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.

In adult moderate to severe plaque psoriasis (PsO) and psoriatic arthritis (PsA)

In adult moderate to severe plaque psoriasis (PsO) and psoriatic arthritis (PsA)

For short-term and long-term results,

Take the next step with ENBREL

ENBREL has been proven to work for adults with chronic moderate to severe plaque PsO who are candidates for systemic therapy or phototherapy.1 ENBREL has also been proven to work for psoriatic arthritis.2

Navigating chronic moderate to severe plaque PsO is a lifelong journey


Typical plaque psoriasis patients may have a disease duration of more than 30 years3


  • Psoriasis affects 2%-4% of the US population, with ~1/3 of adult cases beginning during childhood4,5

Efficacy of ENBREL was evaluated at Week 12 and through 120 weeks2,6

ENBREL Global Psoriasis Pivotal Trial

  • The ENBREL Global Psoriasis Pivotal Trial was a multicenter, double-blind, randomized, phase 3 trial of 611 adult patients with active but clinically stable plaque PsO involving at least 10% of body surface area (BSA) and a minimum PASI score of 10. However, 583 patients received at least one dose of study drug and were included in the primary analysis. Patients received ENBREL 50 mg, 25 mg, or placebo twice weekly (BIW) over 12 weeks. After 12 weeks, all patients received open-label ENBREL 25 mg BIW. Patients were limited to low- to moderate strength topical corticosteroids in the axillary, groin, and scalp regions.1
  • Primary endpoint: 46% of patients achieved PASI 75 at week 12 in the ENBREL 50 mg BIW group (n=203) vs. 3% with placebo (n=204)2
  • Select secondary endpoints: Percent improvement from baseline PASI at Weeks 12, 24, and 487
  • A post hoc analysis was conducted for the OLE, a singular study comprised of patients from 2 parent trials, the Global Psoriasis Pivotal Trial and the US Psoriasis Pivotal Trial. Patients from the Global Psoriasis Pivotal Trial had the option to enroll in the OLE after completing a minimum of 36 weeks 7,8,9
  • OLE primary endpoints: The incidence of adverse events, infectious episodes, serious adverse events, serious infectious episodes, injection site reactions, changes from baseline in laboratory values, and presence/absence of an antibody response8
  • OLE select secondary endpoints: Percent improvement from baseline of the parent study PASI, at Weeks 12, 24, and 488
View full study design

ENBREL efficacy at Week 12 (primary and select secondary endpoints)2

  • Nearly half (46%) of patients saw 75% skin clearance in their moderate to severe plaque PsO in 12 weeks with ENBREL in the 50 mg BIW group (n=203) vs 3% with placebo (n=204) (primary endpoint; ITT NRI analysis)2
  • 66% mean PASI improvement at Week 12 in the ENBREL 50 mg BIW group (n=194) vs 0.1% with placebo (n=193) (mITT LOCF analysis)10

ENBREL efficacy through 120 weeks1,6

  • Open-label extension (OLE) results are from post hoc analysis. These results are exploratory and no statistical conclusions can be drawn
  • Consider OLE study limitations when interpreting results. The open-label extension is not blinded, not controlled, and includes inherent self-selection bias. A total of 20 patients (2.2%) had adverse events that led to discontinuation of the study8

ENBREL has an established safety profile.

Learn about long-term safety data for Enbrel

ENBREL provides results you can see

Actual photos of patients from the ENBREL Global Psoriasis Pivotal Trial13

  • These photos depict only a select area of the patient’s skin involvement. Included below the photos are the patients’ actual PASI scores at baseline, Week 12, and Week 24

Patients experienced less itch and skin pain with ENBREL

ENBREL Phase 3 Study

  • The ENBREL Phase 3 Study was a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of ENBREL 50 mg BIW vs placebo.14 Patients were ≥18 years old with active and clinically significant plaque psoriasis involving ≥10% BSA and a minimum PASI score of 10 at screening14

Efficacy results at Week 12

Primary endpoint:

