Our Passion for patient care never rests

ENBREL EFFICACY FOR ADULT MODERATE TO SEVERE RHEUMATOID ARTHRITIS

Our passion for patient care never rests

ENBREL can reduce signs and symptoms, induce major clinical response, inhibit the progression of structural damage, and improve physical function for your patients with moderate to severe rheumatoid arthritis (RA). ENBREL can be used in combination with methotrexate (MTX) or used alone.1

Watch how patients could benefit from ENBREL
Watch how ENBREL monotherapy could help your patients

The COMET study

COMET was a 24-month, multicenter, randomized, double-blind, 2-period study of 542 patients with moderately to severely active early RA (from ≥3 months to ≤2 years' duration) with mean disease duration of 9 months and naïve to methotrexate or ENBREL.2

View full study design

Reduction in pain, stiffness, and CRP

Together, we can help patients feel less pain and reduce morning stiffness

  • Some patients treated with ENBREL + MTX experienced significant improvements in select signs and symptoms and ACR response at Week 2 and out to Year 23*
  • At 2 Weeks:
    • Patients felt >3x more reduction in pain by taking ENBREL+MTX rather than taking MTX alone
    • Morning stiffness was reduced by nearly 3 hours from baseline
    • Patients had >5x more reduction in CRP by taking ENBREL+MTX rather than taking MTX alone§
  • ACR 20 responses for the ENBREL + MTX group vs MTX alone were 49% vs 14%, respectively, at Week 2 and 86% vs 61%, respectively, at Year 2 nonresponder imputation (NRl)3

The COMET study was divided into 2 parts. The Year 2 population must have finished Year 1 and had at least 1 visit in Year 2.3

ENBREL + MTX demonstrated a mean reduction of 28 mm on a visual pain scale at Week 2 compared to 8 mm for MTX alone.3

Morning stiffness at baseline was 363 min for ENBREL + MTX and 382 min for MTX.3

The numbers of patients for the CRP analysis were ENBREL + MTX=107 and MTX=91.3

Together, we can help patients feel less pain and reduce morning stiffness

Reduction in pain, stiffness, and CRP

  • Some patients treated with ENBREL + MTX experienced significant improvements in select signs and symptoms and ACR response at Week 2 and out to Year 23*
  • At 2 Weeks:
    • Patients felt >3x more reduction in pain by taking ENBREL+MTX rather than taking MTX alone
    • Morning stiffness was reduced by nearly 3 hours from baseline
    • Patients had >5x more reduction in CRP by taking ENBREL+MTX rather than taking MTX alone§
  • ACR 20 responses for the ENBREL + MTX group vs MTX alone were 49% vs 14%, respectively, at Week 2 and 86% vs 61%, respectively, at Year 2 nonresponder imputation (NRl)3

The COMET study was divided into 2 parts. The Year 2 population must have finished Year 1 and had at least 1 visit in Year 2.3

ENBREL + MTX demonstrated a mean reduction of 28 mm on a visual pain scale at Week 2 compared to 8 mm for MTX alone.3

Morning stiffness at baseline was 363 min for ENBREL + MTX and 382 min for MTX.3

The numbers of patients for the CRP analysis were ENBREL + MTX=107 and MTX=91.3

Percentage of patients who achieved HAQ ≤0.5 (LOCF)3,4,*

Together, we can help patients get back to their everyday activities

  • The majority of ENBREL + MTX patients achieved a HAQ score consistent with the general population (≤0.5)3,4*
  • Mean HAQ score at baseline was 1.65 in the MTX arm (n=94), 1.62 in the ENBREL + MTX → ENBREL arm (n=108), and 1.76 in the ENBREL + MTX arm (n=108). At Year 2, mean HAQ score was 0.79 in the MTX arm, 0.65 in the ENBREL + MTX → ENBREL arm, and 0.58 in the ENBREL + MTX arm3

HAQ score of ≤0.5 is consistent with the score of the general population.3

Patients were randomly assigned to 1 of 4 treatment groups (Group 1A, 1B, 2A, or 2B) at the beginning of the study. During Year 1 of the study, Groups 1A and 1B were combined in the ENBREL + MTX treatment arm, and Groups 2A and 2B were combined in the MTX treatment arm. Not all subjects randomized to Year 2 groups were present in the Year 2 efficacy population, due to withdrawals during Year 1. See Study Design for more information about the Year 1 and Year 2 study populations.

