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

COMET Study

Evaluation of ENBREL + MTX vs MTX in early moderate to severe rheumatoid arthritis (RA)

COMET Study

Evaluation of ENBREL + MTX vs MTX in early moderate to severe rheumatoid arthritis (RA)

Study Design

The COMET study was a 24-month, multicenter, randomized, double-blind, 2-period study of 542 patients with moderately to severely active RA (from ≥3 months' to ≤2 years' duration) with mean disease duration of 9 months and mean baseline disease activity score (DAS) 28 score of 6.5.1 In Year 1 of the study, patients were randomized to receive once-weekly ENBREL 50 mg + weekly methotrexate (MTX), up to 20 mg/week (n=274); or MTX alone (n=268).1 At Year 2, the original combination group either continued combination therapy (n=108) or received ENBREL monotherapy (n=108); the original MTX monotherapy group either received combination therapy (n=88) or continued MTX monotherapy (n=94).1,2

Additional Study Details

plus-img minus-img
  • Primary endpoints: DAS 28 remission (DAS 28 <2.6) at Year 1 and change from baseline modified total Sharp score (mTSS) at Year 11
  • Select secondary endpoints: Health assessment questionnaire (HAQ) score at Year 1, HAQ score at Year 2, ACR 20 at Year 1, ACR 70 at Year 11,2

Year 1 COMET Study Arms1 (N=542)

Year 2 COMET Study Arms2

Year 1 COMET Study Arms (N=542) and Year 2 COMET Study Arms

Year 1 COMET Study Arms1 (N=542)

Year 1 COMET Study Arms (N=542) and Year 2 COMET Study Arms

Year 2 COMET Study Arms2

Year 1 COMET Study Arms (N=542) and Year 2 COMET Study Arms

a One subject (group 1A) discontinued at final Year 1 visit but received 1 dose of study drug in Year 2 and was included in the Year 2 population.

Select Baseline Demographics1

Mean age 51 years
Percent male/female 26.7%/73.3%
Mean disease duration 9.0 months
Mean HAQ 1.7
Mean DAS 28 6.5
Mean tender joint count 25
Mean swollen joint count 17

References:

  1. Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382.
  2. Emery P, Breedveld FC, van der Heijde D, et al; for the Combination of Methotrexate and Etanercept in Early Rheumatoid Arthritis Trial Group. Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomised study. Arthritis Rheum. 2010;62:674-682.

Primary Endpoint and ACR Results

Primary endpoint results
  • DAS 28 remission (DAS 28 <2.6) was achieved by 49.8% of patients with ENBREL + MTX vs 27.8% with MTX at Year 1 (P<0.001)3
  • Change from baseline in mTSS at Year 1 was 0.27 for ENBREL + MTX vs 2.44 for MTX (P<0.001)1,4
ACR results
  • ACR 20 was achieved by 86% of patients with ENBREL + MTX vs 67% of patients with MTX at Year 1 (P<0.0001)1
  • ACR 50 was achieved by 71% of patients with ENBREL + MTX 49% of patients with MTX at Year 1 (P<0.0001)1
  • ACR 70 was achieved by 48% of patients with ENBREL + MTX vs 28% of patients with MTX at Year 1 (P<0.0001)1

Signs and Symptoms

Significant Symptom and CRP Improvement as Early as Week 2 and Out to Year 1 vs MTX Alone (LOCF)1,3

Significant Symptom and CRP Improvement as Early as Week 2 and Out to Year 1 vs MTX Alone (LOCF) Significant Symptom and CRP Improvement as Early as Week 2 and Out to Year 1 vs MTX Alone (LOCF)
  • Week 2 morning stiffness mean change from baseline: 171 for ENBREL + MTX vs 29 for MTX alone3
  • Year 1 morning stiffness mean change from baseline: 250 for ENBREL + MTX vs 137 for MTX alone3
  • Week 2 painful joint count mean improvement from baseline: -10 for ENBREL + MTX vs -3 for MTX alone3
  • Year 1 painful joint count mean improvement from baseline: -20 for ENBREL + MTX vs -15 for MTX alone3

a ENBREL + MTX: n=265, MTX n=262.

b ENBREL + MTX: n=265, MTX n=263.

c ENBREL + MTX demonstrated a mean reduction of 27 mm on a visual pain scale at Week 2 compared to 8 mm for MTX alone.

d ENBREL + MTX: n=262, MTX n=258.

