Overview

1
Overview

• Indications
• Psoriasis A Debilitating Disease
• Psoriasis An Immune-Mediated Disease
• ENBREL A New Approach to Psoriasis Management
• ENBREL Clinical Trials in Psoriasis
• Global Phase 3 Study
• U.S. Phase 3 Study Part 1
• U.S. Phase 3 Study Part 2 Discontinuation and
  Retreatment
• ENBREL Support Access, Enliven Services
  andDosing Practicalities
• Indications, Dosing, and Important Treatment
  Considerations

2
Psoriasis A Debilitating Disease
3
Epidemiology Who Suffers?

• 4.5 million to 7 million people in the US (men,
  women, and children) suffer from psoriasis1-3
• Between 2.1 and 2.6 of population2,4
• New cases between 150,000 and 260,000 per year2
• 30 of sufferers have moderate to severe disease2
• ?1.5 million people2
• Approximately 23 of psoriasis sufferers also
  have psoriatic arthritis2
• ?1 million people2
• Psoriasis typically precedes development of the
  arthritic component (70 before, 15 concurrent,
  15 after)5

References 1. Krueger G, et al. Arch Dermatol.
2001137280-284. 2. National Psoriasis
Foundation Web site. Available at
http//www.psoriasis.org/resources/statistics.
Accessed November 18, 2003. 3. National
Psoriasis Foundation survey. Available at
http//www.psoriasis.org/files. pdfs/pres/
npfsurvey.pdf. Accessed November 13, 2003. 4.
Koo J. Dermatol Clin. 199614485-496. 5.
Tankosic T, Sharma D. Psoriasis and Associate
Arthropathy. Waltham, ass Decision Resources,
Inc May 2001
4
Psoriasis

• Chronic, immune-mediated, inflammatory skin
  disease characterized by dry, thickened, scaling
  lesions1,2
• Associated with mild to severe disability3
• Associated with increased morbidity3,4
• Psoriatic arthritis
• Depression
• Anxiety
• Suicidal ideation

References 1. Choi J, et al. J Am Acad
Dermatol. 200349S57-S61. 2. Peters BP, et al.
Am J Health-Syst Pharm. 200057645-659. 3.
National Psoriasis Foundation Web site. Available
at http//psoriasis.org/resources/statistics.
Accessed November 18, 2003. 4. Gupta MA, et
al.Br J Dermatol. 1998139846-850.
5
Psoriasis Can Impair Quality of Life

• Physical symptoms cause physical distress1
• Activities of daily life are affected1
• Sleep
• Sexual activities
• Using hands
• Walking
• Sitting/standing long periods
• Job performance is affected1

Reference 1. Krueger G. Arch Dermatol.
2001137280-284.
6
Psoriasis Can Impair Psychosocial Well-Being

• Self-consciousness and social embarrassment1
• Stigmatization (real or perceived)2
• Personal and work relationships disturbed2
• Decrease in sexual activity3
• Increased use of psychiatric services2
• Increased alcohol consumption2
• Suicidal ideation4

References 1. Koo J. Dermatol Clin.
199614485-496. 2. Ginsburg IH, et al. Int J
Dermatol. 199332587-591. 3. Gupta MA, et al.
Int J Dermatol. 199736259-262. 4. Gupta MA, et
al.Br J Dermatol. 1998139846-50.
7
Degrees of Plaque Psoriasis Severity
Mild
Moderate
Severe
Photographs provided by National Psoriasis
Foundation/USA, www.psoriasis.org.
8
Psoriasis Extent and Severity

• Body surface area (BSA) is the physical measure
  of the extent of psoriasis, but may be inaccurate
  in conveying actual disease severity1
• Palm of hand represents approximately 1 BSA2
• If measured by BSA, 70 of patients have mild
  disease (lt3 BSA)3
• If measured by BSA, 30 of patients have
  moderate to severe disease (gt3 BSA)3

Approximately 1 of the bodys surface
Photograph provided by National Psoriasis
Foundation/USA, www.psoriasis.org. References.
1. Krueger GG, et al. J Am Acad Dermatol.
200043281-285. 2. National Psoriasis Foundation
Web site. Available at http//www.psoriasis.org/f
acts.psoriasis. Accessed March 16, 2004. 3.
National Psoriasis Foundation Web site. Available
at http//psoriasis.org/resources/statistics.
Accessed November 18, 2003.
9
PASI Score Calculation1
Reference 1. Fredricksson T, et al.
Dermatologica. 1978157238-244.
10
Psoriasis A Chronic Immune-Mediated
Inflammatory Disease
11
Evidence for the Role of TNFin Psoriasis