The data points shown at Year 1 represent results for combined study arms (Group 1A + Group 1B and Group 2A + Group 2B) reported at the end of Year 1 treatment. For the study populations entering Year 2 of treatment, the percentages of patients who had achieved HAQ ≤0.5 at the Year 1 time point were 57%, 62%, 51%, and 43% in Groups 1A, 1B, 2A, and 2B respectively.

Together, we can help patients get back to their everyday activities

Percentage of patients who achieved HAQ ≤0.5 (LOCF)3,4,*

  • The majority of ENBREL + MTX patients achieved a HAQ score consistent with the general population (≤0.5)3,4*
  • Mean HAQ score at baseline was 1.65 in the MTX arm (n=94), 1.62 in the ENBREL + MTX → ENBREL arm (n=108), and 1.76 in the ENBREL + MTX arm (n=108). At Year 2, mean HAQ score was 0.79 in the MTX arm, 0.65 in the ENBREL + MTX → ENBREL arm, and 0.58 in the ENBREL + MTX arm3

HAQ score of ≤0.5 is consistent with the score of the general population.3

Patients were randomly assigned to 1 of 4 treatment groups (Group 1A, 1B, 2A, or 2B) at the beginning of the study. During Year 1 of the study, Groups 1A and 1B were combined in the ENBREL + MTX treatment arm, and Groups 2A and 2B were combined in the MTX treatment arm. Not all subjects randomized to Year 2 groups were present in the Year 2 efficacy population, due to withdrawals during Year 1. See Study Design for more information about the Year 1 and Year 2 study populations.

The data points shown at Year 1 represent results for combined study arms (Group 1A + Group 1B and Group 2A + Group 2B) reported at the end of Year 1 treatment. For the study populations entering Year 2 of treatment, the percentages of patients who had achieved HAQ ≤0.5 at the Year 1 time point were 57%, 62%, 51%, and 43% in Groups 1A, 1B, 2A, and 2B respectively.

Percentage of patients who achieved DAS 28 clinical remission

Together, we can help patients achieve clinical remission

  • Some patients treated with ENBREL + MTX experienced rapid and sustained DAS 28 remission by Week 4 and out to Year 23*
  • Nearly half of patients reached clinical remission at Week 243
  • DAS 28 clinical remission was achieved by 50% of patients in the ENBREL + MTX → ENBREL group (n=108) and 58% in the MTX → ENBREL + MTX group (n=88) at Year 23
  • DAS 28 clinical remission does not mean drug-free remission or complete absence of disease

Disease activity score (DAS) 28 clinical remission is defined as a DAS <2.6 units. Calculation of DAS 28 utilizes tenderness scores (Ritchie Articular Index), swollen joint count, erythrocyte sedimentation rate (ESR), and visual analog scale (VAS) from a patient´s general health assessment. The DAS 28 is a validated tool used in clinical trials and serves as the basis for the EULAR response criteria.3,5

Together, we can help patients achieve clinical remission

  • Some patients treated with ENBREL + MTX experienced rapid and sustained DAS 28 remission by Week 4 and out to Year 23*

Percentage of patients who achieved DAS 28 clinical remission

  • Nearly half of patients reached clinical remission at Week 243
  • DAS 28 clinical remission was achieved by 50% of patients in the ENBREL + MTX → ENBREL group (n=108) and 58% in the MTX → ENBREL + MTX group (n=88) at Year 23
  • DAS 28 clinical remission does not mean drug-free remission or complete absence of disease

Disease activity score (DAS) 28 clinical remission is defined as a DAS <2.6 units. Calculation of DAS 28 utilizes tenderness scores (Ritchie Articular Index), swollen joint count, erythrocyte sedimentation rate (ESR), and visual analog scale (VAS) from a patient´s general health assessment. The DAS 28 is a validated tool used in clinical trials and serves as the basis for the EULAR response criteria.3,5

Mean change in modified Total Sharp Score (mTSS)

Together, we can help limit joint damage

  • ENBREL is proven in combination, and strong enough to stand alone when needed6,7
  • At Year 2, the percentage of patients achieving ACR 20 was 86% in the ENBREL + MTX arm, 80% in the ENBREL + MTX → ENBREL arm, and 61% in the MTX arm NRI3