  • 47% of patients achieved PASI 75 with ENBREL (mean baseline PASI=18.3)14

Select secondary endpoints:

  • The severity of skin pain and itch was assessed by patients based on a single-item questionnaire rating it on a scale of 0 (none) to 5 (severe) for itch, and 0 (none) to 10 (severe) for pain14
  • Patient-reported outcomes of itching and improvement from baseline in skin pain at Week 12 were secondary endpoints14
View full study design

Patient-reported outcomes14

In chronic moderate to severe plaque psoriasis (PsO)2

ENBREL provides recapturable results2,9,15

ENBREL US Psoriasis Pivotal Trial

  • The US Psoriasis Pivotal Trial was a multicenter, double-blind, phase 3 study of patients with active but clinically stable plaque psoriasis involving at least 10% of body surface and a minimum PASI score of 10. Patients had previously received phototherapy or systemic psoriasis therapy at least once or had been a candidate for such therapy. Patients were limited to low-to moderate-strength topical corticosteroids in the axillary, groin, and scalp regions1,7
  • Primary endpoint:  49% of patients achieved a PASI 75 score by Week 12 in the ENBREL 50 mg BIW group (n=164; LOCF) vs. 4% with placebo (n=166)16
  • Secondary endpoints: PASI 50 and 90 achievement, percent improvement from baseline PASI, static global assessment of psoriasis clear or almost clear, and the patient’s global assessment of psoriasis at Weeks 12, 24, 48, and 729,16
  • A post hoc analysis was conducted for the OLE, a singular study comprised of patients from 2 parent trials. Patients from the US Psoriasis Pivotal trial had the option to enroll in the OLE after completing a minimum of 60 weeks7,8,9
  • OLE Primary endpoint: The incidence of adverse events, infectious episodes, serious adverse events, serious infectious episodes, injection site reactions, changes from baseline in laboratory values and presence/absence of an antibody response8
  • OLE Select Secondary endpoints: Percent PASI improvement relative to baseline in the parent study8
View full study design

ENBREL recaptured almost all of its initial response following suspension of treatment for up to 5 months among these responders.2,9,15


  • The US Psoriasis Pivotal Trial was designed to assess retreatment after withdrawal. Patients with ≥50% PASI improvement from baseline at Week 24 discontinued ENBREL treatment. Upon relapse (loss of ≥50% PASI improvement obtained before Week 24), patients resumed blinded ENBREL therapy at the dose they received from Weeks 13-249,16
  • The mean numerical difference for each patient (primary endpoint) between the PASI score at Week 12 of retreatment and the PASI score at Week 12 of initial treatment in the ENBREL 50 mg BIW group was -1.4 (±0.5) and in the ENBREL 25 mg BIW group was -0.3 (±0.5)9

ENBREL recaptured efficacy results for up to 132 weeks2,6,9,16


  • Open label extension results are from post hoc analysis. These results are exploratory and no statistical conclusions can be drawn.
  • Consider OLE study limitations when interpreting results. The open-label extension is not blinded, not controlled, and includes inherent self-selection bias. A total of 20 patients (2.2%) had adverse events that let to discontinuation of the study8

ENBREL provides demonstrated efficacy in patients with moderate to severe plaque psoriasis

ENBREL Global Psoriasis Pivotal Trial

  • The ENBREL Global Psoriasis Pivotal Trial was a multicenter, double-blind, randomized, phase 3 trial of 611 adult patients with active but clinically stable plaque PsO involving at least 10% of body surface area (BSA) and a minimum PASI score of 10. However, 583 patients received at least one dose of study drug and were included in the primary analysis. Patients received ENBREL 50 mg, 25 mg, or placebo BIW over 12 weeks. After 12 weeks, all patients received open-label ENBREL 25 mg BIW. Patients were limited to low- to moderate-strength topical corticosteroids in the axillary, groin, and scalp regions.1,7
  • Primary endpoint: 46% of patients achieved PASI 75 at week 12 in the ENBREL 50 mg BIW group (n=203) vs. 3% with placebo (n=204)2
  • Select secondary endpoints: Percent improvement from baseline PASI, PASI 50, PASI 90 of clear or almost clear at Weeks 12 and 24, PASI 75 at 24 weeks7

