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

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

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

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

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

ENBREL clinical study designs

ENBREL has been evaluated in clinical studies over the past 20 years. Clinical research in RA patients began in 1993.1 The key clinical studies for the safety and efficacy of ENBREL are detailed below.

 

Moderate to Severe Rheumatoid Arthritis (RA)

  • Multi-center, double-blind RCT of 682 patients in Europe, Australia, and Israel with moderate to severe RA (mean disease duration 7 years) who had failed ≥ 1 DMARD other than MTX received either ETN 25 mg BIW + MTX (n=231), ETN 25 mg BIW + placebo (n=223), or placebo + MTX (n=228) over 3 years1,2
  • Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted2
  • The primary clinical endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks2
  • The primary radiographic endpoint was the change from baseline in TSS at 12 months2

TEMPO References:

  1. Enbrel® (etanercept) Prescribing Information, Immunex Corporation, Thousand Oaks, Calif. 03/2015.
  2. Klareskog L, van der Heijde D, de Jager JP, et al; for the TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-681.
  • 24-month, multicenter, randomized, double-blind, 2-period study of 542 patients with moderately to severely active early RA (from ≥3 months' to ≤2 years' duration) with mean disease duration of 9 months1
  • During Period 1 (Year 1) of the study, patients were randomized to receive once-weekly ENBREL 50 mg in combination with weekly MTX (up to 20 mg/week; n=274) or MTX alone (n=268)1
  • At Period 2 (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 monotherapy (n=94)2
  • The primary objective was to compare the effects of ENBREL + MTX to MTX on clinical disease activity and radiographic change over 1 year1

    Primary efficacy endpoints3

    • Proportion of patients achieving remission (DAS 28 <2.6)
    • Change in mTSS from baseline at 52 weeks

    Primary endpoint efficacy results1,3,4

    • 49.8% of patients achieved DAS 28 remission with ENBREL + MTX vs 27.8% with MTX at Week 52 (P<0.001)
    • Change from baseline in mTSS at 52 weeks was 0.27 for ENBREL + MTX vs 2.44 for MTX (P<0.001)

COMET 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, randomized study. Arthritis Rheum. 2010;62:674-682.
  3. Data on file, Amgen; 69344 COMET 1 yr: September 18, 2007.
  4. Data on file, Amgen; COMET CSR 71630 1 yr X-ray: December 7, 2007.
  5. Data on file, Amgen; COMET Safety Population. May 7, 2009.
  • Multicenter, double-blind, double-dummy, Phase 3 study 1,2
  • 632 MTX-naïve patients with early moderately to severely active RA (≤3 years’ duration) were randomized to receive twice-weekly ENBREL 25 mg (n=207), twice-weekly ENBREL 10 mg (n=208), or MTX (n=217). The mean duration of disease for these patients was 11 to 12 months1-3
  • Baseline patient demographics: mean age was 50 years, 25% of patients were male, mean disease duration was 11.2 months, and the mean DAS 28 score was 5.41,2,4,5
  • This study became open-label and unblinded after all patients had completed 1 year of evaluation. Patients continued through 1 year of follow-up on the treatment to which they had been randomized. At the end of Year 2, patients switched to or continued twice-weekly ENBREL 25 mg subcutaneously1,2,4,6

The ERA Study1,2,4,6*

    Primary efficacy endpoints and results

    • Primary endpoints were area under curve (AUC) for the numeric ACR score over 6 months and modified Total Sharp Score (mTSS) over 12 months3
    • ACR-N area under the curve was 15.3 with ENBREL vs 11.5 with MTX at Month 6 (P=0.002)
    • Change from baseline in mTSS was 1.00 with ENBREL vs 1.59 with MTX at Year 1 (P=0.11)3

    OLE overview and limitations

    • Patients who completed at least 1 year in the ERA randomized controlled trial (RCT) study were eligible for enrollment into OLE5,6
    • MTX could be continued or started as necessary in the OLE at the investigator's discretion4
    • All statistical analyses conducted during the OLE are considered descriptive and not confirmatory, and therefore are not presented in this piece
    • 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

ERA Study References:

  1. Enbrel® (etanercept) Prescribing Information, Immunex Corporation, Thousand Oaks, Calif.
  2. Data on File, Amgen. 1623 ERA 5 yr 10/2003.
  3. Bathon JM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-1593.
  4. Genovese MC, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002;46:1443-1450.
  5. Genovese MC, et al. Long-term safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005;32:1232-1242.
  6. Data on File, Amgen. 1623 ERA Final 12/2009.