1 subject did not have a valid radiograph at Week 52 but did at baseline and Week 104; change from Week 52 to Week 104 cannot be assessed.7

Together, we can help limit joint damage

  • ENBREL is proven in combination, and strong enough to stand alone when needed6,7

Mean change in modified Total Sharp Score (mTSS)

  • At Year 2, the percentage of patients achieving ACR 20 was 86% in the ENBREL + MTX arm, 80% in the ENBREL + MTX → ENBREL arm, and 61% in the MTX arm NRI3

1 subject did not have a valid radiograph at Week 52 but did at baseline and Week 104; change from Week 52 to Week 104 cannot be assessed.7

The TEMPO study

The TEMPO study was a 36-month, multicenter, randomized, double-blind study of 682 patients with moderately to severely active RA with mean disease duration of 7 years who had an inadequate response to at least 1 prior DMARD, but were not refractory to MTX.8

View full study design

Together, we can help patients feel less pain and morning stiffness

  • ENBREL + MTX provided rapid and sustained improvements in clinical signs and symptoms as early as Week 2 and out to Year 39
  • ACR 20 responses (Nonresponder Imputation) for the ENBREL + MTX group vs MTX alone were 44% vs 19% at Week 2 and 52% vs 33% at Year 39

Together, we can help patients feel less pain and morning stiffness

  • ENBREL + MTX provided rapid and sustained improvements in clinical signs and symptoms as early as Week 2 and out to Year 39
  • ACR 20 responses (Nonresponder Imputation) for the ENBREL + MTX group vs MTX alone were 44% vs 19% at Week 2 and 52% vs 33% at Year 39

Reductions in HAQ scores

Percentage of patients who achieved HAQ ≤0.5 (LOCF)8†

Together, we can help patients get back to their everyday activities

  • ENBREL + MTX provided rapid and sustained improvements in HAQ scores by Week 2 and out to Year 38
  • Mean HAQ score at baseline, Week 2, and Year 3 were 1.7, 1.5, and 1.1 in the MTX arm and 1.8, 1.3, and 0.8 in the ENBREL + MTX arm, respectively8
  • Half of ENBREL patients achieved a HAQ score consistent with the general population (≤0.5)8†
  • Mean HAQ score at baseline was 1.70 in the MTX arm (n=228) and 1.76 in the ENBREL + MTX arm (n=231). At Year 3, mean HAQ score was 1.1 in the MTX arm and 0.8 in the ENBREL + MTX arm8
  • A higher percentage of patients treated with ENBREL and ENBREL + MTX achieved ACR 20, ACR 50, and ACR 70 responses and Major Clinical Responses than in the comparison groups

HAQ score of ≤0.5 is consistent with the score of the general population.10

Major Clinical Response is achieving an ACR 70 response for a continuous 6-month period.

Together, we can help patients get back to their everyday activities

  • ENBREL + MTX provided rapid and sustained improvements in HAQ scores by Week 2 and out to Year 38

Reductions in HAQ scores

  • Mean HAQ score at baseline, Week 2, and Year 3 were 1.7, 1.5, and 1.1 in the MTX arm and 1.8, 1.3, and 0.8 in the ENBREL + MTX arm, respectively8
  • Half of ENBREL patients achieved a HAQ score consistent with the general population (≤0.5)8†

Percentage of patients who achieved HAQ ≤0.5 (LOCF)8†

  • Mean HAQ score at baseline, Week 2, and Year 3 were 1.7, 1.5, and 1.1 in the MTX arm and 1.8, 1.3, and 0.8 in the ENBREL + MTX arm, respectively8
  • Half of ENBREL patients achieved a HAQ score consistent with the general population (≤0.5)8†
  • Mean HAQ score at baseline was 1.70 in the MTX arm (n=228) and 1.76 in the ENBREL + MTX arm (n=231). At Year 3, mean HAQ score was 1.1 in the MTX arm and 0.8 in the ENBREL + MTX arm8
  • A higher percentage of patients treated with ENBREL and ENBREL + MTX achieved ACR 20, ACR 50, and ACR 70 responses and Major Clinical Responses than in the comparison groups

HAQ score of ≤0.5 is consistent with the score of the general population.10

Major Clinical Response is achieving an ACR 70 response for a continuous 6-month period.