View full study design

PASI results

  • 69% mean PASI improvement at Week 12 in the ENBREL 50 mg BIW group (n=194) vs 0.1% with placebo (n=193) (mITT LOCF analysis)10‡*

PASI results in patients who failed apremilast18

PsO Apremilast Failure Trial

  • The PsO Apremilast Failure Trial was a multicenter, open-label, single-arm, phase 4 estimation study in 80 patients ≥18 years old with moderate to severe plaque PsO with BSA ≥10%, PASI ≥10, and sPGA ≥3 who had failed apremilast. Failed therapy with apremilast (at least 4 weeks of treatment) for chronic moderate to severe plaque PsO was defined as: (1) failure to achieve adequate clinical response in the opinion of the investigator, (2) loss of adequate clinical response in the opinion of the investigator, or (3) intolerability to apremilast in the opinion of the investigator. Patients were excluded from the study if they had used a biologic for PsO AND either did not have a satisfactory response (sPGA 0 or 1) OR had a clinically significant adverse event19
  • Primary endpoint: 42% of patients achieved PASI 75 with ENBREL at 12 weeks19
  • Select secondary endpoints: PASI 75 response at Week 24, PASI 50 and 90 response at Weeks 12 and 24, Psoriasis Symptom Inventory (PSI) total and component scores at Weeks 12 and 2419

View full study design

PASI Results

Open-label results from estimation study are exploratory in nature and no statistical conclusions can be drawn.


ENBREL Psoriasis Symptom Inventory (PSI) scores from apremilast failure study

PSI is a validated PsO-specific Patient Reported Outcomes (PRO) measure that reflects a patient’s perception of symptom severity for 8 key signs and symptoms: itch, redness, scaling, burning, stinging, cracking, flaking, pain. Patients use the PSI questionnaire to assess the severity of each symptom (not at all, mild, moderate, severe, or very severe). The healthcare professional then scores the severity of each symptom. Learn more about the PSI tool and how it is used.20,21


47% reduction in overall PSI score with ENBREL after failure with apremilast at Week 1218



All PSI signs and symptoms reduced by 40%-50% with ENBREL at Week 1218


Psoriasis Symptom Inventory (PSI) is a validated PsO-specific Patient Reported Outcomes (PRO) measure that reflects a patient's perception of symptom severity

PSI looks at 8 signs and symptoms key to assessing severity of PsO20,21


This PsO-specific PRO measure has met the recommendations of the FDA's PRO Guidance22


Use the PSI Tool with your patients who have moderate to severe plaque psoriasis

This PSI questionnaire allows patients to assess their non-observable symptoms at each appointment: itch, sensations of burning, stinging, and pain.20, 21, 23

Example of PSI Tool when filled out by patient

Healthcare professionals then score the severity of each symptom on a scale of 0 (not at all) to 4 (very severe) 20,21

In adult chronic moderate to severe plaque PsO

Many patients struggle with scalp involvement24,25

  • An estimated 1.2 million adults aged ≥20 in the US have moderate to severe PsO26
  • The scalp is often the first site of presentation25
  • In a questionnaire taken by 752 people, as many as 80% of people with plaque PsO may have scalp involvement24,25
  • For many patients, plaque PsO of the scalp is the most difficult aspect of their disease owing to the visibility of the lesions25

Plaque PsO involving the scalp remains a difficult-to-treat area of the body25

Photo is from a moderate to severe plaque psoriasis patient. Photos that depict scalp involvement do not represent the patient's complete skin involvement.

