This document describes a 5-year observational study to assess the long-term safety and effectiveness of etanercept (Enbrel) for the treatment of plaque psoriasis. The study will involve 2500 patients across 375 sites in the US and Canada. Patients will receive etanercept treatment determined by their physician and be evaluated every 6 months for 5 years. The primary objectives are to determine incidence rates of serious adverse events, serious infections, and malignancies. Secondary objectives include evaluating effectiveness outcomes using measures like Psoriasis Area and Severity Index. Data will be analyzed using descriptive statistics and Kaplan-Meier methodology.

1. Reference: Public Document NCT #: NCT00322439
Sponsor: Amgen Canada Inc.
By: Vivette Escueta, RPh
Presented at AAPS, 2015
Research Director: Professor Peivand Pirouzi

2. I. Introduction
II. Study Objectives and
Endpoints
III. Study Design
IV. Study Population
V. Study Treatment and
Duration
VI. Study Procedures
VII. Data Analysis
VIII. Data Collection and
Management
IX. Adverse Event Reporting
X. Strengths and Limitations
XI. Quality Control and
Quality Assurance
XII. Ethics
XIII. Communication and
Publication of Study
XIV. References

3.  ETANERCEPT
 Medical Biologic Device
 Amgen Canada
 Enbrel
 TNF Blocker
 Indicated for Chronic
Moderate to Severe Plaque
Psoriasis
 Relieve the symptoms of
autoimmune disorders

4.  ETANERCEPT
 Medical Biologic Device
 Amgen Canada
 Enbrel
 TNF Blocker
 Indicated for Chronic
Moderate to Severe Plaque
Psoriasis
 Relieve the symptoms of
autoimmune disorders
 First approved for RA
(USA, 1998)
 Approval 2004 (US) and
2005 (Canada)
 Administered SQ
 Pre-filled syringe
 Pre-filled autoinjector
 Multiple-use Vial

5.  The study is a long-term analysis of Safety
 5 years observational and surveillance registry
 2500 patients assessments across research sites in US
and CANADA
 Needed to detect rare adverse events in a broader
patient population
 Malignancies, Lymphomas, Nonmelanoma Skin Cancer
(NMSC)

6.  To Assess the long-term safety and effectiveness of
Etanercept (Enbrel)
 Determine incidence rates of SAE and SIE
 Compare Rates of SAE, SIE and EMIs according to:
 Prior exposure to systemic therapies or phototherapy
 Exposure to Enbrel therapy
 Presence of certain co-morbid disorders
 Evaluate incidence rate of EMIs for participating subjects
 Evaluate Effectiveness outcomes

7.  Phase IV, Prospective, Multicenter, Observational,
Surveillance registry
 Self-administered dose of etanercept
 Evaluated at 6-months interval for 5 years.

8. Inclusion Criteria
 Patients with Plaque
Psoriasis
 On Enbrel therapy
 Prior exposure to any TNF
Inhibitor
 Patients for whom Enbrel
is contraindicated
 Patients currently enrolled
in or has not yet completed
at least 30 days since
ending their
investigational drug study
Exclusion Criteria

9.  Participants receive etanercept treatment at the dose
and regimen determined by the investigator
 Evaluated every 6 months for 5 years
 Participants may:
 discontinue therapy
 Switch to another anti-psoriatic therapies
 Discontinue any or all treatments

10.  375 sites (37 Canada, 338 USA)
 2500 Patients
 Assessment of SAE, SIE and EMI throughout the study and 30 days
after.
 SPGA at baseline, year 3 and year 5
 DLQI at Baseline, Year 3 and Year 5
 EQ-5D at baseline, Year 3 and Year 5
 BSA at baseline Year 3 and Year 5
 Incidence proportions for SAE, SIE and EMIs collected from a large US
administrative health claim database
 Truven Health MarketScan Commercial Claims and Encounters and
MarketScan Medicare Supplemental Database

11.  MarketScan collect enrollment data, medical claims and lab and
prescription data.
 Criteria:
 18 years or older and 90 years or younger
 Between January 1, 2006 to December 31, 2006 (enrollment period)
 12 months of continuous enrollment before their index date to
describe their medical and treatment history (baseline period)
 Incidence rates calculated and age-and sex-standardized to the
study population for each outcome of interest at 95% confidence
intervals.

12.  Descriptive Statistics for baseline characteristics and
outcome measures
 Kaplan-Meier Methodology for primary analysis of
safety end points
 Cumulative Incidences: 2 methods:
 Include all time from first dose of etanercept to start
date of the first event occurrence
 Excluding time intervals and corresponding events
when patient is not exposed

13.  Adverse events will be collected from scheduled visits
 Telephone reminders for visits
 Retention packages
 Reimbursements for each site for the effort to remind
patients
 In case of patient transfers
 Telephone calls
 Telephone visits

14.  Use of Large database
 MarketScan registered 48,136 Psoriasis patients
 Lack of internal comparator
 Rare events may not be detected

15.  The Sponsor will not have access to health register records
at the level of the individual patient
 Investigators are responsible for following site standard
protocol to ensure data quality and integrity,
 including archiving of statistical programs,
 documentation of data cleaning
 validity for created variables,
 description of available data.
 Records will be retained on each site however all copies of
the data and results will be made available to the sponsor.

16.  In compliance with the Declaration of Helsinki
 Follow Good Pharmacoepidemiology Practice, Good
Clinical Practice, Good Epidemiological Practice
 Informed Consents and Protocol approval from IRB
 All patients provided with IC prior
conducting/participating in study.

17.  American Academy of Dermatology Work Group, Menter, A., Korman, N.J., Elmets, C.A.,
Feldman, S.R., Gelfand, J.M., Gordon, K.B. et al. Guidelines of care for the
management of psoriasis and psoriatic arthritis, section 6. Guidelines of care for
the treatment of psoriasis and psoriatic arthritis: case-based presentations and
evidence-based conclusions. J Am Acad Dermatol. 2011; 65: 137–174
 Enbrel (etanercept) [full prescribing information]. Immunex Corp, Thousand Oaks,
CA; 2011
 Kimball, A.B., Pariser, D., Yamauchi, P.S., Menter, A., Teller, C.F., Shi, Y. et al. OBSERVE-
5, an observational post-marketing safety surveillance registry of etanercept for
the treatment of psoriasis: a model for studying new psoriasis therapies. Psoriasis
Forum. 2010; 16: 3–7
 Kimball, A.B., Pariser, D., Yamauchi, P.S., Menter, A., Teller, C.F., Shi, Y. et al. OBSERVE-5
interim analysis: an observational postmarketing safety registry of etanercept for
the treatment of psoriasis.J Am Acad Dermatol. 2013; 68: 756–764