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

Ankylosing Spondylitis (AS) Trial

Ankylosing Spondylitis (AS) Trial

Study Design

The AS Trial was a 24-week, multicenter,1 double-blind, randomized, placebo-controlled, phase 3 trial of 277 patients with active AS (mean disease duration of 10 years) who did not have complete spinal fusion. Patients were randomized to receive ENBREL 25 mg twice weekly (BIW, n=138) or placebo BIW (n=139).2

Additional Study Details

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  • Primary endpoint: Assessment in SpondyloArthritis International Society (ASAS) 20 response1
  • Select secondary endpoint: ASAS 50 response1
  • NSAIDs and corticosteroids were allowed if doses remained stable for 2 weeks before the study start and throughout the study; methotrexate (MTX), sulfasalazine, or hydroxychloroquine were allowed if doses remained stable for 4 weeks before baseline and throughout the study. Of 277 patients randomized, 44 (32%) of the ENBREL group and 43 (31%) of the placebo group were receiving concomitant MTX, sulfasalazine, or hydroxychloroquine at baseline1,2
  • For the purposes of this study, ASAS 20 response (primary measure of efficacy) was defined as improvement of ≥20% and absolute improvement of ≥10 units (on a scale of 0 to 100) in at least 3 of 4 ASAS domains and absence of deterioration in the remaining domain1
  • The 4 ASAS domains included patient global assessment measured on a visual analog scale (VAS) of “none” to “severe”; pain assessment (the average of nocturnal and total pain scores, both measured on a VAS of “no pain” to “most severe pain”); function (the average of 10 questions on the Bath Ankylosing Spondylitis Functional Index (BASFI) measured on a VAS of “easy” to “impossible;” and inflammation (the average of 2 questions regarding morning stiffness on the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) measured on a VAS: one (No. 5) of “none” to “very severe”; the other (No. 6) by duration of morning stiffness between “0” and “2” or more hours1,2
  • ASAS 50 and 70 responses indicated ≥50% and ≥70% improvement in 3 of the 4 listed components in addition to the ≥10-point absolute improvement. Deterioration for the remaining domain for each assessment was defined as worsening of ≥20% and a decline of ≥10 units on a 0 to 100 scale1
  • One patient in the placebo group had a score of 0 at baseline and was not included in the analysis of percent improvement in nocturnal pain assessment from baseline2

References:

  1. Davis JC Jr, van der Heijde D, Braun J, et al; Enbrel Ankylosing Spondylitis Study Group. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. 2003;48(11):3230-3236.
  2. Data on file, Amgen; CSR 1637. December 20, 2002.

ASAS Response

Patients saw improved ASAS 20 response with ENBREL3
  • Primary endpoint: At Week 12, 60% of patients taking ENBREL achieved ASAS 20 vs 27% of patients taking placebo (P<0.0001);at Week 24, 58% of patients taking ENBREL achieved ASAS 20 vs 23% of patients taking placebo (P<0.0001)4
Results were similar between ENBREL monotherapy and ENBREL + a disease modifying antirheumatic drug (DMARD) in a post hoc analysis5
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn

ASAS 20 Response3-5

ASAS 20 Response

ASAS 20 Response

a Patients were stratified by concomitant DMARD.2

ASAS 50 and 70 results for ENBREL monotherapy and ENBREL + a DMARD at Week 24 in a post hoc analysis4,5
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn

Percent of Patients Achieving ASAS 50 and 704,5

Primary Analysis Post Hoc Analysis
Placebo
(n=139 )
ENBRELa
(n=138)
ENBREL
monotherapy
(without a
DMARD, n=94)
ENBREL + a
DMARD
(n=44)
ASAS 50 10% 42% 38% 50%
ASAS 70 5% 28% 28% 30%

a Included patients on ENBREL + a DMARD (hydroxychloroquine, sulfasalazine, or MTX, n=44) and ENBREL monotherapy without a DMARD (n=94).

Back Pain

ENBREL decreased back pain for patients
  • At 24 weeks, patients taking ENBREL reported a 35% improvement in back pain from baseline compared to 5% in patients taking placebo (P<0.0001)4
Results were similar between ENBREL monotherapy and ENBREL + a DMARD in a post hoc analysis4,5
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn
  • Patients taking ENBREL monotherapy and ENBREL + a non-biologic DMARD experienced a 36% and 46% mean improvement in nocturnal back pain respectively at Week 245

Change in Total Back Pain3-5,a

Change in Total Back Pain

Change in Total Back Pain

a Average of nocturnal and total back pain.

b Includes patients on ENBREL + a DMARD (hydrocychloroquine, sulfasalazine, or MTX, n=44) and ENBREL monotherapy (without a DMARD, n=94).

Physical Function

ENBREL helped improve functional measures for patients
  • Patients taking ENBREL demonstrated a 30% improvement from baseline in BASFI* score response compared to 2% in patients taking placebo at 24 weeks (P<0.0001)2,3
Results were similar between ENBREL monotherapy and ENBREL + a DMARD in a post hoc analysis
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn

Change in BASFIa at
Week 242-5

Change in BASFI at Week 24

Change in BASFI at Week 24

Change in BASFI at Week 24

a Measured on a VAS of 0-100.

b Patients were stratified by concomitant DMARD.

*The BASFI is a patient self-assessment tool to measure disease activity based on an average of 10 questions.

Signs and Symptoms

Results for ENBREL monotherapy and ENBREL + a DMARD in a post hoc analysis
  • ENBREL helped patients demonstrate statistically significant improvements in all disease activity2†
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn4

Improvement in Signs and Symptoms at Week 243-5

Improvement in Signs and Symptoms at Week 24

Improvement in Signs and Symptoms at Week 24

Improvement in Signs and Symptoms at Week 24

Improvement in Signs and Symptoms at Week 24

a Includes patients on ENBREL + a DMARD (hydroxychloroquine, sulfasalazine, or MTX) (n=44) and ENBREL monotherapy (without a DMARD) (n=94).

As represented in spinal mobility measures, including modified Schober's test, chest expansion score, and occiput-to-wall measurements.2

ANKYLOSING SPONDYLITIS 

Learn about the AS 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.