ENBREL offers proven efficacy from head to toe

ENBREL Global Psoriasis Pivotal Trial

  • The ENBREL Global Psoriasis Pivotal Trial was a multicenter, double-blind, randomized, phase 3 trial of 611 adult patients with active but clinically stable plaque PsO involving at least 10% of body surface area (BSA) and a minimum PASI score of 10. However, 583 patients received at least one dose of study drug and were included in the primary analysis. Patients received ENBREL 50 mg, 25 mg, or placebo BIW over 12 weeks. After 12 weeks, all patients received open-label ENBREL 25 mg BIW. Patients were limited to low- to moderate strength topical corticosteroids in the axillary, groin, and scalp regions.1
  • Primary endpoint: 46% of patients achieved PASI 75 at week 12 in the ENBREL 50 mg BIW group (n=203) vs. 3% with placebo (n=204)2
  • Secondary endpoints: Percent improvement from baseline PASI at Weeks 12, 24, and 487

View full study design

ENBREL demonstrated overall mean Psoriasis Scalp Severity Index (PSSI) and PASI improvements

ENBREL Scalp Involvement Study

  • The ENBREL Scalp Involvement Study was a multicenter, double-blind, randomized, placebo-controlled trial of 124 adult patients with active but clinically stable plaque PsO involving at least 10% of BSA and a minimum PASI score of 10. Patients were also required to have ≥30% involvement of the scalp surface area (SSA) and a minimum PSSI score of 15. Patients received ENBREL 50 mg or placebo BIW over 12 weeks. From Weeks 12 to 24, patients received ENBREL 50 mg BIW (if initially randomized to placebo) or ENBREL 50 mg QW (if initially randomized to ENBREL 50 mg BIW)27,28
  • Primary endpoint: 87% mean PSSI improvement in ENBREL patients vs 20% in patients taking placebo at Week 12 (LOCF)27
  • Select secondary endpoints: PSSI 75 at Week 12 and percent change in PSSI from Week 12 to Week 24 in subjects switching from placebo to ENBREL at Week 1227,28
  • Select exploratory endpoint: Mean percentage improvement in PASI from basline, PASI 50, PASI 75, PASI 90, PSSI 50, and PSSI 90 and the severity of itch and pain on the scalp at weeks 12-2427,28

View full study design

  • Among PSSI 75 achievers, the median time to PSSI 50 and PSSI 75 was approximately 4 weeks and approximately 8 weeks, respectively29

ENBREL provides scalp results you can see

Actual photos of patients from the ENBREL Scalp Involvement Study30

  • These are actual photos from ENBREL clinical trial patients and depict only a select area of the patients' scalp involvement. Included below the photos are the patients' actual PSSI scores at baseline, Week 12, and Week 24

Patients experienced less scalp itch with ENBREL

  • The severity of scalp itch was assessed by patients based on a single-item questionnaire** rating it on a scale of 0 (none) to 5 (severe)28,31
  • Scalp itch was assessed as an exploratory endpoint in this study and no statistical conclusions can be drawn28,31

Patients experienced less scalp pain with ENBREL

  • The severity of scalp pain was assessed by patients based on a single-item questionnaire‡‡ rating it on a scale of 0 (none) to 5 (severe)28,31
  • Scalp pain was assessed as an exploratory endpoint in this study and no statistical conclusions can be drawn28,31

For adult patients, step-down dosing is recommended.2

See dosing information

1 out of 3 plaque psoriasis (PsO) patients may develop PsA32


In PsA, joint damage is irreversible and can get worse over time33,34


Patients with skin symptoms may have underlying joint damage from PsA33,35

~7 out of 10 patients

have skin symptoms appear before joint pain and swelling36,37

~1 out of 2 PsA patients

have joint damage33,35

"PsA can be a very severe disease with significant functional impairment... Therefore, we strongly encourage dermatologists to actively seek signs and symptoms of PsA at every patient's visit."38

–American Academy of Dermatology (AAD) 2008 Psoriatic Arthritis Guidelines

The 2015 GRAPPA* guidelines strongly recommended TNF inhibitors as a first-line treatment option for patients with peripheral arthritis39


