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

  • 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 reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.

At the start, ENBREL can help patients improve signs and symptoms in as little as two weeks.1

Over time, ENBREL has been shown to inhibit further joint damage long-term through 5 years.2,3 Plus, ENBREL can be used with or without methotrexate (MTX).4

RA patients in the RISE registry with a baseline disease activity measure and a follow-up visit at 6 months*†

~1 in 2 patients were in moderate to high disease activity despite treatment with the same csDMARDs5


ACR guidelines include adding a TNF inhibitor in patients with moderate to high disease activity despite csDMARD therapy.6


Primary efficacy endpoints and results1,2,8

  • DAS 28 remission (DAS 28 <2.6) was achieved by 49.8% of patients with ENBREL + MTX vs 27.8% with MTX at Week 52 (P<0.001)
  • Change from baseline in modified Total Sharp Score (mTSS) at 52 weeks was 0.27 for ENBREL + MTX vs 2.44 for MTX (P<0.001)

Additional efficacy endpoints and results1

  • ACR 20 was achieved by 86% of patients with ENBREL + MTX vs 67% of patients with MTX at Year 1 (P<0.001)
  • ACR 70 was achieved by 48% of patients with ENBREL + MTX vs 28% of patients with MTX at Year 1 (P<0.001)

View full study design

The COMET study of moderately to severely active early RA

Strong at the start: ENBREL + MTX can help your patients achieve clinical remission

  • 50% of patients taking ENBREL + MTX achieved DAS 28 remission vs. 28% of patients taking MTX at Year 11

Clinical remission was observed in 7 out of 10 patients when treated earlier (post hoc analysis)10

  • In a post hoc analysis, observed data were analyzed by baseline disease duration (very early RA: ≤4 months, early RA: 4 months to 2 years) and by treatment group (ENBREL + MTX and MTX alone). COMET was not prospectively designed to compare patient with very early RA to those with early RA10
  • 70% of ENBREL + MTX patients (n=63) treated very early vs 35% of MTX patients (n=49) treated very early achieved DAS 28 remission at Year 110
  • Baseline mean DAS 28 scores in patients with very early RA were 6.6 for the ENBREL + MTX arm and 6.7 for the MTX arm10
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn. Interpretation of the results of post hoc analysis is limited
   Clinical remission does not mean drug-free remission or complete absence of disease.

The COMET study of moderately to severely active early RA

ENBREL + MTX delivers fast symptom improvement and helps stop radiographic progression

Significant symptom improvement as early as Week 2 and out to Year 1 vs MTX alone (LOCF)1

 

5x improvement in morning stiffness duration (at week 2)

Week 2: 45% improvement with ENBREL + MTX vs 9% with MTX alone

Year 1: 66% improvement with ENBREL + MTX vs 41% with MTX alone

 

4x improvement in total tender joints (at week 2)

Week 2: 39% improvement with ENBREL +
MTX vs 10% with MTX alone

Year 1: 78% improvement with ENBREL + MTX
vs 59% with MTX alone

 

>6x improvement in CRP (at week 2)

Week 2: 71% improvement with ENBREL + MTX vs 11% with MTX alone

Year 1: 78% improvement with ENBREL + MTX vs 56% with MTX alone

 

>3x reduction in pain (at week 2)§

Week 2: 41% improvement with ENBREL +
MTX vs 12% with MTX alone

Year 1: 64% improvement with ENBREL + MTX
vs 48% with MTX alone

 

>2x improvement in total swollen joints (at week 2)

Week 2: 42% improvement with ENBREL +
MTX vs 19% with MTX alone

Year 1: 85% improvement with ENBREL + MTX
vs 66% with MTX alone

ENBREL 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)1, 11**
  • 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 arm11¶¶

The COMET study of moderately to severely active early RA

ENBREL + MTX helps stop further progression of joint damage by Year 1


75% of patients taking ENBREL + MTX had no progression of joint damage at Year 1 vs 54% of patients taking MTX alone (n=230)2***


  • 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 NRI11

In moderately to severely active RA

ENBREL + MTX helps patients achieve clinical remission

Some patients treated with ENBREL + MTX experienced rapid and sustained DAS 28 remission by Week 4 and out to Year 313

  • ACR 20/50/70 rates at Week 4 were 58%/20%/7% for ENBREL + MTX and 34%/4%/0% for MTX alone14
  • ACR 20/50/70 rates at Year 3 were 52%/43%/31% for ENBREL + MTX and 33%/24%/13% for MTX alone (NRI)14
  • DAS 28 clinical remission does not mean drug-free remission or complete absence of disease15

In moderately to severely active RA

ENBREL + MTX helps patients feel less joint pain and morning stiffness

Reductions in pain, morning stiffness and C-reactive protein (CRP)

Reductions in pain, morning stiffness, and C-reactive protein (CRP)

Reductions in pain, morning stiffness, and C-reactive protein (CRP)

Rapid Results by Week 2
Sustained results out to Year 3
  • ENBREL + MTX provided rapid and sustained improvements in clinical signs and symptoms as early as Week 2 and out to Year 314
  • 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 314

In moderately to severely active RA

ENBREL + MTX 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 316
  • 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, respectively16

  • Half of ENBREL patients achieved a HAQ score consistent with the general population (≤0.5)16¶
  • 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 arm16
  • 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 groups4††

In moderately to severely active RA

ENBREL + MTX can help stop the progression of joint damage

  • Some patients treated with ENBREL + MTX or ENBREL monotherapy experienced significant inhibition of joint damage through Year 318***
  • ENBREL + MTX therapy and ENBREL monotherapy resulted in significantly less radiographic progression compared with MTX alone18
  • Patients with no radiographic progression (Δ mTSS ≤0) at 3 years: 73% in the ENBREL + MTX arm, 60% on ENBREL alone and 50% on MTX alone18