CRP = C-reactive protein; LOCF = last observation carried forward.

Physical Function

ENBREL + MTX can help your patients get back to their everyday activities
Percentage of Patients Who Achieved HAQ ≤0.5 (LOCF)2,3,5,a
Percentage of Patients Who Achieved HAQ Less than or Equal to 0.5 (LOCF) Percentage of Patients Who Achieved HAQ Less than or Equal to 0.5 (LOCF)

a Patients were randomly assigned to 1 of 4 treatment groups (Group 1A, 1B, 2A, or 2B) at the beginning of the study. During Year 1 of the study, Groups 1A and 1B were combined in the ENBREL + MTX treatment arm, and Groups 2A and 2B were combined in the MTX treatment arm. Not all subjects randomized to Year 2 groups were present in the Year 2 efficacy population, due to withdrawals during Year 1. See Study Design for more information about the Year 1 and Year 2 study populations.2

  • Mean HAQ score at baseline was 1.65 in the MTX arm (n=94), 1.62 in the ENBREL + MTX → ENBREL arm (n=108), and 1.76 in the ENBREL + MTX arm (n=108). At Year 2, mean HAQ score was 0.79 in the MTX arm, 0.65 in the ENBREL + MTX → ENBREL arm, and 0.58 in the ENBREL + MTX arm5†

* HAQ score of ≤0.5 is consistent with the score of the general population.5

The data points shown at Year 1 represent results for combined study arms (Group 1A + Group 1B and Group 2A + Group 2B) reported at the end of Year 1 of treatment. For the study populations entering Year 2 of treatment, the percentages of patients who had achieved HAQ ≤0.5 at the Year 1 time point were 57%, 62%, 51%, and 43% in Groups 1A, 1B, 2A, and 2B respectively.5

Joint Damage

ENBREL + MTX helps stop further progression of joint damage by Year 12
  • 75% of patients taking ENBREL + MTX had no progression of joint damage at Year 1 (n=246) vs 54% of patients taking MTX alone (n=230)4‡

No progression is defined as a change in mTSS ≤0.0 from baseline.4

Clinical Remission

ENBREL + MTX can help your patients achieve clinical remission

Percentage of Patients Achieving DAS 28 Remission (<2.6) (LOCF)1,3

Percentage of Patients Achieving DAS 28 Remission (Less than 2.6) (LOCF) Percentage of Patients Achieving DAS 28 Remission (Less than 2.6) (LOCF)
  • 50% of patients taking ENBREL + MTX achieved DAS 28 remission vs 28% of patients taking MTX at Year 11
  • Clinical remission does not mean drug-free remission or complete absence of disease6
DAS 28 clinical remission was observed in 7 out of 10 patients when treated earlier (post hoc sub-group analysis of very early RA)6
  • In a post hoc analysis, observed data were analyzed by baseline disease duration (very early RA: ≤4 months, early RA: 4 months to 2 years) and by treatment group (ENBREL + MTX and MTX alone). COMET was not prospectively designed to compare patients with very early RA to those with early RA6
  • 70% of ENBREL + MTX patients (n=63) treated very early vs 35% of MTX patients (n=49) treated very early achieved DAS 28 remission at Year 16
  • Baseline mean DAS 28 scores in patients with very early RA were 6.6 for the ENBREL + MTX arm and 6.7 for the MTX arm6
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn. Interpretation of the results of post hoc analysis is limited

TEMPO Study

Evaluation of ENBREL + MTX vs MTX in moderate to severe RA patients who had failed ≥1 DMARD other than MTX

 

TEMPO Study

Evaluation of ENBREL + MTX vs MTX in moderate to severe RA patients who had failed ≥1 DMARD other than MTX

 