Stand up to PsA one step at a time with ENBREL

ENBREL Psoriatic Arthritis Pivotal Trial

  • The ENBREL Psoriatic Arthritis Pivotal Trial, a 2-year, multicenter, double-blind, phase 3 study of 205 patients with active PsA40,41
  • At Week 12, 59% (n=101) of patients on ENBREL achieved the primary clinical endpoint of an American College of Rheumatology (ACR) 20 response vs 15% (n=104) of patients on placebo (P<0.0001)40
  • The primary radiographic endpoint of mean change from baseline in Total Sharp Score (TSS) was -0.03 for ENBREL patients vs. 1.0 for placebo patients at Year 1 (P=0.0001)40,41
View full study design

ENBREL is radiographically proven to inhibit the progression of further joint damage2

Significant improvements in physical function with ENBREL


The majority of ENBREL patients achieved physical function consistent with the general population (HAQ score ≤0.5) at Week 2442,43†


  • At Week 24, 60% of patients on ENBREL (n=101) achieved a HAQ score ≤0.5 vs 29% of patients on placebo (n=104)42†

Patients felt less pain after treatment with ENBREL

 

  • Results were similar between ENBREL monotherapy and ENBREL + MTX in a post hoc analysis—patients on ENBREL monotherapy (n=57) experienced a 42% decrease and patients on ENBREL + MTX (n=44) experienced a 50% decrease in pain at Week 2442
  • Post hoc analyses are exploratory and no statistical conclusions can be drawn

Patients achieved clearer skin with ENBREL41

  • 47% and 18% of patients achieved PASI 50 at Week 24 in the ENBREL and placebo arms, respectively41§
  • 23% and 3% of patients achieved PASI 75 at Week 24 in the ENBREL and placebo arms, respectively41§
  • 54% and 23% of patients had static Physician's Global Assessment (sPGA) of clear or almost clear at Week 24 in the ENBREL and placebo arms, respectively41¶

In a post hoc analysis of the PsA Pivotal Study


  • Material Limitations: At baseline, 20% of patients in both arms had an sPGA of almost clear. These data are based on a post hoc analysis, and therefore the study was not designed to demonstrate definitive rates of clear or almost clear sPGA among the patients in this subgroup. No statistical conclusions can be drawn from this analysis41

An estimated 68% of patients with PsA have ≤3% BSA involvement (based on data from the CORRONA Registry; N=1,688)45


