational in nature
  • Lack of active comparator
  • Subgroup analysis of a larger study
  • Potential for referral and channeling bias
  • The obese subgroup had higher disease activity at baseline, which is a potential limitation of the results

csDMARD-IR, inadequate response to conventional synthetic disease-modifying antirheumatic drug; EULAR, European Alliance of Associations for Rheumatology.

*2-year study included 2359 patients, with 672 patients identified as biologic naïve. Of these patients, BMI data were available for 643 patients.13

†Moderate response: DAS28-CRP >3.2 and ≤5.1; reduction >0.6 to ≤1.2.14

‡Good response: DAS28-CRP ≤3.2; reduction of >1.2.14

Continue to ORENCIA Pooled Safety Results

Important Safety Information
for ORENCIA® (abatacept)

Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult moderate to severe rheumatoid arthritis (RA) patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (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 Reactions: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). In postmarketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

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

Immunizations: Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. ORENCIA-treated patients may receive current non-live vaccines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.

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

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

Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT): Post-Transplant Lymphoproliferative Disorder (PTLD) occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 4 patients (3.4%) experienced PTLD. All the PTLD events were associated with Epstein-Barr virus (EBV) infection. The range of time to onset of the event was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Before administering ORENCIA, provide recommended prophylaxis for EBV infection and continue for 6 months post-transplantation to prevent EBV-associated PTLD. Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7% (n=8) experienced CMV invasive diseases up to day 225 post-transplant. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract. Monitor patients for CMV infection/reactivation for 6 months post-transplant regardless of the results of donor and recipient pre-transplant CMV serology. Consider prophylaxis for CMV infection/reactivation during treatment and for six months following HSCT.

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

Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 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: In controlled clinical trials, adult RA patients experienced serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo). In the GVHD-1 study, serious adverse reactions reported in >5% of patients who received ORENCIA in combination with a calcineurin inhibitor and methotrexate included pyrexia (20%), pneumonia (8%), acute kidney injury (7%), diarrhea (6%), hypoxia (5%), and nausea (5%).

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

Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of pJIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in pediatric pJIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients. The most frequent adverse reactions of all grades reported in ≥10% of patients with aGVHD who received ORENCIA with a difference of ≥2% for the 7/8 cohort, 8/8 cohort ORENCIA arm, and 8/8 cohort placebo arm, respectively, were anemia (56%, 69%, and 57%), CD4 lymphocytes decreased (14%, 14%, and 9%), hypertension (49%, 43%, and 38%), pyrexia (28%, 19%, and 20%), CMV reactivation/CMV infection (26%, 32%, and 22%), pneumonia (19%, 12%, and 10%), epistaxis (12%, 16%, and 10%), acute kidney injury (9%, 15%, and 10%), and hypermagnesemia (5%, 18%, 10%).

Incidence rates of grade 3 or 4 adverse reactions were the same as incidence rates of all grades, with the exception of grade 3 or 4 pyrexia in all arms (9% [7/8 cohort], 10% [8/8 cohort, ORENCIA arm], and 4% [8/8 cohort, placebo arm]), pneumonia in the 8/8 cohort placebo arm (9%) and acute kidney injury in the 7/8 cohort ORENCIA arm (7%). Clinically relevant adverse reactions in <10% of patients who received ORENCIA in combination with calcineurin inhibitor and methotrexate in Study GVHD-1 included EBV reactivation.

Note concerning ORENCIA administration options: ORENCIA may be administered as an intravenous infusion only for patients 6 years of age and older. PJIA or pediatric PsA patients may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determines it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested. ORENCIA for the prophylaxis of aGVHD in patients undergoing HSCT may only be administered as an intravenous (IV) infusion. The safety and effectiveness of ORENCIA have not been established in pediatric patients younger than 2 years of age for prophylaxis of aGVHD.

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References: 1. 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. doi:10.1136/ard.2008.101121. 2. 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. doi:10.1136/annrheumdis-2013-203843. 3. Data on File. REF-01226-427. Princeton, NJ: Bristol Myers Squibb. 4. 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. doi:10.1002/art.37711. 5. Data on File. ABAT 143. Princeton, NJ: Bristol Myers Squibb. 6. Sokolove J, Schiff M, Fleischmann R, et al. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis. 2016;75(4):709-714. doi:10.1136/annrheumdis-2015-207942. 7. Østergaard M, van Vollenhoven RF, Rudin A, et al. Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. Ann Rheum Dis. 2023;82(10):1286-1295. doi:10.1136/ard-2023-224116. 8. Data on File. REF-01227-427. Princeton, NJ: Bristol Myers Squibb. 9. Data on File. ABAT 032. Princeton, NJ: Bristol Myers Squibb. 10. ORENCIA® [package insert]. Princeton, NJ: Bristol Myers Squibb. 11. Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition [published correction appears in N Engl J Med. 2005 Nov 24;353(21):2311]. N Engl J Med. 2005;353(11):1114-1123. doi:10.1056/NEJMoa050524. 12. Data on File. REF-01228-427. Princeton, NJ: Bristol Myers Squibb. 13. Mariette X, Alten R, Nüßlein HG, et al. The effect of body mass index on clinical response to abatacept as a first-line biologic for rheumatoid arthritis: 6-month results from the 2-year, observational, prospective ACTION study. Joint Bone Spine. 2017;84(5):571-576. doi:10.1016/j.jbspin.2016.10.011. 14. Van Gestel AM, Anderson JJ, van Riel PLCM, et al. ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. J Rheumatol. 1999;26(3):705-711.