• TNF production is increased in psoriasis
• Elevated serum TNF levels1
• Elevated TNF levels in psoriatic plaque2,3
• TNF levels correlate strongly withdisease
  severity (PASI score)1,2
• TNF levels decrease with effective treatment1,3
• Extent of reduction correlates with clinical
  response

References. 1. Mussi A, et al. J Biol Regul
Homeost Agents. 199711115-118. 2. Bonifati C,
et al. Clin Exp Dermatol. 199419383-387. 3.
Ameglio F, et al. Dermatology. 1994189359-363.
12
Effects of TNF in Psoriasis1-4

1. TNF can facilitate T cell interactions with
   antigen-presenting cells

T cell activation
T cells infiltrate the dermis and epidermis

1. Adhesion molecules in the endothelium enable T
   cell infiltration

TNF
Cross section of psoriatic skin
Inflammation and keratinocyte hyperproliferation

1. T cells and keratinocytes release proinflammatory
   cytokines

References 1. Girolomoni G, et al. Curr Opin
Invest Drug. 200231590-1595. 2. Bonifati C, et
al. Int J Dermatol.199938241-251. 3. Krueger
JG, et al. J Am Acad Dermatol. 2002461-23. 4.
Nickoloff BJ. Arch Dermatol. 19991351104-1110.
13
Etanercept A New Approach to Psoriasis Management
14
ENBREL Indications for Psoriatic Disease1,2

• ENBREL is the only treatment indicated for both
  plaque psoriasis and psoriatic arthritis
• ENBREL is indicated for the treatment of adult
  patients (18 years or older) with chronic
  moderate to severe plaque psoriasis who are
  candidates for systemic therapy or phototherapy
• ENBREL is indicated for reducing signs and
  symptoms and inhibiting the progression of
  structural damage of active arthritis in patients
  with psoriatic arthritis. ENBREL can be used in
  combination with methotrexate in patients who do
  not respond adequately to methotrexate alone

Reference 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif.
15
ENBREL is the Only Fully HumanTNF Receptor1

• ENBREL is not amonoclonal antibody
• Low immunogenicity no neutralizing antibodies
• ENBREL binds specificallyto TNF and blocks its
  interaction with cell surface TNF receptors

Reference 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif.
16
ENBREL Mimics Natural TNF Inhibition to Control
Inflammation1

• ENBREL is a soluble TNF receptor that
  competitively binds to soluble TNF to prevent
  activation of cell-surface receptors

TNF initiates inflammation
ENBREL bound tocirculating TNF
Cell-surface receptors are not activatedby TNF
Reference 1. Data on file, Amgen/Wyeth, Thousand
Oaks, CA.
17
ENBREL Clinical Trials in Psoriasis
18
Baseline Disease Characteristics Across Global
and US Study Groups1
N 1283
Psoriasis BSA involvement (median ) 21.3
Baseline PASI Score (median) 15.9
DSGA of Psoriasis
Moderate Severe (3-5) 84
Prior Systemic Therapies
Systemic Agent 67
Phototherapy 59
Systemic or Phototherapy 82
Dermatologist Static Global Assessment of
Psoriasis Reference 1. Data on file, Amgen,
Thousand Oaks, Calif.
19
Global Phase 3 Study
20
Global Phase 3 Study Design1

• Subjects and site personnel remained blinded to
  original treatment group through 3 months
• No analysis was performed until all subjects
  completed 6 months

Screen and Washout
50 mg twice weekly
50 mg weekly (25 mg BIW)
50 mg weekly (25 mg BIW)
Placebo
3 Months (Primary Endpoint)
Day 1
6 Months
N 611
Reference 1. Data on file, Amgen, Thousand Oaks,
Calif.
21
Inclusion and Exclusion Criteria1
Global Phase 3 Study

