INDICATIONS

ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with moderately to severely active rheumatoid arthritis. ENBREL can be taken with methotrexate or used alone. Read More

ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function...Read More

SEAM-PsA Study

Evaluation of ENBREL and MTX as monotherapies and as combination therapy in psoriatic arthritis (PsA)

SEAM-PsA Study

Evaluation of ENBREL and MTX as monotherapies and as combination therapy in psoriatic arthritis (PsA)

Study Design

The Study of Etanercept and Methotrexate (SEAM) PsA Study was a 48-week, multicenter, randomized, double-blind controlled study of 851 subjects with active PsA naïve to biologics and with no prior use of methotrexate (MTX) for the treatment of PsA. Eligible patients were randomized to receive ENBREL + MTX combination therapy (n=283), ENBREL monotherapy (n=284), or MTX monotherapy (n=284).1

Additional Study Details

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  • Primary endpoint: ACR 20 at Week 241
  • Select secondary endpoints: ACR 50 at Week 24, ACR 70 at Week 24, change in modified total Sharp score (mTSS), change in body surface area (BSA), percentage of patients achieving static Physician's Global Assessment (sPGA) of clear or almost clear, minimal disease activity (MDA) at Week 24, dactylitis improvement from baseline, enthesitis improvement from baseline, nail disease improvement from baseline1
  • At or after Week 24, subjects who had an inadequate response received rescue therapy with ENBREL plus MTX until the end of the treatment period. Inadequate response was defined as having <20% improvement in their tender joint count (TJC) and <20% in their swollen joint count (SJC) from baseline at or after Week 241
SEAM PsA Study SEAM PsA Study

a Rescue option = ENBREL 50 mg per week + MTX 20 mg per week if inadequate response (<20% improvement in TJC and SJC from baseline) at or after 24 weeks.1

Select Baseline Demographics/Characteristics1

Demographic/
Characteristics
MTX
Monotherapy
(n=284)
ENBREL
Monotherapy
(n=284)
ENBREL
+ MTX
(n=283)
Mean age in years (SD) 48.7
(13.1)
48.5
(13.5)
48.1
(12.7)
% female 56.3% 46.8% 49.1%
Mean years disease duration (SD) 3.6
(6.8)
3.1
(6.0)
3.0
(6.0)
Mean years mTSS (SD) 2.76
(0.12)
2.97
(0.13)
2.70
(0.12)
% dactylitis (LDI) 34.5% 33.8% 31.8%
% enthesitis (SPARCC) 67.3% 66.5% 69.3%
% nail disease (mNAPSI) 65.1% 72.5% 69.6%
Mean tender joint count (SD) 20.9
(15.0)
18.8
(14.5)
20.0
(15.3)
Mean swollen joint count (SD) 12.9
(9.9)
11.5
(9.6)
11.2
(9.1)
Mean % BSA 12.7% 10.8% 10.7%
Mean sPGA (SD) 2.6 (1.1) 2.6 (1.0) 2.5 (1.0)

LDI = Leeds Dactylitis Index; mNAPSI = modified Nail Psoriasis Severity Index; SD = standard deviation; SPARCC = Spondyloarthritis Research Consortium of Canada.

Selected Inclusion/Exclusion Criteria1,3

Inclusion criteria

  • Diagnosis of PsA by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria
  • ≥3 tender and ≥3 swollen joints (as part of a 66/68 joint count) at screening and at baseline
  • Active psoriatic skin lesion ≥2 cm in diameter
  • Naïve to etanercept and any other biologic for the treatment for PsA or psoriasis
  • No prior use of methotrexate for PsA (allowed if indicated for psoriasis as long as discontinuation was not due to toxicity or intolerance and treatment discontinued ≥6 months prior to initiation of etanercept)

Exclusion criteria

  • Prior or current use of cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent
  • Use of any of the following ≤3 months prior to screening: abatacept, anakinra, azathioprine, cyclosporine, gold, mycophenolate mofetil, prosorba column, tacrolimus, apremilast
  • Use of leflunomide ≤12 weeks prior to screening
  • Use of any of the following ≤4 weeks prior to screening: sulfasalazine; intraarticular, intramuscular, or intravenous corticosteroids, including adrenocorticotropic hormone; intraarticular hyaluronic acid injections; live vaccines

References:

  1. Mease PJ, Gladman DD, Collier DH, et al. Etanercept and methotrexate as monotherapy or in combination for psoriatic arthritis: primary results from a randomized, controlled phase III trial [published online ahead of print: February 12, 2019]. Arthritis Rheumatol. doi:10.1002/art.40851.

