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

Take the next step with ENBREL

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.1

ENBREL provides consistent results across body regions

ENBREL Global Psoriasis Pivotal Trial

  • The ENBREL Global Psoriasis Pivotal Trial was a 24-week, randomized, multicenter, double-blind, placebo-controlled, phase 3 study that included 611 adult patients with active but clinically stable moderate to severe plaque PsO. Patients were randomized to receive ENBREL 50 mg, ENBREL 25 mg, or placebo administered BIW over 12 weeks, followed by open-label ENBREL 25 mg BIW for an additional 12 weeks2
  • Primary Endpoint:  Nearly half (46%) of patients saw 75% skin clearance in their moderate to severe plaque PsO in 12 weeks with ENBREL* (n=203) vs. 3% with placebo (n=204) (ITT NRI analysis)1,3
  • Select secondary endpoints: Percent improvement from baseline PASI, PASI 50, PASI 90, sPGA of clear or almost clear at Weeks 12 and 24, PASI 75 at 24 weeks

View full study design

Mean % PASI improvement through 24 weeks from the Global Psoriasis Pivotal Trial (50 mg BIW/50 mg QW)4द
Mean % PASI improvement through 24 weeks from the Global Psoriasis Pivotal Trial
Mean % PASI improvement
through 24 weeks from the
Global Psoriasis Pivotal Trial
(50 mg BIW/50 mg QW)4द
Mean % PASI improvement through 24 weeks from the Global Psoriasis Pivotal Trial
Mean PASI improvement by region4द
Mean PASI improvement by region in week 12 and week 24
Mean PASI improvement by region4द
Mean PASI improvement by region in week 12 and week 24

*50 mg BIW.
sPGA=static Physician's Global Assessment.
Rates as observed with no imputation for missing data.4
§Post hoc analysis of the ENBREL Global Psoriasis Pivotal Trial. All patients who received at least one dose of investigational product were included. Patients received ENBREL 50 mg BIW for 12 weeks followed by ENBREL 50 mg QW through Week 24 (as observed).4
The efficacy and use of ENBREL are based on involvement across the entire BSA and not from individual body regions.1

Reinitiate ENBREL for recapturable results

ENBREL US Psoriasis Pivotal Trial

  • The ENBREL US Psoriasis Pivotal Trial was designed to assess retreatment after withdrawal. Patients with ≥50% PASI improvement from baseline at Week 24 (responders) 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 to 245-7
  • 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)6
  • 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)5
  • 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.

View full study design

Improvement in mean PASI in the US Psoriasis Pivotal Trial1,6||
Mean PASI improvement in the US Psoriasis Pivotal Trial
Improvement in mean PASI in the US Psoriasis Pivotal Trial1,6||
Mean PASI improvement in the US Psoriasis Pivotal Trial

||Patients included in this trial started with placebo, ENBREL 25 mg QW, ENBREL 25 mg BIW, or ENBREL 50 mg BIW for 12 weeks. After 12 weeks, placebo patients were switched to ENBREL 25 mg BIW.
**Patients who completed 12 weeks of retreatment.7
††Only patients with ≥50% PASI improvement from baseline at Week 24 discontinued ENBREL treatment and were enrolled in this part of the study.7
‡‡Last observation carried forward (LOCF).
§§As observed.

In adult chronic moderate to severe plaque PsO

Many patients struggle with scalp involvement8,9

  • An estimated 1.2 million adults aged ≥20 in the US have moderate to severe PsO10
  • The scalp is often the first site of presentation9
  • In a questionnaire taken by 752 people, as many as 80% of people with plaque PsO may have scalp involvement8,9
  • For many patients, plaque PsO of the scalp is the most difficult aspect of their disease owing to the visibility of the lesions9

Plaque PsO involving the scalp remains a difficult-to-treat area of the body9

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 results from head to toe

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)11,12
  • Primary Endpoint: 87% mean PSSI improvement in ENBREL patients vs 20% in patients taking placebo at Week 12 (LOCF)11
  • 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 1214,15
  • Select exploratory endpoints: Mean percentage improvement in PASI from baseline, PASI 50, PASI 75, PASI 90, PSSI 50, and PSSI 90 at 12 and 24 weeks, and the severity of itch and pain on the scalp14,15

View full study design

Mean percent improvement in PSSI score at Weeks 12 and 24 in the ENBREL Scalp Involvement Study11*
Mean percent improvement in PSSI score at Weeks 12 and 24 in the ENBREL Scalp Involvement Study11*

*ITT analysis with LOCF imputation.
P<0.0001 vs placebo.

