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.

ENBREL has a well-established safety profile


The safety profile of ENBREL in dermatology has been evaluated in many clinical studies in adult and pediatric patients.1

ENBREL select safety results in adult moderate to severe plaque PsO patients

The safety of ENBREL was evaluated in the ENBREL Global Psoriasis Pivotal Trial and the ENBREL US Psoriasis Pivotal Trial. The trials were multicenter, double-blind, phase 3 studies of patients with active but clinically stable plaque psoriasis.2,3

See Risks in Plaque Psoriasis and Psoriatic Arthritis Patients below

View full study design

Serious adverse event rates were similar to control1,4

Important Information about the Risks of Malignancies and Serious Infections

  • Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including ENBREL1
  • Lymphoma: In clinical trials of all TNF inhibitors, 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 inhibitors in the development of malignancies is unknown1,5,6
  • NMSC: Nonmelanoma skin cancer has been reported in patients treated with TNF antagonists including ENBREL. Among adult psoriasis patients treated with ENBREL (n=1,245) in controlled clinical trials, the observed rate of NMSC was 0.04 events/pt-yr vs 0.01 events/pt-yr among control-treated patients (n=720)1
  • Other malignancies: Other malignancies have been reported during postmarketing for ENBREL and other TNF blockers, including cases of acute and chronic leukemia1
  • Serious infection: Infections, including serious infections, some fatal, have been observed in patients treated with ENBREL. Discontinue ENBREL if a patient develops a serious infection or sepsis. Patients are at increased risk for developing serious infections when taking ENBREL that may lead to hospitalization or death. Most patients who developed these serious infections were taking concomitant immunosuppressants1
  • Opportunistic infection: In patients receiving TNF-blocking agents, opportunistic infections, including tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis, have been reported1
  • Tuberculosis: Cases of reactivation of TB or new TB infections have been observed in patients receiving ENBREL. Patients should be evaluated for TB risk factors and be tested for latent TB infection prior to initiating ENBREL and during treatment1

Consistent safety rates demonstrated through 3 years of continuous exposure in an integrated safety analysis7

An integrated safety analysis from 7 PsO trials evaluated the safety of ENBREL in over 4,400 patients.7 Data were combined from 4 double-blind, placebo-controlled trials and 3 open-label trials.7 Patients included in this analysis were ≥18 years of age with moderate to severe plaque psoriasis and had ≥10% BSA involvement at baseline.7

  • 1,965 patients were included in the short-term, placebo-controlled, double-blinded analysis (12 weeks) for a total of 283 patient-years of ENBREL exposure among 1,245 patients7‡
  • 4,410 patients were included in the long-term analysis (up to 144 weeks) for a total of 4,775 patient-years of ENBREL exposure7§¶

Objective

  • To determine the safety risk of short- and long-term ENBREL exposure in patients with plaque psoriasis7

Safety endpoints

  • Exposure-adjusted incidence rates** and standardized incidence ratio†† were calculated for malignancies, infectious adverse events, noninfectious adverse events, and clinically significant events7
  • Other adverse events of medical interest included lymphoma, tuberculosis, opportunistic infections, demyelination, and congestive heart failure7

Malignancy rates across these 7 PsO trials were comparable to the general population (SIR: 1.15; 95% CI: 0.78, 1.64)7††

These data come from 7 controlled and uncontrolled psoriasis studies.7 Safety data include patients who received continuous ENBREL 50 mg BIW therapy.7 Malignancy rates above do not include nonmelanoma skin cancers and in situ cancers other than bladder cancer.7 Cases of nonmelanoma skin cancer have been reported in clinical trials and postmarketing experience.1 Opportunistic infection rates do not include tuberculosis.1

  • These post hoc analysis results are exploratory and no statistical conclusions can be drawn
  • The most commonly reported adverse events in clinical trials were injection site reaction and infection1
  • Events/patient-year: A rate of 0.007 events/patient-year is equivalent to observing 0.7 malignancies among 100 patients taking study drug continuously for 1 year7