Joint Symptoms

Patients taking ENBREL with or without MTX experienced significant improvements in joint symptoms1
  • Primary endpoint: ACR 20 was achieved by 65% of patients with ENBREL + MTX and 61% of patients with ENBREL monotherapy vs 51% of patients with MTX at Week 241
Patients on ENBREL monotherapy and ENBREL + MTX experienced similar ACR 50 and ACR 70 responses at Week 24 Patients on ENBREL monotherapy and ENBREL + MTX experienced similar ACR 50 and ACR 70 responses at Week 24
  • These comparisons were not adjusted for multiplicity

Joint Damage

Patients on ENBREL with or without MTX did not experience progression of joint damage1,2
ENBREL inhibited the progression of joint damage with or without MTX ENBREL inhibited the progression of joint damage with or without MTX
  • These comparisons were not adjusted for multiplicity

Skin Symptoms

Patients on ENBREL monotherapy experienced improvements in sPGA1
8 out of 10 patients on ENBREL achieved sPGA of clear to almost clear at Week 24 8 out of 10 patients on ENBREL achieved sPGA of clear to almost clear at Week 24

These comparisons were not adjusted for multiplicity

  • Improvement in sPGA for patients with baseline BSA ≥3% with ENBREL + MTX was 78% at Week 241
  • Improvement in sPGA for patients with baseline BSA ≥10% with ENBREL + MTX was 79% at Week 241
~7 out of 10 patients on ENBREL achieved BSA improvement at Week 241
7 out of 10 patients on ENBREL achieved BSA improvement at Week 24 7 out of 10 patients on ENBREL achieved BSA improvement at Week 24

These comparisons were not adjusted for multiplicity.

  • Improvement in BSA for patients with baseline BSA ≥3% with ENBREL + MTX was 76% at Week 241,2
  • Improvement in BSA for patients with baseline BSA ≥10% with ENBREL + MTX was 82% at Week 241,2

Minimal Disease Activity

MDA measures the state of PsA disease activity and defines a target for treatment. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommends MDA as a potential treatment target, as it encompasses most aspects of the disease and there is no clear definition of remission.3-5

Patients With PsA Are Defined as Achieving MDA When They Meet 5 of the Following 7 Criteria3:

  • Tender joint count ≤1
  • Swollen joint count ≤1
  • PASI ≤1 or BSA ≤3%
  • Patient pain VAS ≤15
  • Patient global activity VAS ≤20
  • HAQ ≤0.5
  • Tender entheseal points ≤1

HAQ = Health Assessment Questionnaire; PASI = Psoriasis Area and Severity Index; VAS = visual analog scale.

Patients taking ENBREL with or without MTX experienced significant improvements in MDA response rates

MDA at 24 Weeks (Key Secondary Endpoint)1

MDA at 24 Weeks (Key Secondary Endpoint) MDA at 24 Weeks (Key Secondary Endpoint)

a P=0.005 vs MTX (adjusted).1,2

For ACR 20 and MDA at Week 24, formal comparisons were tested using Bonferroni-based gatekeeping chain procedure to control the type 1 error rate at 0.05 and nonresponder imputation was used for missing data. For other endpoints, P values are nominal (not adjusted for multiplicity) and data were analyzed as observed.1

Dactylitis and Enthesitis

Patients taking ENBREL with or without MTX experienced improvements in dactylitis and enthesitis1,6
Patients taking ENBREL with or without MTX experienced improvements in dactylitis and enthesitis Patients taking ENBREL with or without MTX experienced improvements in dactylitis and enthesitis
  • These comparisons were not adjusted for multiplicity

Nail Disease

Patients taking ENBREL with or without MTX experienced improvements in nail disease (mNAPSI)1,6
Patients taking ENBREL with or without MTX experienced improvements in nail disease(mNAPSI) Patients taking ENBREL with or without MTX experienced improvements in nail disease(mNAPSI)
  • These comparisons were not adjusted for multiplicity

PsA Pivotal Study

Evaluation of ENBREL in PsA, including joint, skin, and pain results

PsA Pivotal Study

Evaluation of ENBREL in PsA, including joint, skin, and pain results

 

Study Design

The PsA Pivotal Study was a 24-week, multicenter, double-blind study of 205 patients with active PsA who had a mean duration of arthritic disease of 9.1 years and mean duration of plaque psoriasis of 19 years (with a qualifying target skin lesion). Patients were randomized to receive ENBREL 25 mg biweekly (BIW, n=101) or placebo BIW (n=104). The 24-week, double-blind period was followed by a maintenance period of up to 24 weeks to allow all patients to complete the double-blind study. At Week 48, the maintenance period was followed by an open-label extension (OLE, n=168). Concomitant use of MTX, NSAID, corticosteroids, and topical therapies were permitted in the OLE at the discretion of the investigator.7

Additional Study Details

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  • Primary endpoints: ACR 20 at Week 12, change in mTSS at Year 11
  • Select secondary endpoints: PASI 75 at Week 24, sPGA of clear or almost clear at Week 121
PsA Pivotal Study PsA Pivotal Study

a Patients were stratified by MTX use at baseline for equal distribution between treatment arms. Patients on MTX therapy at enrollment (stable for 2 months) could continue at a stable dose of 25 mg/week MTX.2

b Stable use of corticosteroids and/or NSAIDs allowed.2

c 81 from placebo group; 87 from ENBREL group.1

References:

  1. Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheumatol. 2004;50:2264-2272.
  2. Data on file, Amgen; 1630 PsA 2 yr. August 5, 2004.