• Inclusion
• Active but clinically stable plaque psoriasis
  involving gt10 BSA
• Minimal screening PASI score of 10 (moderate to
  severe psoriasis)
• Must have received previous phototherapy or
  systemic therapyat least once or have been an
  appropriate candidate for therapy
• At least 18 years of age

• Exclusion
• Patients with guttate, erythrodermic, or pustular
  psoriasis or other active skin conditions at
  screening that would interfere with evaluation
• Previous use of ENBREL or antibodies to TNF
• Antibiotics within the previous week
• Topical steroids, topical vitamin A or D analog
  preparations, anthralin, or UVB within previous 2
  weeks of study drug initiation
• Treatment with biologic or investigational drugs,
  PUVA phototherapy, systemic corticosteroids, or
  systemic psoriasis therapy within 4 weeks of
  study drug initiation
• Anti-CD4 or diphtheria IL-2 fusion proteinwithin
  previous 6 months

Reference 1. Data on file, Amgen, Thousand
Oaks, Calif.
22
Similar Baseline Demographics/Clinical
Characteristics Across Groups1
Global Phase 3 Study Part 1
Placebo 50 Mg Twice Weekly
Patient number 193 194
Age (mean, yrs) 45 45
Male 64 67
Caucasian 91 89
Weight (mean, kg) 91 86
BSA involvement 27 29
Psoriasis duration (yrs) 19 20
PASI 18.6 19.5
Patient global score of 4 or 5 (05 scale) 71 70
Reference 1. Data on file, Amgen, Thousand
Oaks, Calif.
23
Patients with PASI Responseat 3 months1
Global Phase 3 Study


Plt0.0001 vs placebo

ENBREL 50 mg weekly (25 mg BIW) was also studied
in this trial. Reference 1. Enbrel Prescribing
Information, Immunex Corporation, Thousand Oaks,
Calif.
24
PASI 75 Response Was Maintained Following
Step-Down Dosing1
Global Phase 3 Study
Placebo ENBREL 50 mg twice weekly ENBREL 50 mg
weekly (25 mg BIW)
Plt0.001 vs placebo Plt0.0001 vs placebo
50 mg weekly (25 mg BIW)
50

of Patients

25

Modified ITT analysis ENBREL 50 mg weekly (25 mg
BIW) was also studied in this trial. Reference
1. Enbrel Prescribing Information, Immunex
Corporation, Thousand Oaks, Calif.
25
Global Phase 3 Summary ENBREL Step-Down Dosing
Maintained Response1,2

• In patients treated with 50 mg twice weeklyfor 3
  months, followed by step-down dosing to 50 mg
  weekly
• PASI 75 response rate continued to increase,
  reaching 50 by 6 months
• 77 of week 12 PASI 75 responders maintained
  their response through 6 months
• An additional 32 of week 12 nonresponders
  achieved a PASI 75 by 6 months
• ENBREL was generally well tolerated

References 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif. 2.
Data on file, Amgen, Thousand Oaks, Calif.
26
Global Phase 3 StudyPatient 23651
Baseline
Week 2
3 months
6 months
57.3
15.5
6.0
5.7
PASIScore
73
89
90
PASI Improvement
Patient was initially treated with ENBREL 50 mg
twice weekly and was steppeddown to 50 mg weekly
(25 mg BIW) at 3 months. Reference 1. Data on
file, Amgen, Thousand Oaks, Calif.
27
Global Phase 3 StudyPatient 23651
Patient was initially treated with ENBREL 50 mg
twice weekly and was stepped down to 50 mg weekly
(25 mg BIW) at 3 months. Reference 1. Data on
file, Amgen, Thousand Oaks, Calif.
28
Global Phase 3 StudyPatient 30661
Patient was initially treated with ENBREL 50 mg
twice weekly and was stepped down to 50 mg weekly
(25 mg BIW) at 3 months. Reference 1. Data on
file, Amgen, Thousand Oaks, Calif.
29
Global Phase 3 StudyPatient 30551
Patient was initially treated with ENBREL 50 mg
twice weekly and was stepped down to 50 mg weekly
(25 mg BIW) at 3 months. Reference 1. Data on
file, Amgen, Thousand Oaks, Calif.
30
U.S. Phase 3 Study of ENBREL in Psoriasis
31
ENBREL in Psoriasis Study Design1,2