  • Among PSSI 75 achievers, the median time to PSSI 50 and PSSI 75 was approximately 4 weeks and approximately 8 weeks, respectively13

ENBREL provides scalp results you can see

Actual photos of patients from the ENBREL Scalp Involvement Study14

  • 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
 
Baseline
 
Week 12 Results
 
Week 24 Results
 
Patient 1
Baseline
PSSI=42
Week 12 Results
PSSI=20 (52% improvement in PSSI)
Week 24 Results
PSSI=0 (100% improvement in PSSI)
Patient 2
Baseline
PSSI=27
Week 12 Results
PSSI=8 (70% improvement in PSSI)
Week 24 Results
PSSI=4 (85% improvement in PSSI)

Extensive skin involvement in moderate to severe plaque psoriasis often includes many areas of the body. ENBREL does not treat individual problem areas and efficacy benefits are a result of overall PASI improvements. These are actual photos from ENBREL clinical trial patients that reflect approximately 75% PSSI improvements in the areas shown. Mean PSSI improvement scores were determined by evaluating overall improvement in the entire head/scalp. These photos have not been retouched. Individual results may vary.1

ENBREL demonstrated overall mean PASI improvements

Mean percent improvement in PASI score at Weeks 12 and 24 in the ENBREL Scalp Involvement Study11,12‡
Mean percent improvement in PASI score at Weeks 12 and 24 in the ENBREL Scalp Involvement Study11,12‡

ITT analysis with LOCF imputation

ENBREL provides overall results you can see

Actual photos of patients from the ENBREL Scalp Involvement Study14

  • These photos depict only a select area of the patients’ skin involvement. Included below the photos are the patients’ actual PASI scores at baseline, Week 12, and Week 24
 
Baseline
 
Week 12 Results
 
Week 24 Results
 
Patient 1
Baseline
PASI=12.6
Week 12 Results
PASI=5.5 (56% improvement in PASI)
Week 24 Results
PASI=4 (68% improvement in PASI)
Patient 2
Baseline
PASI=25.9
Week 12 Results
PASI=8.8 (66% improvement in PASI)
Week 24 Results
PASI=3.8 (85% improvement in PASI)

Extensive skin involvement in moderate to severe plaque psoriasis often includes many areas of the body. ENBREL does not treat individual problem areas and efficacy benefits are a result of overall PASI improvements. Actual photos from ENBREL clinical trial patients that reflect approximately 75% PASI improvements in the areas shown. These photos have not been retouched. Individual results may vary.1

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)12,15
  • Scalp itch was assessed as an exploratory endpoint in this study and no statistical conclusions can be drawn15
Improvement in mean itch score through Week 2412,15§**
Improvement in mean itch score through Week 2412,15§**

§ Subjects were asked to rate their scalp itch as a component of a psoriasis clinical trial, so it can be reasonably assumed that the subjects answered this question attributing the scalp itch to their moderate to severe plaque psoriasis.

**ITT analysis with LOCF imputation.

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 10 (severe)12,15
  • Scalp pain was assessed as an exploratory endpoint in this study and no statistical conclusions can be drawn15
Improvement in mean pain score through Week 2412,15††‡‡
Improvement in mean pain score through Week 2412,15††‡‡

†† Subjects were asked to rate their scalp pain as a component of a psoriasis clinical trial, so it can be reasonably assumed that the subjects answered this question attributing the scalp pain to their moderate to severe plaque psoriasis.

‡‡ITT analysis with LOCF imputation.

1 out of 3 plaque psoriasis (PsO) patients may develop PsA16

 
In PsA, joint damage is irreversible and can get worse over time17,18
 

Patients with skin symptoms may have underlying joint damage from PsA17,19

~7 out of 10 patients have skin symptoms appear
before joint pain and swelling20,21



~1 out of 2 PsA patients have joint damage17,19

“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.”22

–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 arthritis23
 

*GRAPPA=Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

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 PsA24,25
  • At Week 12, 59% (n=101) of patients on ENBREL achieved the primary clinical endpoint of an ACR 20 response vs 15% (n=104) of patients on placebo (P<0.0001)25
  • 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)24,25

View full study design

ENBREL is radiographically proven to inhibit the progression of further joint damage1

Mean change in Total Sharp Score (TSS)24
Mean change in
Total Sharp Score (TSS)24

Significant improvements in physical function with ENBREL

  • At Week 24, 60% of patients on ENBREL (n=101) achieved a HAQ score ≤0.5 vs 29% of patients on placebo (n=104)26†
 
The majority of ENBREL patients achieved physical function consistent with the general population (HAQ score ≤0.5) at Week 2426,27†
 

HAQ score of ≤0.5 is consistent with the score of the general population.27

Patients achieved clearer skin with ENBREL24

  • 47% and 18% of patients achieved PASI 50 at Week 24 in the ENBREL and placebo arms, respectively24‡
  • 23% and 3% of patients achieved PASI 75 at Week 24 in the ENBREL and placebo arms, respectively24‡
  • 54% and 23% of patients had sPGA of clear or almost clear at Week 24 in the ENBREL and placebo arms, respectively24§
In a post hoc analysis of the PsA Pivotal Study
sPGA** of clear or almost clear at Week 24 in patients with BSA ≥1% and <3% at baseline28§
sPGA** of clear or almost clear
at Week 24 in patients with
BSA ≥1% and <3% at baseline28§
  • 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 analysis24

View full study design

 
An estimated 68% of patients with PsA have ≤3% BSA involvement
(based on data from the CORRONA‡‡ Registry; N=1,688)29
 

Patients had plaque PsO involvement ≥3% BSA at baseline.
§Assessment was determined on a 0 to 5 (clear to severe PsO) scale.
**sPGA=static Physician’s Global Assessment.
††BSA=Body Surface Area
‡‡CORRONA=Consortium of Rheumatology Researchers of North America.