Moderate to Severe Plaque Psoriasis (PsO)

  • The ENBREL Global Psoriasis Pivotal Trial was a multicenter, double-blind, randomized, phase 3 trial of 611 adult patients with active but clinically stable plaque PsO involving at least 10% of body surface area (BSA) and a minimum PASI score of 10. However, 583 patients received at least one dose of study drug and were included in the primary analysis. Patients received ENBREL 50 mg, 25 mg, or placebo twice weekly (BIW) over 12 weeks. After 12 weeks, all patients received open-label ENBREL 25 mg BIW. Patients were limited to low- to moderate strength topical corticosteroids in the axillary, groin, and scalp regions.1,2
  • A post hoc analysis was conducted for the OLE, a singular study comprised of patients from 2 parent trials, the Global Psoriasis Pivotal Trial and the US Psoriasis Pivotal Trial. Patients from the Global Psoriasis Pivotal Trial had the option to enroll in the OLE after completing a minimum of 36 weeks1,3,4
  • 473 total patients enrolled in the OLE from the Global Psoriasis Pivotal Trial out of a possible 583 patients who had received at least 1 dose of ENBREL3
  • Dosing: Patients were randomized to receive subcutaneous injections of ENBREL 50 mg, ENBREL 25 mg, or placebo administered BIW over 12 weeks. After 12 weeks, patients received open-label ENBREL 25 mg BIW. However, in the open-label portion, physicians and patients remained blinded to the original randomized dosing arm through 6 months1,2
  • OLE Dosing: All patients received ENBREL 50 mg QW for the first 12 weeks. At Week 13, eligible patients were given the option to stay on ENBREL 50 mg QW. Patients completed between 48 weeks and 72 weeks of treatment in the OLE3
  • Primary endpoint: PASI 75 achievement after 12 weeks of double-blind treatment1
  • Secondary endpoints: PASI 50 and 90 achievement, percent improvement from baseline PASI, static global assessment of psoriasis clear or almost clear, and the patient’s global assessment of psoriasis at Weeks 12, 24, and 481
  • Primary OLE endpoints: Incidence of adverse events, infectious episodes, serious adverse events, serious infectious episodes, injection site reactions, changes from baseline in laboratory values, and presence/absence of an antibody response3
  • Secondary OLE endpoints: PASI 50, 75, and 90 achievement, percent improvement from baseline* PASI, static global assessment of psoriasis clear or almost clear, and the patient’s global assessment of psoriasis at Weeks 12, 24, and 483

Global Psoriasis Pivotal Trial1,2
(N=583)

Select baseline demographics5

Age (mean) 45 years
Male 66%
Caucasian 91%
Weight (mean) 194 lbs
Body mass index (mean) 30
BSA Involvement (mean) 28%
PsO duration (mean) 20 years
PASI (mean) 19

Global Psoriasis Pivotal Trial References:

  1. Data on file, Amgen; CSR 1642: October 8, 2003.
  2. Papp KA, Tyring S, Lahfa M, et al; for the Etanercept Psoriasis Study Group. A global phase Ill 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; 115 CSR: November 28, 2005.
  4. Data on file, Amgen; CSR 1639: October 8, 2003.
  5. Data on file, Amgen; CSR 1642 3 month. May 29, 2003.
  • The ENBREL Phase 3 Study was a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of ENBREL 50 mg twice weekly (BIW) vs placebo.1 Patients were ≥18 years old with active but clinically significant plaque psoriasis involving ≥10% body surface area (BSA) and a minimum Psoriasis Area and Severity Index (PASI) score of 10 at screening1
  • Primary endpoint: Percent of patients achieving PASI 75 at Week 121
  • Select secondary endpoint measures: Patient assessment of itching at Week 12; Patient assessment of improvement from baseline in skin pain at Week 12; The severity of skin pain and itch was assessed by patients based on a single-item questionnaire* rating it on a scale of 0 (none) to 5 (severe) for itch, and 0 (none) to 10 (severe) for pain;1 Patient-reported outcomes of itching and improvement from baseline in skin pain at Week 121

Patients with adult chronic moderate to severe plaque PsO1

ENBREL Phase 3 Study Reference:

  1. Data on file, Amgen; CSR 20030117 Week 12 Readout. June 17, 2004.
  • The US Psoriasis Pivotal Trial was a multicenter, double-blind, phase 3 study of patients with active but clinically stable plaque psoriasis involving at least 10% of body surface and a minimum PASI score of 10. Patients had previously received phototherapy or systemic psoriasis therapy at least once or had been a candidate for such therapy. Patients were limited to low- to moderate-strength topical corticosteroids in the axillary, groin, and scalp regions with stable formulation and dosing throughout the study1,2
  • A post hoc analysis was conducted for the OLE, a singular study comprised of patients from 2 parent trials, the Global Psoriasis Pivotal Trial and the US Psoriasis Pivotal Trial. Patients from the US Psoriasis Pivotal Trial had the option to enroll in the OLE after completing a minimum of 60 weeks1,3
  • 439 total patients enrolled in the OLE from the US Psoriasis Pivotal Trial out of a possible 652 patients who had received at least 1 dose of ENBREL3
  • The US Psoriasis Pivotal Trial was designed to assess retreatment after withdrawal. Patients with 50% PASI improvement from baseline at Week 24 discontinued ENBREL treatment. Upon relapse (loss of 50% PASI improvement obtained before Week 24), patients resumed blinded ENBREL therapy at the dose they received from Weeks 13 to 241,4
  • Dosing: US Psoriasis Pivotal Trial: Patients were randomized to receive subcutaneous injections of ENBREL 50 mg BIW, ENBREL 25 mg BIW, ENBREL 25 mg QW, or placebo for 12 weeks. After 12 weeks, patients in the placebo group began treatment with ENBREL 25 mg BIW in a blinded fashion. After 24 weeks, patients were classified as responders (had ≥50% improvement from baseline PASI) or incomplete responders (had <50% improvement from baseline PASI). Responders were entered into the withdraw/retreat portion of the study and were discontinued from treatment and followed until their disease relapsed (loss of ≥50% PASI improvement obtained between baseline and Week 24), at which time patients resumed blinded ENBREL therapy at their dose from Weeks 13 to 241,2
  • OLE Dosing: All patients received ENBREL 50 mg QW for the first 12 weeks. At Week 13, eligible patients were given the option to stay on ENBREL 50 mg QW. Patients completed between 48 weeks and 72 weeks of treatment in the OLE3
  • Primary endpoint: US Psoriasis Pivotal Trial: The primary endpoint was PASI 75 achievement after 12 weeks of double-blind treatment.2,5
  • Secondary endpoints: included 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 psoriasis2,5
  • Primary OLE endpoints: were the incidence of adverse events, infectious episodes, serious adverse events, serious infectious episodes, injection site reactions, changes from baseline in laboratory values, and presence/absence of an antibody response3
  • Secondary OLE endpoints: included PASI 50, 75, and 90 achievement, percent PASI improvement relative to baseline in the parent study, static global assessment of psoriasis clear or almost clear, and the patient’s global assessment of psoriasis at Weeks 12, 24, and 483

US Psoriasis Pivotal Trial1-3
(N=652)

Select baseline demographics4,5

US Psoriasis Pivotal Trial References:

  1. Data on file, Amgen; CSR 1639: October 8, 2003.
  2. 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.
  3. Data on file, Amgen; 115 CSR: November 28, 2005.
  4. Gordon KB, Gottlieb AB, Leonardi CL. et at; for the Etanercept Psoriasis Study Group. Clinical response in psoriasis patients discontinued from and then reinitiated on etanercept therapy. J Dermatolog Treat. 2006;17:9-17.
  5. Data on file, Amgen; CSR 1639: June 11, 2003.
  • The PsO Apremilast Failure Trial was a multicenter, open-label, single-arm, phase 4 estimation study in patients ≥18 years old with moderate to severe plaque PsO with BSA ≥10%, PASI ≥10, and sPGA ≥3 who had failed apremilast. Failed therapy with apremilast (at least 4 weeks of treatment) for chronic moderate to severe plaque PsO was defined as: (1) failure to achieve adequate clinical response in the opinion of the investigator, (2) loss of adequate clinical response in the opinion of the investigator, or (3) intolerability to apremilast in the opinion of the investigator1
  • Primary endpoint: PASI 75 response at Week 121
  • Select secondary endpoints: PASI 75 response at Week 24, PASI 50 and 90 response at Weeks 12 and 24, sPGA response at Weeks 12 and 24, Psoriasis Symptom Inventory (PSI) response at Weeks 12 and 241
PsO Apremilast Failure Trial¹
Select baseline demographics²
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PsO Apremilast Failure Trial¹
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Select baseline demographics²
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PsO Apremilast Failure Trial References:

  1. Data on file, Amgen; CSR 20150252: February 5, 2016.
  2. Data on file, Amgen; Summary of Results 20150252: February 19, 2018.
  • 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 Psoriasis Scalp Severity Index (PSSI) score of 151,2
  • 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)1,2
  • PSSI is a scalp-specific modification of PASI that evaluates the extent of involvement and severity of erythema, infiltration, and desquamation of the scalp in a single score (0–72)1,2
  • The objective of the ENBREL Scalp Involvement Study was to examine the efficacy of ENBREL in patients with moderate to severe plaque PsO with scalp involvement, primarily through PSSI assessments that evaluate plaque involvement of the scalp alone1,2
  • Primary endpoint: percent improvement from baseline PSSI at Week 121,2
  • 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 121,2
  • 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 scalp1,2

ENBREL Scalp Involvement Study References:

  1. 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.
  2. Data on file, Amgen; CSR20080014: July 22, 2010.
  • OBSERVE-5 was a prospective, multicenter, observational surveillance registry evaluating data on long-term safety of ENBREL use in moderate to severe plaque psoriasis1
  • This study was conducted at 375 sites (37 in Canada, 338 in US)1
  • Patients received ENBREL at a dose and regimen determined by the investigator in accordance with the ENBREL Prescribing Information (ENBREL 50 mg twice weekly (BIW)/once weekly (QW) for US patients). The registry included patients from Canada, and these patients received a maintenance dosing regimen that was aligned to the Canadian product monograph (ENBREL 50 mg BIW) and may differ from US Prescribing Information maintenance dosing1,2
  • Patients were able to:
    • Discontinue ENBREL therapy1
    • Switch to another antipsoriatic therapy1
    • Use other antipsoriatic treatments in combination with ENBREL1
    • Discontinue any or all antipsoriatic treatments1
  • Patients were tracked through 5 years at 6-month intervals1
  • Primary endpoint: The occurrence of serious adverse events and serious infectious events1,2
  • Inclusion criteria
    • Patients with moderate to severe plaque psoriasis for whom ENBREL is indicated according to the Prescribing Information2
    • Decision of the treating physician to initiate, reinitiate, or continue ENBREL according to usual care2
    • Obtained appropriate written informed consent prior to any study-specific procedure1,2
  • 2,511 moderate to severe plaque psoriasis patients were administered ENBREL at baseline across 375 study centers in the United States and Canada1
    • 1,455 (58%) continued in the study until the end of follow-up1
    • 164 patients received ENBREL continuously without interruption1
    • 182 patients received ENBREL throughout the study with 1–30 day gaps1*
    • 63 patients received ENBREL throughout the study with 31–60 day gaps1*
    • Of patients who experienced gaps in ENBREL treatment, most had only 1 or 2 gaps1*
  • A limitation of this study was a lack of an internal comparator1
  • The size and duration of the study may not have been sufficient to detect extremely rare adverse events that may be related to treatment1
  • Interpretation of standardized incidence ratios should consider differences in data collection methods, sampling designs, and study populations in a prospective registry vs an administrative claims database compiled for billing purposes1
  • Interpretation of safety and effectiveness-related outcomes should take into account the 42% drop-out rate, which may lead to an underestimation of safety events and an overestimation of effectiveness if discontinuation was related to these outcomes1

OBSERVE-5 study design1

ENBREL 5-year Observational Registry (OBSERVE-5) References:

  1. Kimball AB, Rothman KJ, Kricorian G, et al. OBSERVE-5: observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results. J Am Acad Dermatol. 2015;72:115-122.
  2. Data on file, Amgen; CSR 20040210 OBSERVE-5: June 28, 2011.
  • A 48-week, randomized, double-blind, placebo-controlled US and Canadian study (parent study) in 211 patients with moderate to severe plaque PsO between 4 and 17 years of age1
  • The 48-week parent study was followed up by a long-term 264-week (5-year; n=182) open-label extension1
  • Patients were dosed 0.8 mg/kg up to a maximum dose of 50 mg QW. No loading dose or dose adjustments were made except for those based on weight1
  • 42% of all patients (n=89/211) had a baseline weight of >62.5 kg (>138 lb)2
    • Of the 89 patients, 47 received the maximum dose of ENBREL 50 mg QW and 42 received placebo QW during the 12-week, randomized, double-blind, treatment phase2

Open-label extension

  • Long-term safety profile for up to 264 additional weeks was assessed in an open-label extension study; no new safety signals were identified1
  • Primary endpoints: Subject incidence of adverse events, including infectious episodes, serious adverse events, and serious infectious episodes5
  • Secondary endpoints: PASI 50/75/90 and sPGA of “clear” or “almost clear”30