• No analysis was performed until all subjects
  completed 15 months

Efficacy Evaluation U.S. Phase 3 Study Part 1
Safety Evaluation U.S. Phase 3 Study Part 2
Discontinuation Retreatment
Double Blind
50 mg twice weekly

50 mg
Twice Weekly
50 mg weekly (25 mg BIW)
Weekly (25 mg B/W)
Discontinue Drug
PASI ?50

50 mg
25 mg once weekly

Once Weekly
25 mg
Blinded retreatment with 6 month dose at time of
loss of response
50 mgWeekly (125 mg B/W)


Placebo
PASI lt50
50 mg weekly (25 mg BIW)
3 months
Day 1
6 months
Assess responder status
Primary Endpoint
References 1. Leonardi CL, et al. N Engl J Med.
20033492012-2020.2. Data on file, Amgen,
Thousand Oaks, Calif.
32
Similar Baseline Demographics/Clinical
Characteristics Across Groups1
US Phase 3 Study
Placebo 50 Mg Twice Weekly
Patient number 166 164
Age (mean, yrs) 46 45
Male 63 65
Caucasian 90 87
Weight (mean, kg) 96 95
BSA involvement 28.8 29.9
Psoriasis duration (yrs) 18 19
PASI 18.3 18.5
Patient global score of 4 or 5 (05 scale) 76 76
Reference 1. Data on file, Amgen, Thousand
Oaks, Calif.
33
PASI 75 Responses Were Similar at 6 Months
in Both Phase 3 Studies1
Placebo
ENBREL 50 mg twice weekly
ENBREL 50 mg weekly (25 mg BIW)
Global Study (N 611)
U.S. Study (N 672)
Reference 1. Data on file, Amgen, Thousand Oaks,
Calif.
34
Response May Be Seen As Early As 1 Month1,2
Placebo
U.S. Phase 3 Study
ENBREL 50 mg twice weekly
ENBREL 50 mg weekly (25 mg BIW)
ENBREL 50 mg weekly (25 mg BIW) and Enbrel 25 mg
once weekly were also studied in this
trial. Reference 1. Enbrel Prescribing
Information, Immunex Corporation, Thousand Oaks,
Calif. 2. Data on file, Amgen, Thousand
Oaks, Calif.
35
Only Injection Site Reactions were Significant
Through Week 241
U.S. Phase 3 Study Part 1 Adverse events and
infections occurring in ?5 of patients
Placebo/ENBREL week 1-12 week 12-24 Placebo/ENBREL week 1-12 week 12-24 ENBREL week 1-24 ENBREL week 1-24
Placebo 25 mg twice weekly 25 mg twice weekly 50 mg twice weekly
Injection site reaction 7 7 33 26
Headache 7 5 12 9
Upper respiratory Infection 11 6 14 12
Asthenia 3 1 7 3
Myalgia 2 2 7 4
Accidental injury 4 4 7 7
Sinusitis 1 1 6 5
Nausea 1 1 3 3
Injection site bruising 4 2 3 5
Rash 2 0 4 6
Reference 1. Leonardi CL, Powers JL, Matheson
RT, et al. Etanercept as monotherapy in patients
with psoriasis. N Engl J Med. 20033492012-2020.
36
Week 24 Tolerability
U.S. Phase 3 Study Part 1

• Grade 3 serious adverse events (SAEs) and
  infections were well balanced across active
  treatment groups1
• Serious adverse events and serious infections
  were minimal1,2
• No cases of TB or opportunistic infections
  reported1,2

Placebo/25 mg twice weekly 25 mg once weekly 25 mg twice weekly 50 mg twice weekly
Noninfectious SAEs 5 6 6 5
Infectious SAEs 3 2 0 1
References 1. Leonardi CL, Powers JL, Matheson
RT, et al. Etanercept as monotherapy in patients
with psoriasis. N Engl J Med. 20033492012-2020.
2. Data on file, Amgen, Thousand Oaks, Calif.
37
ENBREL U.S. Phase 3 StudyPatient 16611
Baseline
3 months
6 months
22.7
6.3
3.8
PASIScore
72
83
PASI Improvement
Patient was treated with Enbrel 25 mg once weekly
through 6 months. Reference 1. Data on file,
Amgen, Thousand Oaks, Calif.
38
ENBREL U.S. Phase 3 StudyPatient 16671
Baseline
3 months
6 months
28.4
22.0
1.2
PASIScore
23
96
PASI Improvement
Patient initially received placebo, and was then
switched to ENBREL 50 mg weekly (25 mg BIW) at 3
months. Reference 1. Data on file,
Amgen, Thousand Oaks, Calif.
39
U.S. Phase 3 Study Clinical Response Was Rapid,
Consistent, and Sustained1