Percentage of patients who achieved DAS 28 clinical remission

Together, we can help patients achieve clinical remission

  • Some patients treated with ENBREL + MTX experienced rapid and sustained DAS 28 remission by Week 4 and out to Year 311
  • ACR 20/50/70 rates at Week 4 were 58%/20%/7% for ENBREL + MTX and 34%/4%/0% for MTX alone9
  • ACR 20/50/70 rates at Year 3 were 52%/43%/31% for ENBREL + MTX and 33%/24%/13% for MTX alone (NRI)9
  • DAS 28 clinical remission does not mean drug-free remission or complete absence of disease

Together, we can help patients achieve clinical remission

  • Some patients treated with ENBREL + MTX experienced rapid and sustained DAS 28 remission by Week 4 and out to Year 311

Percentage of patients who achieved DAS 28 clinical remission

  • ACR 20/50/70 rates at Week 4 were 58%/20%/7% for ENBREL + MTX and 34%/4%/0% for MTX alone9
  • ACR 20/50/70 rates at Year 3 were 52%/43%/31% for ENBREL + MTX and 33%/24%/13% for MTX alone (NRI)9
  • DAS 28 clinical remission does not mean drug-free remission or complete absence of disease

Mean change in modified Total Sharp Score (mTSS)

Together, we can help limit joint damage

  • Some patients treated with ENBREL + MTX or ENBREL monotherapy experienced significant inhibition of joint damage through Year 312*
  • ENBREL + MTX therapy and ENBREL monotherapy resulted in significantly less radiographic progression compared with MTX alone12
  • Patients with no radiographic progression (∆mTSS ≤0) at 3 years: 73% in the ENBREL + MTX arm, 60% on ENBREL alone and 50% on MTX alone12

Per protocol, in order to read the Year 3 data (N=638), the Year 1 (N=648) and Year 2 data (N=622) were reread. Because of the known variability in reading of the radiographic images in RA, all radiographs were reread and blinded to patient and time point by the 2 physicians who read the images for the Year 2 report. Thus, the Year 3 scoring of the radiographic images is considered a new reading of the Year 1 and Year 2 time points.12

Together, we can help limit joint damage

  • Some patients treated with ENBREL + MTX or ENBREL monotherapy experienced significant inhibition of joint damage through Year 312*

Mean change in modified Total Sharp Score (mTSS)

  • ENBREL + MTX therapy and ENBREL monotherapy resulted in significantly less radiographic progression compared with MTX alone12
  • Patients with no radiographic progression (∆mTSS ≤0) at 3 years: 73% in the ENBREL + MTX arm, 60% on ENBREL alone and 50% on MTX alone12

Per protocol, in order to read the Year 3 data (N=638), the Year 1 (N=648) and Year 2 data (N=622) were reread. Because of the known variability in reading of the radiographic images in RA, all radiographs were reread and blinded to patient and time point by the 2 physicians who read the images for the Year 2 report. Thus, the Year 3 scoring of the radiographic images is considered a new reading of the Year 1 and Year 2 time points.12

The STATWISE Program

A 12-week text-based symptom tracker developed for patients to help facilitate more meaningful discussions about signs and symptoms for those starting ENBREL.

Visit the STATWISE™ site for patients

ENBREL STATWISE program
Prescription Enbrel® (etanercept) is administered by injection.
IMPORTANT SAFETY INFORMATION AND INDICATIONS
SERIOUS INFECTIONS

Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.

In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown.

Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.

Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.

Pediatric Patients

In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin’s and non-Hodgkin’s lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.

NEUROLOGIC REACTIONS

Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.

CONGESTIVE HEART FAILURE

Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.

HEMATOLOGIC REACTIONS

Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.

HEPATITIS B REACTIVATION

Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients.

ALLERGIC REACTIONS

Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.

IMMUNIZATIONS

Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.

AUTOIMMUNITY

Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.

WEGENER’S GRANULOMATOSIS PATIENTS

The use of ENBREL in patients with Wegener’s granulomatosis receiving immunosuppressive agents (eg, cyclophosphamide) is not recommended.

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.

ADVERSE REACTIONS

The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials.

In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.

DRUG INTERACTIONS

The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.

Please see Prescribing Information and Medication Guide.

INDICATIONS

ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.

ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.

ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used with or without MTX.

ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.