Pediatric Pivotal Study References:

  1. Enbrel® (etanercept) Prescribing Information, lmmunex Corporation, Thousand Oaks, Calif.
  2. Data on file, Amgen; Number of subjects with baseline weight over certain threshold: September 20, 2016.
  3. Data on file, Amgen; CSR 20030211 Pediatric PsO double-blind: September 18, 2006.
  4. Data on file, Amgen; CSR 20030211 Pediatric PsO final: July 16, 2007.
  5. Data on file, Amgen; CSR 20050111 Pediatric PsO OLE: June 1, 2012.

Psoriatic Arthritis (PsA)

  • Multi-center, double-blind, phase 3 study of 205 patients with active PsA1,3,4
  • Mean duration of arthritic disease was about 9.1 years and mean duration of plaque psoriasis was about 19.0 years (with a qualifying target skin lesion)1,4
  • Patients were randomized to receive subcutaneous injections of ENBREL 25 mg (n=101) or placebo (n=104) administered twice weekly over the 24-week blinded treatment period1,3
  • After the 24-week period, patients continued therapy in a maintenance period of up to 6 months until all patients completed double-blind therapy. After the maintenance period, all patients received ENBREL 25 mg twice weekly in an open-label period of 48 weeks1,3
  • Of the 205 patients enrolled in the randomized phase of the study, 169 (88 originally randomized to ENBREL; 81 originally randomized to placebo) entered the open-label extension. Concomitant use of MTX, NSAID, corticosteroids, and topical therapies were permitted at the discretion of the investigator1,2
  • Nonresponder imputation analysis was conducted during the double-blind portion for ACR response and skin lesion clearing, while parameters assessed during the open-label period were analyzed based on the observed population at each time point1
  • The primary efficacy endpoint was ACR 20 at 12 weeks1
  • The primary radiographic endpoint was the annualized rate of change in TSS over 1 year of treatment1
  • TSS is based on combined scores of joint erosions in the hands and wrists on a scale of 0 to 5 (0=no damage) and joint space narrowing in the hands and wrists on a scale of 0 to 4 (0=no narrowing) and was modified to include an assessment of the distal interphalangeal joints. Data are shown for all patients having a 2-year radiograph (n=141).1,2,5

Psoriatic Arthritis Pivotal Study References:

  1. Data on file, Amgen. 1630 PsA 2 yr 08/2004.
  2. Mease PJ, Kivitz AJ, Burch FX, et al. Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. J Rheumatol. 2006;33:712-721.
  3. Enbrel® (etanercept) Prescribing Information, Immunex Corporation, Thousand Oaks, Calif. 03/2015.
  4. 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.
  5. van der Heijde DM. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol. 2000;27:261-263.
  • 24-week, randomized, multicenter outpatient study of 752 patients with chronic moderate to severe plaque PsO and PsA1
  • Patients were randomized to receive either ENBREL 50 mg BIW or ENBREL 50 mg + placebo QW for 12 weeks. All patients then received ENBREL 50 mg QW during a 12-week open-label period1
    • Note that the recommended dose of ENBREL for adult patients with PsA is 50 mg QW and for adult moderate to severe plaque PsO patients is 50 mg BIW for 3 months followed by reduction to a maintenance dose of 50 mg QW2

The PRESTA study design1

Select baseline demographics1,3

Psoriasis Randomized Etanercept Study in Subjects with Psoriatic Arthritis (PRESTA) References:

  1. Data on file, Amgen; PRESTA CSR 73764: February 17, 2009.
  2. Enbrel® (etanercept) Prescribing Information, Immunex Corporation, Thousand Oaks, Calif.
  3. Sterry W, Ortonne JP, Kirkham B, et al. Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial. BMJ. 2010;340:c147.