• A statistically significant improvement in the
  percentage of patients achieving a PASI 75
  response was seen as early as 1 month with the 50
  mg twice-weekly dose
• Continued improvement was seen through 6 months
• PASI 75 reached 47 at 12 weeks and 54 at 6
  months in the 50 mg twice-weekly group
• Week 24 PASI 75 response rates in the global
  study were similar to those reported in the U.S.
  study, in which patients were treated with 50 mg
  twice weekly throughout the 6-month period

Reference 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif.
40
U.S. Phase 3 Study ENBREL Was Generally Well
Tolerated1

• ENBREL had similar rates of adverse events and
  infections in all treatment groups
• Adverse events and infections comparable to
  placeboat 3 months
• Injection site reactions slightly higher in
  active dose groupsat 3 months
• Safety and adverse event profile was
  unremarkableover 6 months of dosing
• Safety and adverse event profile was similar
  among all treatment arms and comparable to the
  global study

Reference 1. Leonardi CL, et al. N Engl J Med.
20033492012-2020.
41
Discontinuation and Retreatment Safety
EvaluationU.S. Phase 3 Study Part 2
42
Time-to-Loss of Response Analysis
Etanercept US Phase 3 Study
Double Blind Period
Drug Discontinuation Period
Discontinue drug and follow monthly until loss
of response Loss of response Loss of half of
the PASI improvement achieved between baseline
and week 24
50 mg twice weekly
PASI ?50
50 mg weekly (25 mg BIW)
N 409
25 mg once weekly
50 mg weekly
Placebo
Example Baseline PASI 20 Week 24 PASI
5 Improvement 15 (75) Relapse PASI 12.5
3 months
6 months
Day 1
Primary Endpoint
43
Time to Loss of Response Following ENBREL
Discontinuation Was Approximately 3 Months1
U.S. Phase 3 Study Part 2
Dose DuringDouble-Blind Period Median Time toLoss of Response After Discontinuation (Days) N
Placebo/50 mg weekly(25 mg BIW) 85 95
50 mg BIW 91 122
Total 85 409
Defined as loss of gt50 of improvement in PASI
score in patients who hadpreviously achieved a
PASI 50 response. Reference 1. Data on file,
Amgen, Thousand Oaks, Calif.
44
Rebound NPF Medical Advisory Board Definition1
We operationally define rebound as a PASI of
125or greater of baseline or new generalized
pustular, erythrodermic, or more inflammatory
psoriasis occurring within 3 months of stopping
therapy.
Reference 1. Gordon KB, et al. NPF Psoriasis
Forum. 20028(3)1-3.
45
No Rebound Occurred at 50 mgTwice Weekly or 25
mg Twice Weekly1
U.S. Phase 3 Study Part 2

• In 409 patients observed during the
  discontinuation period
• No conversion of morphology
• No SAEs or hospitalization due to psoriasis
• No study discontinuation due to psoriasis AEs
• One case of rebound (0.2) was reported in the 25
  mg once-weekly dosing arm.

ENBREL 25 mg once weekly dosing and twice weekly
dosing were also studied in this
trial. Reference 1. Data on file, Amgen,
Thousand Oaks, Calif.
46
Initial Treatment and Retreatment With ENBREL
Resulted in Similar PASI 75 Response Rates1,2

• After 3 months of retreatment after
  discontinuation, 93 of the PASI 75 responders at
  month 3 achieved a PASI 50 response