References:

  • Enbrel® (etanercept) Prescribing Information, Immunex Corporation, Thousand Oaks, Calif. October/2017.
  • Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382.
  • Data on file, Amgen. COMET CSR 72719 2 yr Clinical. September 12, 2008.
  • Data on file, Amgen. COMET CSR 69344 1 yr Clinical. September 18, 2007.
  • Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol. 2005;23(suppl 39):S93-S99.
  • Data on file, Amgen. COMET CSR 73209 2 yr Radiographic. September 23, 2008.
  • Emery P, Breedveld FC, van der Heijde D, et al. Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study. Arthritis Rheum. 2010;62:674-682.
  • Data on file, Amgen. TEMPO CSR 57599 3 yr Clinical. June 21, 2005.
  • Data on file, Amgen. TEMPO CSR 57599 ACR NRI. February, 2005.
  • Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003;1:20.
  • Data on file, Amgen. TEMPO Biostatistic Analysis Memo DAS 28. May, 2012.
  • Data on file, Amgen. TEMPO CSR 57599 3 yr Radiographic. November 22, 2005.
Prescription Enbrel® (etanercept) is administered by injection.
IMPORTANT SAFETY INFORMATION AND INDICATIONS
SERIOUS INFECTIONS

Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.

In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown.

Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.

Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.

Pediatric Patients

In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin’s and non-Hodgkin’s lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.

NEUROLOGIC REACTIONS

Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.

CONGESTIVE HEART FAILURE

Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.

HEMATOLOGIC REACTIONS

Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.

HEPATITIS B REACTIVATION

Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients.

ALLERGIC REACTIONS

Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.

IMMUNIZATIONS

Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.

AUTOIMMUNITY

Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.

WEGENER’S GRANULOMATOSIS PATIENTS

The use of ENBREL in patients with Wegener’s granulomatosis receiving immunosuppressive agents (eg, cyclophosphamide) is not recommended.

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.

ADVERSE REACTIONS

The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials.

In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.

DRUG INTERACTIONS

The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.

Please see Prescribing Information and Medication Guide.

INDICATIONS

ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.

ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.

ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used with or without MTX.

ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.

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IMPORTANT SAFETY INFORMATION AND INDICATIONS: SERIOUS INFECTIONS

Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.

In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown.

Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.

Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.

Pediatric Patients

In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin’s and non-Hodgkin’s lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.

NEUROLOGIC REACTIONS

Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.

CONGESTIVE HEART FAILURE

Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.

HEMATOLOGIC REACTIONS

Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.

HEPATITIS B REACTIVATION

Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients.

ALLERGIC REACTIONS

Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.

IMMUNIZATIONS

Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.

AUTOIMMUNITY

Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.

WEGENER’S GRANULOMATOSIS PATIENTS

The use of ENBREL in patients with Wegener’s granulomatosis receiving immunosuppressive agents (eg, cyclophosphamide) is not recommended.

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.

ADVERSE REACTIONS

The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials.

In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.

DRUG INTERACTIONS

The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.

Please see Prescribing Information and Medication Guide.

INDICATIONS

ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.

ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.

ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone

ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.

  • See More
  • See More
IMPORTANT SAFETY INFORMATION AND INDICATIONS: SERIOUS INFECTIONS

Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.

In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown.

Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.

Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.

Pediatric Patients

In patients who initiated therapy at ≤18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin’s and non-Hodgkin’s lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.

NEUROLOGIC REACTIONS

Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (<0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in postmarketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.

CONGESTIVE HEART FAILURE

Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored.

HEMATOLOGIC REACTIONS

Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed.

HEPATITIS B REACTIVATION

Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients.

ALLERGIC REACTIONS

Allergic reactions associated with administration of ENBREL during clinical trials have been reported in <2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.

IMMUNIZATIONS

Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin.

AUTOIMMUNITY

Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops.

WEGENER’S GRANULOMATOSIS PATIENTS

The use of ENBREL in patients with Wegener’s granulomatosis receiving immunosuppressive agents (eg, cyclophosphamide) is not recommended.

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate to severe alcoholic hepatitis.

ADVERSE REACTIONS

The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials.

In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population.

DRUG INTERACTIONS

The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.

Please see Prescribing Information and Medication Guide.

INDICATIONS

ENBREL is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be initiated in combination with methotrexate (MTX) or used alone.

ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.

ENBREL is indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone

ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

ENBREL is indicated for the treatment of patients 4 years or older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.