Reference: Public Document NCT #: NCT00322439

Sponsor: Amgen Canada Inc.

By: Vivette Escueta, RPh

Presented at AAPS, 2015

Research Director: Professor Peivand Pirouzi

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

ETANERCEPT Medical Biologic Device Amgen Canada Enbrel

TNF Blocker Indicated for Chronic

Moderate to Severe Plaque Psoriasis

Relieve the symptoms of autoimmune disorders

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

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)

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

Phase IV, Prospective, Multicenter, Observational, Surveillance registry

Self-administered dose of etanercept

Evaluated at 6-months interval for 5 years.

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

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

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

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.

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

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

Use of Large database MarketScan registered 48,136 Psoriasis patients

Lack of internal comparator

Rare events may not be detected

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.

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.

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