Ankylosing Spondylitis (AS)

  • Multi-center, double-blind, randomized, placebo-controlled Phase 3 trial of 277 patients with active AS (mean duration of disease: 10 years) who did not have complete spinal fusion
  • Patients were randomized to receive ENBREL 25 mg (n=138) or placebo (n=139) twice weekly for 24 weeks. NSAIDs and corticosteroids were allowed if doses remained stable for 2 weeks before the study start and throughout the study; 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 baseline
  • 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 domain
  • The 4 ASAS domains included patient global assessment measured on a 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 BASFI) measured on a VAS of “easy” to “impossible,” and inflammation (the average of 2 questions regarding morning stiffness on the 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 hours
  • 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 scale. During the course of this study, the official ASAS criteria were revised to eliminate the nocturnal pain assessment
    • One patient in the placebo group had a score of 0 at baseline and was not included in the analysis of % improvement in nocturnal pain assessment from baseline

Ankylosing Spondylitis Trial Reference:

  1. Data on file, Amgen; CSR 1637: December 20, 2002.

Moderate to Severe Polyarticular Juvenile Idiopathic Arthritis (JIA)

  • A two-part, multi-center study of 69 patients ages 4 to 17 years with moderate to severe polyarticular-course JIA who were refractory to or intolerant of MTX
  • In part 1, which was open-label, all patients received ENBREL 0.4 mg/kg subcutaneously twice weekly for 90 days
  • Responders (n=51), measured using the JIA definition of improvement defined as JIA 30, continued into part 2, the double-blind portion, and were randomized to receive either ENBREL (n=25) or placebo (n=26) for 4 months or until disease flare occurred
  • The primary efficacy endpoint was the number of patients with disease flare after ENBREL or placebo in part 2
  • At the conclusion of the 7-month trial, 58 of the original 69 patients (from the nonresponder, ENBREL, and placebo groups) were enrolled in a new unblinded, open-label follow-up using ENBREL 0.4 mg/kg twice weekly
  • Pediatric patients received long-term, open-label treatment with a 0.8-mg/kg weekly subcutaneous dose of ENBREL (up to a maximum of 50 mg per week)
  • Concurrent use of NSAIDs, corticosteroids, and/or MTX was permitted during the open-label extension phase
  •  

    Definition1,2

    The definition of improvement used to assess disease response had 6 response variables: global assessment of the severity of disease by the physician, global assessment of overall well-being by the patient or parent, number of “active” joints, number of joints with limitation of motion (LOM), functional ability (CHAQ), and erythrocyte sedimentation rate (ESR). Number of joints with LOM was counted only if LOM was accompanied by pain and/or tenderness.2


    JIA 30 response is defined as a ≥30% improvement in at least 3 of the 6 criteria of a modified JIA core set, with no more than 1 of 6 criteria worsening by more than 30%.2


    JIA 50 and 70 responses are defined as a ≥50% or ≥70% improvement, respectively, in at least 3 of 6 response criteria, with no more than 1 criterion worsening by more than 30%.2


    Disease flare was defined as a ≥30% worsening in 3 of the 6, a ≥30% improvement in not more than 1 of the 6 JIA core set criteria, and a minimum of 2 active joints.1

JIA Trial References

  1. Data on File, Amgen; 1618 LRA 10 yr: September 2008.
  2. Lovell DJ, Giannini EH, Reiff A, et al; for the Pediatric Rheumatology Collaborative Study Group. Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med. 2000;342:763-769.

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.

Reference

  1. Data on file, Amgen. Enbrel RA Clinical Trials Experience, 2012.

IMPORTANT SAFETY INFORMATION AND INDICATIONS: SERIOUS INFECTIONS

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

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

 

MALIGNANCIES

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

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

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

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

Pediatric Patients

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

NEUROLOGIC REACTIONS

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

CONGESTIVE HEART FAILURE

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

HEMATOLOGIC REACTIONS

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

HEPATITIS B REACTIVATION

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

ALLERGIC REACTIONS

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

IMMUNIZATIONS

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

AUTOIMMUNITY

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

WEGENER’S GRANULOMATOSIS PATIENTS

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

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

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

ADVERSE REACTIONS

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

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

DRUG INTERACTIONS

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

 

Please see Prescribing Information and Medication Guide.

 

INDICATIONS

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

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

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

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

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

Prescription Enbrel® (etanercept) is administered by injection.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

SERIOUS INFECTIONS

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

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

 

MALIGNANCIES

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

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

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

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

Pediatric Patients

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

NEUROLOGIC REACTIONS

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

CONGESTIVE HEART FAILURE

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

HEMATOLOGIC REACTIONS

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

HEPATITIS B REACTIVATION

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

ALLERGIC REACTIONS

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

IMMUNIZATIONS

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

AUTOIMMUNITY

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

WEGENER’S GRANULOMATOSIS PATIENTS

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

MODERATE TO SEVERE ALCOHOLIC HEPATITIS

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

ADVERSE REACTIONS

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

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

DRUG INTERACTIONS

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

 

Please see Prescribing Information and Medication Guide.

 

INDICATIONS

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

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

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

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

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