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. 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.
  2. Enbrel® (etanercept) Prescribing Information, lmmunex Corporation, Thousand Oaks, Calif.
  3. Nijsten T, Margolis DJ, Feldman SR, Rolstad T, Stern RS. Traditional systemic treatments have not fully met the needs of psoriasis patients: results from a national survey. J Am Acad Dermatol. 2005;52:434-444.
  4. Bronckers IM, Paller AS, van Geel MJ, van de Kerkhof PC, Seyger MM. Psoriasis in children and adolescents: diagnosis, management and comorbidities. Pediatr Drugs. 2015;17:373-384.
  5. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
  6. Data on file, Amgen; 115 Subanalysis: December 21, 2009.
  7. Data on file, Amgen; CSR 1642: October 8, 2003.
  8. Data on file, Amgen; 115 CSR: November 28, 2005.
  9. Data on file, Amgen; CSR 1639: October 8, 2003.
  10. Data on file, Amgen. 1642 Subanalysis. May 31, 2007.
  11. Elewski B, Leonardi C, Gottlieb A, et al. Sustained long-term clinical efficacy and safety for up to 2.5 years of etanercept in patients with psoriasis. Poster presented at: 64th Annual Meeting of the American Academy of Dermatology; March 3-7, 2006; San Francisco, CA.
  12. Data on file, Amgen; Biostats Memo Long-term Efficacy Up To 144 Weeks: October 18, 2011.
  13. Data on file, Amgen; 1642 Patient PASI Data: May 25, 2007.
  14. Data on file, Amgen; CSR 20030117 Week 12 Readout. June 17, 2004.
  15. Gordon KB, Gottlieb AB, Leonardi CL, et al. Clinical response in psoriasis patients discontinued from and then reinitiated on etanercept therapy. J Dermatolog Treat. 2006;17:9-17.
  16. 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.
  17. Data on file, Amgen; 20021642 PASI Components Memo: February 28, 2014.
  18. Data on file, Amgen; Summary of Results February 19, 2018. Amgen protocol number 20150252.
  19. Data on file, Amgen; CSR 20150252: February 5, 2016.
  20. Martin ML, McCarrier KP, Chiou CF, et al. Early development and qualitative evidence of content validity for the Psoriasis Symptom Inventory (PS), a patient-reported outcome measure of psoriasis symptom severity. J Dermatolog Treat. 2013: 24:255-260.
  21. Bushnell DM, Martin ML, McCarrier KP, et al. Validation of the Psoriasis Symptom Inventory (PSI), a patient-reported outcome measure to assess psoriasis symptom severity. J Dermatolog Treat. 2013;24:356-360.
  22. Cheng R. A review of patient reported outcomes (PROs) in psoriasis according to the Food and Drug Administration (FDA) PRO guidance criteria. Presented at: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 17th Annual European Congress; November 8-12, 2014; Amsterdam, Netherlands.
  23. Expanding our understanding of meaningful change from a patient perspective. Presented at: Seventh Annual Patient-Reported Outcome (PRO) Consortium Workshop; April 27-28, 2016; Silver Spring, MD.
  24. van de Kerkhof PCM, Steegers-Theunissen RPM, Kuipers MV. Evaluation of topical drug treatment in psoriasis. Dermatology. 1998;197:31-36.
  25. Papp K, Berth-Jones J, Kragballe K, Wozel G, de la Brassinne M. Scalp psoriasis: a review of current topical treatment options. J Eur Acad Dermatol Venereol. 2007;21:1151-1160.
  26. Helmick CG, Lee-Han H, Hirsch SC, Baird TL, Bartlett CL. Prevalence of psoriasis among adults in the US: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47:37-45.
  27. Bagel J, Lynde C, Tyring S, Kricorian G, Shi Y, Klekotka P. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. J Am Acad Dermatol. 2012;67:86-92.
  28. Data on file, Amgen; CSR20080014: July 22, 2010.
  29. Data on file: Biostats Memorandum Psoriasis Flares in Pivotal Studies. May 2016.
  30. Data on file: CSR 20080014 Scalp Photos July 22, 2010.
  31. Data on file, Amgen; CSR 20170516 Scalp pain and itching PRO memo: August 13, 2017.
  32. National Psoriasis Foundation Website. About psoriatic arthritis. https://www.psoriasis.org/about-psoriatic-arthritis. Accessed March 13, 2018.
  33. Kane D, Stafford L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology. 2003;42:1460-1480.
  34. McArdle A, Pennington S, FitzGerald O. Clinical features of psoriatic arthritis: a comprehensive review of unmet clinical needs. Clin Rev Allerg Immunol. 2017:1-24.
  35. Torre Alonso JC, Rodriguez PA, Castrillo JM, et al. Psoriatic arthritis (PA): a clinical, immunological and radiological study of 180 patients. Br J Rheumatol. 1991;30:245-250.
  36. Mease PJ. Cytokine blockers in psoriatic arthritis. Ann Rheum Dis. 2001;60(suppl 3):iii37-iii40.
  37. Mease PJ, Goffe BS. Diagnosis and treatment of psoriatic arthritis. J Am Acad Dermatol. 2005;52:1-19.
  38. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58:851-864.
  39. Coates LC, Kavanaugh A, Mease PJ, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis Rheum. 2016;68:1060-1071.
  40. Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50:2264-2272.
  41. Data on file, Amgen; 1630 PsA 2 yr: August 5, 2004.
  42. Data on file, Amgen; Outcomes for study 160030 PsA ETN monotherapy: May 10, 2016.
  43. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003;1:20.
  44. Data on file, Amgen; PsA Study BSA sPGA: March 22, 2017.
  45. Data on file, Amgen; CORRONA Report: September 11, 2017.

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.