References 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif. 2.
Data on file, Amgen, Thousand Oaks, Calif.
47
US Phase 3 Study Part 2Patient 1610
Baseline
Week 12
Week 24
Week 48
Week 60
21.4
3.6
3.6
10.4
14.4
PASIScore
83.2
83.2
51.4
32.7
PASI Improvement
Patient 1610 on 50 mg twice-weekly dosing
treatment arm.
48
US Phase 3 Study Part 2Patient 1665
Baseline
Week 12
Week 48
Week 60
Week 24
PASIScore
14.4
2.4
5.1
3.5
4.2
83.3
64.6
75.7
70.8
PASI Improvement
Patient 1610 on 50 mg BIW-dosing treatment arm
and over discontinuation period.
49
Phase 3 Study Part 2 Summary ENBREL Was
Effective and Generally Well Tolerated Over the
Discontinuation and Retreatment Period1

• No increase in adverse events despite increased
  dose
• No increase in adverse events over 15 months of
  therapy
• Rebound did not occur in the 50 mg weekly or 50
  mgtwice-weekly treatment arms
• In 409 patients observed during the
  discontinuation period
• No conversion of morphology
• No SAEs or hospitalization due to psoriasis
• No study discontinuation due to psoriasis AEs
• After 3 months of retreatment after
  discontinuation,93 of PASI 75 responders at
  month 3 achieved aPASI 50 response

Reference 1. Data on file, Amgen, Thousand
Oaks, Calif.
50
ENBREL in Psoriasis Conclusions
51
In Two Phase 3 Psoriasis Studies, ENBRELWas
Shown To Be Generally Well Tolerated1

• ENBREL has exhibited a consistent safety profile
• No increase in adverse events despite increased
  dose or step-down in dose
• No increase in adverse events over 15 months(60
  weeks) of therapy
• ENBREL was generally well tolerated during
  discontinuation and retreatment
• No rebound seen in the 50 mg weekly or 50 mg
  BIWtreatment arms

Reference 1. Data on file, Amgen, Thousand
Oaks, Calif.
52
In Two Phase 3 Psoriasis Studies, ENBREL
Demonstrated Rapid and Consistent Efficacy1

• ENBREL has shown consistent andsustainable
  efficacy
• Efficacy consistent across all endpoints in both
  psoriasis studies
• At 6 months, efficacy with step-down dosingwas
  similar to that reported with 50 mg twice-weekly
  dosing
• ENBREL can be stopped and restarted with
  comparable efficacy reestablished

Reference 1. Data on file, Amgen, Thousand
Oaks, Calif.
53
ENBREL Support Access, Enliven Services, and
Dosing Practicalities
54
Dermatology Access Options for Enbrel
Dermatologist decides to Rx ENBREL (etanercept)
and has 3 options
Amgen PSR/DSR provides messages, collateral,
options, follow-up
Rx to Patient (business as usual)
Office/Patient calls 1-888-4ENBREL for questions
Physician calls/faxes Specialty Rx directly

• Simple options will help ENBREL prescriptions to
  be filled promptly
• Your office will receive a call only if
  additional documentation is needed

55
Enliven Services Support for Health Care
Professionals Who Use ENBREL

• Enliven Services is the
• centralized resource for
• Physician/office staff
• Pharmacists
• One number for health care professionals
  1-888-4ENBREL (1-888-436-2735)
• www.enbrel.com also offers access to Enliven
  services

Teaching Kits for Dosing and Administration
56
Teaching Kit A Resource for Health Care
Professionals

• Components Include
• Guide for teaching patients how to use ENBREL
• Getting Patients Started on ENBREL Brochure
• Cap removal tool
• Instructional video

57
Enliven Services Extensive Resources for
Patients
PatientResource Kits

• Enliven Services support includes
• Free educational resources for patients
• Newsletters, free sharps containers, free travel
  coolers, and more for patients
• Patients enrolled in Enliven have shown a higher
  persistency with therapy than those not enrolled
  and compliance may be improved
• Registered Nurses
• 8 am to 11 pm EST, 7 days a week
• Insurance Specialists
• Spanish-speaking representatives
• One number for patients
• 1-888-4ENBREL (I-888-436-2735)or www.enbrel.com

Patient Brochures
Travel Coolers
Sharps Containers
Psoriasis
Newsletters
58
Resource Kit for Patients Using Etanercept

• Components include
• Instruction video
• Handbook with step-by-step instruction guide
• Sharps container
• Cap removal tool
• Table mat

59
Mixing Station

• Developed to help prepare a dose of etanercept
• Helps patient remove vial cap, remove needle
  cover, reconstitute etanercept, and fill syringe
  for injection