Primary efficacy endpoints and results22,23

  • ACR-N area under the curve was 15.3 with ENBREL vs 11.5 with MTX at Month 6 (P=0.002)
  • Change from baseline in mTSS was 1.00 with ENBREL vs 1.59 with MTX at Year 1 (P=0.11)

OLE overview and limitations3,19,21

  • Patients who completed at least 1 year in the ERA randomized controlled trial (RCT) study were eligible for enrollment into OLE
  • MTX could be continued or started as necessary in the OLE at the investigator's discretion
  • All statistical analyses conducted during the OLE are considered descriptive and not confirmatory, and therefore are not presented in this piece
  • Consider the following limitations when evaluating OLE results
    • There is no concurrent control arm, limiting the estimate of treatment effect
    • Data are based only on patients who continued taking ENBREL at each year. Reasons for discontinuation included lack of tolerability, lack of efficacy, and loss to follow-up. Response rates may represent an enriched proportion of patients with continued efficacy and tolerability

View full study design

The ERA study of moderately to severely active early RA

Strong over time: long-term inhibition of further joint damage through Year 5

Patients treated up to 1 year

  • Change from baseline in mTSS was 1.00 with ENBREL vs 1.59 with MTX at Year 1 (P=0.11)23
  • 48% of the original patients treated with ENBREL were evaluated radiographically at 5 years3

The ERA study of moderately to severely active early RA

Results over time: lower MTX and corticosteroid use

Percent of ENBREL patients who reduced or discontinued MTX and corticosteroids3

  • Continued durable responses were seen for over 60 months in OLE treatment studies when patients received ENBREL without interruption. A substantial number of patients who initially received concomitant MTX or corticosteroids were able to reduce their doses or discontinue these concomitant therapies while maintaining their clinical responses3

Mean dose reductions of MTX and corticosteroids in ENBREL patients3

  • Among 110 patients who received MTX during the first 2 years of the study and who switched to ENBREL during the long-term OLE, 71 were able to discontinue and 20 were able to decrease their dose, 14 maintained their dose, and 5 increased their dose after 3 years in OLE3
  • At 5 years, 44 of 162 patients receiving ENBREL in both the RCT and OLE had also received corticosteroids during the study. Of those 44 patients, 27 were able to discontinue, 6 were able to decrease their dose, 10 maintained their dose, and 1 increased their dose3

A 10-year post hoc analysis of the ERA study of moderately to severely active early RA20

Limitations of DAS 28 results and OLE
  • DAS 28 was retrospectively calculated based on data collected during the study
  • DAS 28 was not prespecified endpoint in the controlled portion of the study and was calculated post hoc for each study period from baseline to 10 years
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn
  • There is no concurrent control arm, limiting the estimate of treatment effect
  • Data are based only on patients who continued taking ENBREL at each year. Reasons for discontinuation included lack of tolerability, lack of efficacy, and loss to follow-up. Response rates may represent an enriched proportion of patients with continued efficacy and tolerability

The Enbrel Mini® single-dose prefilled cartridge with AutoTouch® reusable autoinjector was designed with patients in mind.

Learn more about the latest innovation from ENBREL

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:

  1. Data on file, Amgen. COMET CSR 69344 1 yr Clinical. September 18, 2007.
  2. Data on file, Amgen; COMET CSR 71630 1 yr x-ray: December 7, 2007.
  3. Data on file, Amgen; 1623 ERA 5 yr: October 20, 2003.
  4. Enbrel® (etanercept) Prescribing Information, Immunex Corporation, Thousand Oaks, Calif.
  5. Data on file, Amgen; ACR RISE Registry analytics: May 9, 2017.
  6. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1-26.
  7. 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.
  8. Emery P, Breedveld FC, van der Heijde D, et al; for the Combination of Methotrexate and Etanercept in Early Rheumatoid Arthritis Trial Group. Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomised study. Arthritis Rheum. 2010;62:674-682.
  9. Data on file, Amgen; COMET Safety Population: 2009.
  10. Emery P, Kvien TK, Combe B, et al. Combination etanercept and methotrexate provides better disease control in very early (≤4 months) versus early rheumatoid arthritis (>4 months and <2 years): post hoc analyses from the COMET study. Ann Rheum Dis. 2012;71:989-992.
  11. Data on file, Amgen. COMET CSR 72719 2 yr Clinical. September 12, 2008.
  12. Klareskog L, van der Heijde D, de Jager JP, et al; for the TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-681.
  13. Data on file, Amgen. TEMPO Biostatistic Analysis Memo DAS 28. May, 2012.
  14. Data on file, Amgen. TEMPO CSR 57599 ACR NRI. February, 2005.
  15. Mäkinen H, Hannonen P, Sokka T. Definitions of remission for rheumatoid arthritis and review of selected clinical cohorts and randomised clinical trials for the rate of remission. Clin Exp Rheumatol. 2006;24:S-22-S-28.
  16. Data on file, Amgen; TEMPO CSR 57599 3 yr Clinical: June 21, 2005.
  17. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003;1:20.
  18. Data on file, Amgen. TEMPO CSR 57599 3 yr Radiographic. November 22, 2005.
  19. Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002;46:1443-1450.
  20. Data on file, Amgen; 1623 Final CSR: December 15, 2009.
  21. Genovese MC, Bathon JM, Fleischmann RM, et al. Long-term safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005;32:1232-1242.
  22. Data on file, Amgen; 1612 ERA 1 yr: July 6, 1999.
  23. Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-1593.

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.

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.