Study Design

The TEMPO Study was a 3-year multicenter, double-blind, randomized, controlled trial (RCT) of 682 patients in Europe, Australia, and Israel with moderate to severe RA (mean disease duration 7 years) who had failed ≥1 disease-modifying antirheumatic drug (DMARD) other than MTX.7-9 Patients received either ENBREL 25 mg biweekly (BIW) + MTX (n=231), ENBREL 25 mg BIW + placebo (n=223), or placebo + MTX (n=228) over 3 years. Use of concomitant corticosteroids and/or NSAIDs was permitted.9-12

Additional Study Details

plus-img minus-img
  • Primary endpoints: Numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks and change from baseline in mTSS at Year 11
  • Select secondary endpoints: ACR 20, ACR 50, ACR 70, CRP, HAQ score, and DAS 28 clinical remission2

References:

  1. van der Heijde D, Klareskog L, Boers M, et al; TEMPO Investigators. Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results. Ann Rheum Dis. 2005;64(11):1582-1587.
  2. van der Heijde D, Klareskog L, DeJager J, et al; the TEMPO Trial Investigators. Radiographic outcomes of a double-blind study of etanercept and methotrexate, alone and combined, in active patients with rheumatoid arthritis (the TEMPO trial). Poster presented at: 67th Annual Scientific Meeting of the American College of Rheumatology; October 24-28, 2003; Orlando, FL.

Primary Endpoint and ACR Results

Primary endpoint results:
  • ACR-N AUC was 18.3%-years (95% CI, 17.1-19.6) for ENBREL + MTX, 14.7%-years (95% CI, 13.5-16.0) for ENBREL monotherapy, and 12.2%-years (95% CI, 11.0-13.4) for MTX monotherapy at Week 2413§
  • Mean change in mTSS was -0.5 for ENBREL + MTX, 0.2 for ENBREL monotherapy (P<0.01), and 1.9 for MTX monotherapy (P<0.01) at Year 114,15
ACR results:
  • ACR 20 response (nonresponder imputation) at Week 2 was 44% for ENBREL + MTX and 19% for MTX alone16
  • ACR 20/50/70 rates at Week 4 were 58%/20%/7% for ENBREL + MTX and 34%/4%/0% for MTX alone13,16
  • ACR 20/50/70 rates at Year 3 were 52%/43%/31% for ENBREL + MTX and 33%/24%/13% for MTX alone (NRI)16¶
  • A higher percentage of patients treated with ENBREL and ENBREL + MTX achieved ACR 20, ACR 50, and ACR 70 responses and Major Clinical Responses than in the comparison groups7**

§ ENBREL + MTX vs MTX (P<0.0001); ENBREL vs MTX (P=0.0034); ENBREL MTX vs ENBREL (P<0.0001).

Non-Responder Imputation.

** Major clinical response is achieving an ACR 70 response for a continuous 6-month period.

Signs and Symptoms

ENBREL + MTX helps patients feel less joint pain and morning stiffness
Reductions in Pain, Morning Stiffness, and C-Reactive Protein (CRP)17
Reductions in Pain, Morning Stiffness, and C-Reactive Protein (CRP) Reductions in Pain, Morning Stiffness, and C-Reactive Protein (CRP)
  • ENBREL + MTX provided rapid and sustained improvements in clinical signs and symptoms as early as Week 2 and out to Year 316

Physical Function

ENBREL + MTX can help patients get back to their everyday activities

Reductions in HAQ Scores (%)17

Reductions in HAQ Scores (%) Reductions in HAQ Scores (%)

a P<0.01.

ITT = intent-to-treat.

  • ENBREL + MTX provided rapid and sustained improvements in HAQ scores by Week 2 and out to Year 314
  • Mean HAQ score at baseline, Week 2, and Year 3 were 1.7, 1.5, and 1.1 in the MTX arm and 1.8, 1.3, and 0.8 in the ENBREL + MTX arm, respectively14,17

Percentage of Patients Who Achieved HAQ ≤0.5 (LOCF)17

Percentage of Patients Who Achieved HAQ Less Than or Equal to 0.5 (LOCF) Percentage of Patients Who Achieved HAQ Less Than or Equal to 0.5 (LOCF)
  • Half of ENBREL patients achieved a HAQ score consistent with the general population (HAQ ≤0.5)17††
  • Mean HAQ score at baseline was 1.7 in the MTX arm (n=228) and 1.8 in the ENBREL + MTX arm (n=231). At Year 3, mean HAQ score was 1.1 in the MTX arm and 0.8 in the ENBREL + MTX arm10,17

†† HAQ score of ≤0.5 is consistent with the score of the general population.18

Joint Damage

ENBREL + MTX can help stop the progression of joint damage

Mean Change in mTSS14,15

Mean Change in mTSS Mean Change in mTSS

a P<0.01 vs MTX;  b P<0.05 vs MTX; c P<0.01 vs ENBREL.