New
60
Etanercept Drug Preparation

• Reconstitute aseptically with 1 mL of supplied
  Sterile Bacteriostatic Water for Injection, USP
  (0.9 benzyl alcohol)
• Do not reconstitute ENBREL with other diluents
• A vial adapter is supplied for use when
  reconstituting ENBREL
• 25-gauge needle should not be used if multiple
  doses are going to be withdrawn from the vial

61
Etanercept Drug Preparation

• Inject diluent slowly
• DONT SHAKE

Some normal foaming will occur Swirl gently to
dissolve Dissolution time lt10 minutes
62
Etanercept Drug Preparation

• Visually inspect for particulate matter
  anddiscoloration before administration
• Reconstituted solution should be clear and
  colorless
• Do not use if discolored or cloudy
• Do not use if particulatematter remains
• Use within 6 hoursunless refrigerated

63
Etanercept Storage

• Do not use beyond date stamped on carton or
  labels
• Reconstituted etanercept can be stored up to 14
  days between 2C and 8C (36F - 46F)
• Maintains protein stability
• Do not freeze

64
Etanercept Administration Injection

• Rotate injection sites (thigh, abdomen,upper
  arm) after each injection
• New injections at least 1 inch from old site
• Never inject where skin is tender, bruised, red,
  or hard

65
Injection Site Reactions

• Rare
• Occur in approximately 14 of psoriasis patients
• Mild to moderate in intensity
• Occur early in therapy and usually last about 3
  days
• Incidence decreases withcontinued
  administrationpast 1 month

66
Managing Injection Site Reactions

• How to minimize
• Prepare site properly
• Inject into fatty areas of legs and arms
• Rotate sites
• Avoid injecting in swollen, hard, or red areas
• Treatment is generally not necessary
• Other supportive treatments
• Cold compress
• Oral antihistamines
• Topical corticosteroid creams

67
Role of the Dermatology Staff

• Management of patient apprehension and concerns
• Encouragement provided by nurse education and
  support
• Involvement of caregivers, family members
• Take time for demonstration or discussion
• Confirm patient comfort level
• Provide ongoing support
• Physician, staff
• Company
• Materials
• Caregivers, family members

68
ENBREL Indications and Important Treatment
Considerations
69
ENBREL Indications

• ENBREL is indicated for the treatment of adult
  patients (18 years or older) with chronic
  moderate to severe plaque psoriasis who are
  candidates for systemic therapy or phototherapy1
• ENBREL is indicated for reducing signs and
  symptoms and inhibiting the progression of
  structural damage of active arthritis in patients
  with psoriatic arthritis. ENBREL can be used in
  combination with methotrexate in patients who do
  not respond adequately to methotrexate alone1

References 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif.
70
ENBREL Indications1

• ENBREL is indicated for reducing signs and
  symptoms of moderately to severely active
  polyarticular-course juvenile rheumatoid
  arthritis in patients 4 years of age and older
  who have had an inadequate response to one or
  more DMARDs
• ENBREL is indicated for reducing signs and
  symptoms, inhibiting the progression of
  structural damage, and improving physical
  function in patients with moderately to severely
  active rheumatoid arthritis. ENBREL can be used
  in combination with methotrexate in patients who
  do not respond adequately to methotrexate alone
• ENBREL is indicated for reducing signs and
  symptoms in patients with active ankylosing
  spondylitis

Reference 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif.
71
ENBREL Administration1

• The recommended starting dose of ENBREL for adult
  patients with psoriasis is a 50-mg subcutaneous
  (SC) dose given twice weekly (administered 3 to 4
  days apart) for 12 weeks followed by a reduction
  to a maintenance dose of 50 mg weekly
• For adult patients with psoriatic arthritis, the
  dosing of ENBREL is as follows
• Once weekly two SC injections of 25-mg each on
  the same day, or
• Twice weekly 25-mg SC injection, administered3
  or 4 days apart
• SC injection can be easy to learn and allows
  convenient at-home self-administration after
  proper instruction
• ENBREL is supplied in 25-mg vials for
  reconstitution

Reference 1. Enbrel Prescribing Information,
Immunex Corporation, Thousand Oaks, Calif.
72
Important Treatment Considerations