Patients felt less pain after treatment with ENBREL

Change in patient pain assessment24
Change in patient pain assessment24
  • 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 2426
  • Post hoc analyses are exploratory and no statistical conclusions can be drawn

Start with an established safety profile

The safety profile of ENBREL has been evaluated in 7 PsO trials, which included 4,410 patients, and the PsA pivotal trial, which included 205 patients.24,30

View the safety profile

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. Data on file, Amgen; 1642 Subanalysis: May 31, 2007.
  4. Data on file, Amgen; 20021642 PASI Components Memo: February 28, 2014.
  5. 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.
  6. Data on file, Amgen; CSR1639: October 8, 2003.
  7. 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.
  8. van de Kerkhof PCM, Steegers-Theunissen RPM, Kuipers MV. Evaluation of topical drug treatment in psoriasis. Dermatology. 1998;197:31-36.
  9. 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.
  10. 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.
  11. 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.
  12. Data on file, Amgen; CSR20080014: July 22, 2010.
  13. Data on file, Amgen; Biostats Memorandum Psoriasis Flares in Pivotal Studies: May 11, 2016.
  14. Data on file, Amgen; 20080014 PSSI and PASI Scores Memo: February 23, 2016.
  15. Data on file, Amgen; CSR 20170516 Scalp pain and itching PRO memo: August 13, 2017.
  16. National Psoriasis Foundation Web site. About psoriatic arthritis. https://www.psoriasis.org/about-psoriatic-arthritis. Accessed October 10, 2017.
  17. 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.
  18. 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.
  19. 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.
  20. Mease PJ. Cytokine blockers in psoriatic arthritis. Ann Rheum Dis. 2001;60(suppl 3):iii37-iii40.
  21. Mease P, Goffe BS. Diagnosis and treatment of psoriatic arthritis. J Am Acad Dermatol. 2005;52:1-19.
  22. 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.
  23. 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.
  24. Data on file, Amgen; 1630 PsA 2 yr: August 5, 2004.
  25. 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.
  26. Data on file, Amgen; Outcomes for study 160030 PsA ETN monotherapy: May 10, 2016.
  27. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003;1:20.
  28. Data on file, Amgen; PsA Study BSA sPGA: March 22, 2017.
  29. Data on file, Amgen; CORRONA Report: September 11, 2017.
  30. 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.
Prescription Enbrel® (etanercept) is administered by injection.
IMPORTANT SAFETY INFORMATION AND INDICATIONS
SERIOUS INFECTIONS

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

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

MALIGNANCIES

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

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

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

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

Pediatric Patients

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

NEUROLOGIC REACTIONS

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

CONGESTIVE HEART FAILURE

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

HEMATOLOGIC REACTIONS

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

HEPATITIS B REACTIVATION

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

ALLERGIC REACTIONS

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

IMMUNIZATIONS

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

AUTOIMMUNITY

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

WEGENER’S GRANULOMATOSIS PATIENTS

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

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

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

ADVERSE REACTIONS

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

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

DRUG INTERACTIONS

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

Please see Prescribing Information and Medication Guide.

INDICATIONS

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

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

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

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

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

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IMPORTANT SAFETY INFORMATION AND INDICATIONS: SERIOUS INFECTIONS

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

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

MALIGNANCIES

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

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

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

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

Pediatric Patients

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

NEUROLOGIC REACTIONS

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

CONGESTIVE HEART FAILURE

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

HEMATOLOGIC REACTIONS

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

HEPATITIS B REACTIVATION

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

ALLERGIC REACTIONS

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

IMMUNIZATIONS

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

AUTOIMMUNITY

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

WEGENER’S GRANULOMATOSIS PATIENTS

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

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

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

ADVERSE REACTIONS

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

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

DRUG INTERACTIONS

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

Please see Prescribing Information and Medication Guide.

INDICATIONS

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

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

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

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

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

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

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

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

MALIGNANCIES

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

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

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

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

Pediatric Patients

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

NEUROLOGIC REACTIONS

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

CONGESTIVE HEART FAILURE

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

HEMATOLOGIC REACTIONS

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

HEPATITIS B REACTIVATION

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

ALLERGIC REACTIONS

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

IMMUNIZATIONS

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

AUTOIMMUNITY

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

WEGENER’S GRANULOMATOSIS PATIENTS

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

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

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

ADVERSE REACTIONS

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

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

DRUG INTERACTIONS

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

Please see Prescribing Information and Medication Guide.

INDICATIONS

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

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

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

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

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