  • Patients treated with ENBREL + MTX or ENBREL monotherapy experienced significant inhibition of joint damage through Year 314,15,19,20‡‡
  • ENBREL + MTX and ENBREL monotherapy resulted in significantly less radiographic progression compared with MTX alone14,15
  • Patients with no radiographic progression (Δ mTSS ≤0) at 3 years: 73% in the ENBREL + MTX arm, 60% on ENBREL alone, and 50% on MTX alone15

‡‡ Per protocol, in order to read the Year 3 data (N=638), the Year 1 (N=648) and Year 2 data (N=622) were reread. Because of known variability in reading of the radiographic images in RA, all radiographs were reread and blinded to patient and time point by the 2 physicians who read the images for the Year 2 report. Thus, the Year 3 scoring of the of the radiographic images is considered a new reading of the Year 1 and Year 2 time points.

Clinical Remission

ENBREL + MTX helps patients achieve clinical remission

Percentage of Patients Who Achieved DAS 28 Clinical Remission21

Percentage of Patients Who Achieved DAS 28 Clinical Remission Percentage of Patients Who Achieved DAS 28 Clinical Remission
  • Patients treated with ENBREL + MTX experienced rapid and sustained DAS 28 remission by Week 4 and out to Year 321
  • DAS 28 clinical remission does not mean drug-free remission or complete absence of disease21

ERA Study

Evaluation of ENBREL and MTX in early moderate to severe RA, including an analysis of MTX discontinuation

ERA Study

Evaluation of ENBREL and MTX in early moderate to severe RA, including an analysis of MTX discontinuation

 

Study Design

The Early RA (ERA) Study was a 1-year, multicenter, randomized, double-blind study of 632 patients with early moderately to severely active RA (≤3 years' duration) with mean disease duration of 11.2 months.7,22,23 In Year 1 of the study, patients were randomized to receive ENBREL 10 mg BIW (n=208), ENBREL 25 mg BIW (n=207), or MTX (up to 20 mg/week, n=217). At Year 2, patients continued in an open-label treatment period. At Year 3, patients switched to or continued ENBREL 25 mg BIW for an open-label extension (n=468). MTX could be continued or started as necessary in the open-label extension (OLE) at the investigator's discretion.24-26

  • All statistical analyses conducted during the OLE are considered descriptive and not confirmatory and therefore are not presented. Consider the following limitations when evaluating OLE results:

    • There is no concurrent control arm, limiting the estimate of treatment effect
    • Data are based only on patients who continued taking ENBREL at each year. Reasons for discontinuation included lack of tolerability, lack of efficacy, and loss to follow-up. Response rates may represent an enriched proportion of patients with continued efficacy and tolerability

Additional Study Details

plus-img minus-img
  • Primary endpoints: Numeric index of the ACR-N AUC at Month 6 and change from baseline in mTSS at Year 11
  • Baseline patient demographics: Mean age was 50 years, 25% of patients were male, and mean disease duration was 11.2 months.2-3

The ERA Study3-5,a

The ERA Study The ERA Study

a At the end of Year 2, patients switched to or continued on ENBREL 25 mg BIW.

References:

  1. Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-1593.
  2. Data on file, Amgen; 1623 ERA 5 yr. October 20, 2003.
  3. Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002;46:1443-1450.
  4. Weinblatt ME, Baten JM, Kremer JM, et al. Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011;63(3):373-382.
  5. Genovese MC, Bathon JM, Fleischmann RM, et al. Long-term safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005;32:1232-1242.