• IN POSTMARKETING USE, THE FOLLOWING SERIOUS
  ADVERSE
• EVENTS HAVE BEEN REPORTED
• SERIOUS INFECTIONS AND SEPSIS, INCLUDING
  FATALITIES
• MANY OF THESE INFECTIONS OCCURRED IN PATIENTS
  PREDISPOSED TO INFECTIONS BECAUSE OF CONCOMITANT
  IMMUNOSUPPRESSIVE THERAPY AND/OR THEIR UNDERLYING
  DISEASE
• RARE CASES OF TB HAVE BEEN OBSERVED
• DISCONTINUE ENBREL IN PATIENTS WITH SERIOUS
  INFECTIONS OR SEPSIS

73
Important Treatment Considerations (contd)

• DO NOT START ENBREL IN THE PRESENCE OF SEPSIS,
  INFECTION (INCLUDING CHRONIC OR LOCALIZED), OR
  ALLERGY TO ENBREL OR ITS COMPONENTS
• USE CAUTION IN PATIENTS PREDISPOSED TO INFECTION,
  SUCH AS THOSE WITH ADVANCED OR POORLY CONTROLLED
  DIABETES
• Cases of CNS demyelinating disorders (some
  presenting with mental status changes and some
  associated with permanent disability), transverse
  myelitis, optic neuritis, multiple sclerosis, and
  new onset or exacerbation of seizure disorder
• The causal relationship to ENBREL therapy is
  unclear
• Exercise caution when considering ENBREL for
  patients with these disorders

74
Important Treatment Considerations (contd)

• Rare cases of pancytopenia, including aplastic
  anemia, some fatal
• The causal relationship to ENBREL (etanercept)
  therapy is unclear
• Exercise caution 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
• In clinical trials of all TNF inhibitors, a
  higher rate of lymphoma was seen compared to the
  general population however, the risk of lymphoma
  may be up to several-fold higher in RA patients
• The role of TNF inhibitors in the development of
  lymphoma is unknown
• In clinical trials, the incidence of malignancies
  other than lymphoma has not increased with
  exposure to ENBREL and is similar to the
  projected background rate

75
Important Treatment Considerations (contd)
Most Frequently Reported Adverse Events in RA
Clinical Trials
Percentage of Patients Percentage of Patients Percentage of Patients Percentage of Patients
Placebo Controlled Placebo Controlled Active Controlled Active Controlled
Event Placebo(n 152) ENBREL(n 349) MTX (n 217) ENBREL (n 415)
Injection site reactions 10 37 7 34
Infection (total) Nonupper respiratory Upper respiratory 32 32 16 35 38 29 72 60 39 64 51 31
Headache 13 17 27 24
The 3 most commonly reported adverse events
includes data from a 6-month study in which
patients received concurrent MTX therapy. The
duration of exposure for patients receiving
placebo was less than that for the patients
treated with ENBREL (etanercept). MTX
patients received concomitant placebo
injections. Infection (total) includes data
from 3 placebo-controlled trials. Nonupper
respiratory and upper respiratory include data
only from the 2 placebo-controlled trials where
infections were collected separately from adverse
events (placebo n 110, ENBREL n 213).
76
Important Treatment Considerations (contd)

• Adverse events in the AS and psoriatic arthritis
  trials were similar to those reported in RA
  clinical trials
• No increased incidence of tuberculosis (TB)
  observed in clinical trials however, rare cases
  of TB have been observed in postmarketing use
• Routine laboratory monitoring specific for
  ENBREL (etanercept) therapy not required
  careful medical management and supervision of
  patients recommended

77
Important Treatment Considerations (contd)

• In a JRA study (n 69), infections (62),
  headache (19), abdominal pain (19), vomiting
  (13), and nausea (9) occurred more frequently
  than in adults. The types of infections reported
  in JRA patients were generally mild and
  consistent with those commonly seen in outpatient
  pediatric populations
• Serious adverse reactions reported rarely in a
  JRA study were varicella (3), gastroenteritis
  (3), depression/personality disorder (1),
  cutaneous ulcer (1), esophagitis/gastritis (1),
  group A streptococcal septic shock (1), type I
  diabetes mellitus (1), and soft tissue and
  postoperative wound infection (1)
• Please see full Prescribing Information

78
ENBREL in the Treatment of Psoriasis