Other serious adverse events from the 7 studies:

  • 2 cases of demyelination were observed (0.0004 events/pt-yr)4,7
  • 7 cases of congestive heart failure were observed (0.001 events/pt-yr)4,7
  • 11 cases of myocardial infarction were observed (0.002 events/pt-yr)7

ENBREL has an established long-term safety profile

Real-world safety of ENBREL was analyzed in a 5-year observational registry (OBSERVE-5). OBSERVE-5 was a prospective, multicenter, observational surveillance registry evaluating data on long-term safety of ENBREL use in moderate to severe plaque psoriasis.17

View full study design

≥80% of enrolled patients continued their treatment with ENBREL at each time point.17

Adverse events of medical interest in OBSERVE-5

  • Events/patient-year: A serious adverse event rate of 0.0581 events/patient-year is equivalent to observing 5.81 serious adverse events among 100 patients taking study drug continuously for 1 year17

Select adverse events of medical interest across 6,167 patient-years of exposure18§§§:

  • No cases of opportunistic infections18
  • No cases of histoplasmosis18
  • No cases of coccidioidomycosis18
  • 2 cases of tuberculosis18
  • 2 cases of lymphoma18

Types of adverse events and reactions reported in pediatric patients with chronic moderate to severe plaque PsO

The safety of ENBREL was evaluated in the ENBREL Pediatric Psoriasis Pivotal Study, a 48-week randomized, double-blind, placebo-controlled US and Canadian study (parent study) in 211 patients with moderate to severe plaque PsO between 4 and 17 years of age. The 48-week parent study was followed up by a long-term, 264 week (5-year; n=182) open-label extension.1,24

View full study design

 

  • No serious adverse event was reported during the 12-week double-blind period25†
  • 1 subject withdrew from the study during the 12-week double-blind period due to an adverse event25

Adverse reaction profile was generally similar to adult PsO

  • In the 48-week clinical study in 211 children aged 4 to 17 years with pediatric PsO, the adverse reactions reported were similar to those seen in previous studies in adults with PsO1
  • In controlled trials, 7% of pediatric patients treated with ENBREL developed injection site reactions during the first 3 months of treatment1

IMPORTANT SAFETY CONSIDERATIONS

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.1

Long-term safety was consistent through 6 years of combined parent and open-label extension studies24

  • Long-term safety profile for up to 264 additional weeks was assessed in an open-label extension study and no new safety signals were identified1

  • No cases of malignancy, lymphoma, or opportunistic infection were reported among patients treated with ENBREL in the study24,27‡
  • 2 cases of serious infection among 181 pediatric patients treated with ENBREL24,27‡
    • Cellulitis (treatment related)
    • Infectious mononucleosis
  • Other serious adverse events included the following: abortion induced, anxiety, intestinal obstruction, osteonecrosis, and thyroid cyst24

ENBREL select safety results in psoriatic arthritis (PsA)

The safety of ENBREL was evaluated in the ENBREL Psoriatic Arthritis Pivotal Study, a 2-year, multicenter, double-blind, phase 3 study of 205 patients with active PsA.28

View full study design

 

  • During the controlled portion of the study, injection site reactions were reported in 36% of ENBREL subjects compared with 9% of placebo subjects (P<0.0001)28,29

View full study design

Important Information about the Risks of Malignancies and Serious Infections

  • Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including ENBREL1
  • Lymphoma: In clinical trials of all TNF inhibitors, 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 inhibitors in the development of malignancies is unknown1,5,6
  • NMSC: Nonmelanoma skin cancer has been reported in patients treated with TNF antagonists including ENBREL. Among adult psoriasis patients treated with ENBREL (n=1,245) in controlled clinical trials, the observed rate of NMSC was 0.04 events/pt-yr vs 0.01 events/pt-yr among control-treated patients (n=720)1
  • Other malignancies: Other malignancies have been reported during postmarketing for ENBREL and other TNF blockers, including cases of acute and chronic leukemia1
  • Serious infection: Infections, including serious infections, some fatal, have been observed in patients treated with ENBREL. Discontinue ENBREL if a patient develops a serious infection or sepsis. Patients are at increased risk for developing serious infections when taking ENBREL that may lead to hospitalization or death. Most patients who developed these serious infections were taking concomitant immunosuppressants1
  • Opportunistic infection: In patients receiving TNF-blocking agents, opportunistic infections, including tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis, have been reported1
  • Tuberculosis: Cases of reactivation of TB or new TB infections have been observed in patients receiving ENBREL. Patients should be evaluated for TB risk factors and be tested for latent TB infection prior to initiating ENBREL and during treatment1