Primary Endpoints

  • ACR-N AUC was 15.3 with ENBREL vs 11.5 with MTX at Month 6 (P<0.05)25,27
  • Change from baseline in mTSS was 1.00 with ENBREL vs 1.59 with MTX at Year 1 (P=0.11)25

MTX and Corticosteroid Use

Percent of ENBREL Patients Who Reduced or Discontinued MTX and Corticosteroids23,24

Percent of ENBREL Patients Who Reduced or Discontinued MTX and Corticosteroids Percent of ENBREL Patients Who Reduced or Discontinued MTX and Corticosteroids

a Patients who received MTX during the first 2 years of the study and who started ENBREL in the OLE.

b Change from baseline of OLE.

c Patients who received ENBREL during the first 2 years of the study and continued taking ENBREL in the OLE.

d Change from baseline.

  • Continued durable responses were seen for over 60 months in OLE treatment studies when patients received ENBREL without interruption. A substantial number of patients who initially received concomitant MTX or corticosteroids were able to reduce their doses or discontinue these concomitant therapies while maintaining their clinical responses7,23

Mean Dose Reductions of MTX and Corticosteroids in ENBREL Patients24

Mean Dose Reductions of MTX and Corticosteroids in ENBREL Patients Mean Dose Reductions of MTX and Corticosteroids in ENBREL Patients

a Patients who received MTX during the first 2 years of the study and who started ENBREL in the OLE.

b Patients who received ENBREL during the first 2 years of the study and continued taking ENBREL in the OLE.

c Change from baseline of OLE.

d Change from baseline.

  • Among 110 patients who received MTX during the first 2 years of the study and who switched to ENBREL during the long-term OLE, 71 were able to discontinue and 20 were able to decrease their dose, 14 maintained their dose, and 5 increased their dose after 3 years in OLE23
  • At 5 years, 44 of 162 patients receiving ENBREL in both the randomized, controlled trial and OLE had also received corticosteroids during the study. Of those 44 patients, 27 were able to discontinue their corticosteroid, 6 were able to decrease their dose, 10 maintained their dose, and 1 increased their dose23,24

Joint Damage

Long-term inhibition of further joint damage through Year 5
  • Change from baseline in mTSS was 1.00 with ENBREL vs 1.59 with MTX at Year 1 (P=0.11)25
  • 48% of the original patients treated with ENBREL were evaluated radiographically at 5 years24
55% had no radiographic progression through 5 years 55% had no radiographic progression through 5 years

No progression is defined as a change in mTSS ≤0.0 from baseline; n=297.

Clinical Remission

A 10-year post hoc analysis of the ERA Study of moderately to severely active early RA
  • >4 out of 10 ENBREL patients had DAS 28 remission at 10 years28

Percentage of Patients Who Achieved DAS 28 Remission (<2.6) (as Observed)28,29,a

Percentage of Patients Who Achieved DAS 28 Remission (Less than 2.6) (as Observed) Percentage of Patients Who Achieved DAS 28 Remission (Less than 2.6) (as Observed)

aIn this study, a modified DAS, DAS 28, was utilized based on a 28-joint count (28 tender and 28 swollen). DAS 28 clinical remission is defined as DAS 28 <2.6 units.

bPatients were administered ENBREL 25 mg BIW monotherapy for the first 2 years, then continued on ENBREL 25 mg BIW with the option to add MTX at any point during the remainder of the study.

cBaseline: n=217; Year 1: n=192; Year 2: n=138.

Limitations of DAS 28 post hoc analysis and OLE
  • DAS 28 was retrospectively calculated based on data collected during the study
  • DAS 28 was not a prespecified endpoint in the controlled portion of the study and was calculated post hoc for each study period from baseline to 10 years
  • Post hoc analysis is exploratory and no statistical conclusions can be drawn
  • There is no concurrent control arm, limiting the estimate of treatment effect
  • Data are based only on patients who continued taking ENBREL at each year. Reasons for discontinuation included lack of tolerability, lack of efficacy, and loss to follow-up. Response rates may represent an enriched proportion of patients with continued efficacy and tolerability

MODERATE TO SEVERE RHEUMATOID ARTHRITIS

Learn about RA 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.