Primary Endpoints

  • ACR 20 was achieved by 59% of patients with ENBREL vs 15% with placebo at Week 12 of the double-blind period (P<0.001)7
  • Change from baseline in mTSS was -0.03 for ENBREL patients vs 1.0 for patients taking placebo at Year 1 (P=0.0001)7

Joint Damage

ENBREL significantly inhibited joint damage progression
  • Change from baseline in mTSS was -0.03 for ENBREL patients (n=101) vs 1.0 for patients taking placebo (n=104) at Year 1 (P=0.0001)7*
  • ENBREL inhibited the progression of bone erosion for patients taking ENBREL from the beginning of the study (mean change from baseline was -0.4 for the ENBREL arm vs 0.2 for the placebo arm at Year 2)8

* Per protocol, in order to compare the radiographic images at Year 2 with images from baseline, 6 months, and 1 year, all images were reread. Because of the known variability in evaluation of radiographic images in psoriatic arthritis, all radiographs were reread, blinded to patient and time point, by 2 of 4 physicians. Radiographic scores were reported as an average from the 2 readers. Thus, the Year 2 scoring of the radiographic images is considered a new reading of the Year 1 time point.

Mean Change in mTSS9,a

Mean Change in mTSS Mean Change in mTSS

a An mTSS, which included distal interphalangeal joints, was used. All radiographic data are based on the radiographic intent-to-treat (ITT) analysis, defined as all randomly assigned patients with acceptable baseline and post-baseline radiographs. Linear extrapolation methodology was used.

b Patients were stratified by concomitant MTX.

Skin Symptoms

ENBREL helps patients achieve clearer skin7,8
  • 47% and 18% of patients achieved PASI 50 at Week 24 in the ENBREL and placebo arms, respectively
  • 23% and 3% of patients achieved PASI 75 at Week 24 in the ENBREL and placebo arms, respectively
  • 54% and 23% of patients had an sPGA of clear or almost clear at Week 24 in the ENBREL and placebo arms, respectively

sPGA of Clear or Almost Clear at Week 24 in Patients With ≥1% and <3% BSA at Baseline10,a

sPGA of Clear or Almost Clear at Week 24 in Patients With Greater than or Equal to 1% and Less Than <3% BSA at Baseline sPGA of Clear or Almost Clear at Week 24 in Patients With Greater than or Equal to 1% and Less Than <3% BSA at Baseline

a Patients had plaque psoriasis involvement ≥3% BSA at baseline.8

b Patients were stratified by concomitant MTX.8

§ Assessment was determined on a 0 to 5 (clear to severe psoriasis) scale.8

Pain

ENBREL helps patients feel less pain (based on VAS)
  • Improvement in patient pain assessment for ENBREL patients vs patients taking placebo was 48% vs -1% at Week 12 and 46% vs -3%, respectively, at Week 24 (P<0.0001)8

Change in Patient Pain Assessment (VAS)8

Change in Patient Pain Assessment (VAS) Change in Patient Pain Assessment (VAS)

a Patients were stratified by concomitant MTX.

Physical Function

ENBREL improved patients’ physical function
  • Mean improvement in HAQ score for ENBREL patients vs patients taking placebo was 54% vs 6%, respectively, at Week 24 (P<0.001)11
  • At Week 24, patients on ENBREL monotherapy achieved a mean 53% improvement in HAQ score, and patients on ENBREL + MTX achieved a mean 55% improvement12

Patients With HAQ Score of ≤0.5 at Week 2412,a

Patients With HAQ Score of Less Than or Equal to 0.5% at Week 24 Patients With HAQ Score of Less Than or Equal to 0.5% at Week 24

a HAQ score of ≤0.5 is consistent with the score of the general population.13

b Patients were stratified by concomitant MTX.8

PSORIATIC ARTHRITIS

Learn more about PsA Safety Resultsfooter-cta-icon

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 (RA). ENBREL can be initiated in combination with methotrexate (MTX) or used alone.

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 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 in patients with active ankylosing spondylitis (AS).

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

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.