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. Enbrel® (etanercept) Prescribing Information, lmmunex Corporation, Thousand Oaks, Calif.
  2. Papp KA, Tyring S, Lahfa M, et al; for the Etanercept Psoriasis Study Group. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol.2005;152:1304-1312.
  3. Leonardi CL, Powers JL, Matheson RT, et al; for the Etanercept Psoriasis Study Group. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349:2014-2022.
  4. Data on file: Safety Data Verification Memo. October 2013.
  5. US Food and Drug Administration website. Humira label and approval history. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed September 19, 2017.
  6. US Food and Drug Administration website. Remicade label and approval history. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed September 19, 2017.
  7. Pariser DM, Leonardi CL, Gordon K, et al. Integrated safety analysis: short- and long-term safety profiles of etanercept in patients with psoriasis. J Am Acad Dermatol. 2012;67:245-256.
  8. Data on file, Amgen; Year 1 Summary of Adverse Events: October 12, 2010.
  9. Data on file, Amgen; Year 2 Summary of Adverse Events: October 12, 2010.
  10. Data on file, Amgen; Year 3 Summary of Adverse Events: October 12, 2010.
  11. Data on file, Amgen; Exposure-adjusted Rate of OI: October 5, 2010.
  12. Last JM, ed. Spasoff RA, Harris SS, Thuriaux MC, assoc eds. A Dictionary of Epidemiology. 4th ed. New York, NY: Oxford University Press Inc.; 2001.
  13. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesda, MD: National Cancer Institute; 2012.
  14. Moreland LW, Weinblatt ME, Keystone EC, et al. Etanercept treatment in adults with established rheumatoid arthritis: 7 years of clinical experience. J Rheumatol. 2006;33:854-861.
  15. Stedman’s Medical Dictionary. 28th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005.
  16. Data on file, Amgen; Safety Information Amendment 103795: August 1, 2006.
  17. Kimball AB, Rothman KJ, Kricorian G, et al. OBSERVE-5: observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results. J Am Acad Dermatol. 2015;72:115-122.
  18. Data on file, Amgen; CSR 20040210: September 13, 2013.
  19. Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among US adults. N Engl J Med. 2015;373:415-427.
  20. Raff AB, Kroshinsky D. Cellulitis: a review. JAMA. 2016;316:325-337. 36.
  21. Yawn BP, Gilden D. The global epidemiology of herpes zoster. Neurology. 2013;81:928-930.
  22. NIH National Cancer Institute website. Cancer stat facts: Non-Hodgkin lymphoma. https://seer.cancer.gov/statfacts/html/nhl.html. Accessed September 18, 2017.
  23. NIH National Cancer Institute website. Cancer Stat Facts: Cancer of Any Site. https://seer. cancer.gov/statfacts/html/all.html. Accessed September 18, 2017.
  24. Paller AS, Siegfried EC, Pariser DM, et al. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol. 2016;74:280-287.
  25. Data on file, Amgen; CSR 20030211 Pediatric PsO double-blind: September 18, 2006.
  26. Data on file, Amgen; CSR 20050111 Serious adverse events: November 2, 2016.
  27. Data on file, Amgen; CSR 20050111 Pediatric PsO OLE: June 1, 2012.
  28. Data on file, Amgen; 1630 PsA 2 yr: October 2003.
  29. Data on file, Amgen; 1630 PsA 6 month: June 12, 2001.
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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 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.