A PROSPECTIVE EVALUATION OF THE RADIOGRAPHIC EFFICACY OF ETANERCEPT IN PATIENTS WITH RHEUMATOID ARTHRITIS OR PSORIATIC ARTHRITIS.
Conditions: Rheumatoid Arthritis, Psoriasis Arthritis
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) DRUG STUDY PROTOCOL
A PROSPECTIVE EVALUATION OF THE RADIOGRAPHIC EFFICACY OF 
ETANERCEPT IN PATIENTS WITH RHEUMATOID ARTHRITIS OR PSORIATIC 
ARTHRITIS
Compound Number:
PF-05208752
Compound Name:
Etanercept
Study Number:
B1801317
Phase
IV
Version and Date:
Final Protocol
20 September 2011 

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TABLE OF CONTENTS
FIGURES ...................................................................................................................................3
1. INTRODUCTION .................................................................................................................5
1.1. Background and Rationale ...............................................................................................5
2. STUDY OBJECTIVES AND ENDPOINTS .........................................................................6
2.1. Endpoints ..........................................................................................................................6
2.1.1. Primary Endpoint: .......................................................................................................6
2.1.2. Secondary Endpoints:..................................................................................................6
3. STUDY DESIGN...................................................................................................................7
4. STUDY POPULATION ........................................................................................................7
4.1. Inclusion Criteria ..............................................................................................................7
4.2. Exclusion Criteria .............................................................................................................8
5. STUDY TREATMENT AND DURATION .........................................................................9
6. STUDY PROCEDURES .......................................................................................................9
6.1. Effectiveness criteria ......................................................................................................10
6.2. Safety criteria ..................................................................................................................11
6.3. Health Outcomes ............................................................................................................11
6.4. Optional (12 to 48 months prior to initation of Etanercept). ..........................................11
6.5. The required Baseline Visit ............................................................................................11
6.6. Study Period ...................................................................................................................12
6.6.1. Scheduled Visits 2-6 .................................................................................................12
6.6.2. Final (or close out) Visit 7/week 78 ..........................................................................13
6.7. Follow-up Visit ...............................................................................................................14
6.8. Subject Withdrawal ........................................................................................................14
6.9. Schedule of Activities .....................................................................................................15
7. DATA ANALYSIS/STATISTICAL METHODS ...............................................................17
7.1. Sample Size Calculation .................................................................................................17
7.2. Effectiveness Analysis ....................................................................................................17
7.3. Safety Analysis ...............................................................................................................18
7.4. Interim Analysis .............................................................................................................18
7.4.1. First Interim analysis .................................................................................................18
7.4.2. Second Interim Analysis ...........................................................................................19
8. DATA COLLECTION AND DATA MANAGEMENT .....................................................19
8.1. Case Report Forms (CRFs) ............................................................................................19
8.2. Record Retention ............................................................................................................20
9. ADVERSE EVENT REPORTING......................................................................................20
9.1. Adverse Events (AEs) ....................................................................................................20

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9.2. Reporting Period .............................................................................................................21
9.3. Definition of an AE ........................................................................................................21
9.4. Abnormal Test Findings .................................................................................................22
9.5. Serious Adverse Events ..................................................................................................22
9.5.1. Potential Cases of Drug-Induced Liver Injury ..........................................................23
9.6. Hospitalization ................................................................................................................24
9.7. Severity Assessment .......................................................................................................25
9.8. Causality Assessment .....................................................................................................25
9.9. Exposure During Pregnancy ...........................................................................................26
9.10. Medication Error ..........................................................................................................27
9.11. Other Reportable Information ......................................................................................28
9.12. Reporting Requirements ...............................................................................................28
9.12.1. Serious Adverse Event Reporting Requirements ....................................................29
9.12.2. Non-Serious Adverse Event Reporting Requirements ............................................29
9.12.3. Sponsor Reporting Requirements to Regulatory Authorities..................................29
9.13. Communication of Issues .............................................................................................29
10. ETHICS..............................................................................................................................30
10.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ....................30
10.2. Ethical Conduct of the Study ........................................................................................30
10.3. Subject Information and Consent .................................................................................30
11. COMMUNICATION AND PUBLICATION OF STUDY RESULTS.............................31
11.1. Communication of results by Pfizer .............................................................................31
11.2. Publications by treating physicians ..............................................................................32
12. REFERENCES ..................................................................................................................33
FIGURES
Figure 1. Study Design ...........................................................................................................7
APPENDICES
Appendix 1. Sample Subject Global Assessment of  Disease Activity .................................35
Appendix 2. Sample Physician Global Assessment of Disease Activity ..............................36
Appendix 3. Sample Subject Morning Stiffness Worksheet .................................................37
Appendix 4. DAS28 Calculation ...........................................................................................38
Appendix 5. Funktionsfragebogen Hannover (FFbH) ...........................................................39
Appendix 6. EQ-5D ...............................................................................................................40
Appendix 7. Sample Patient Pain Visual Analog Scale ........................................................41
Appendix 8. Radiographs ......................................................................................................42

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Appendix 9. Abbreviations ....................................................................................................43

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1. INTRODUCTION
Rheumatoid arthritis (RA) affects almost 1% of the population and is associated with rapid 
functional loss and reduced life expectancy.  Disease remission and radiographic non-
progression are goals of treatment of RA.  For patients with RA, a variety of ‘conventional’
and novel biologic treatments (Disease Modifying Antirheumatic Drugs, DMARDs) are 
available. Numerous clinical trials and extensive post marketing surveillance have 
demonstrated the high efficacy and favorable safety profile of biologic drugs in comparison 
with traditional DMARDs.
Several randomized double blind clinical trials (COMETa, TEMPOb, c) have demonstrated the 
efficacy of Etanercept alone and in combination with methotrexate (MTX). Etanercept in 
combination with MTX reduced disease activity, slowed radiographic progression and 
improved function more effectively than either monotherapy.  Furthermore, a statistically 
significant improvement of the Total Sharp Score (TSS) has been reported for the 
combination suggesting that regression of erosion may occur in some patientsb, c, d
Psoriatic Arthritis (PsA) is a chronic inflammatory disorder characterised by arthritis and 
psoriasis, variably associated with other extra-articular manifestations. It has traditionally 
been considered a milder and less disabling disease than RA, however this view has recently 
been challenged by a number of studies showing approximately 40% of patients with PsA 
develop joint erosion and damage
.
e, f
Several studies have demonstrated the efficacy of Etanercept versus placebo in reducing the 
signs and symptoms of PsA and psoriasis
.
g, h.  In addition, inhibition of radiological 
progression was demonstrated using a modification of the Sharp Score to include joints 
frequently affected in PsAh, i
1.1. Background and Rationale 
.
Randomized clinical trials evaluate efficacy in selective groups of patients defined by strict 
inclusion criteria. However, the value of these trials in predicting effectiveness in a "real 
world" situation may have limitations. Data from the German biologics register (RABBIT) 
which includes patients that are out-with routine practice, estimate that around 21-33% of 
patients included in the register would have been eligible for the major trialsj.  Thus patients 
recruited to such tightly controlled studies reflect only a proportion of the patient population 
treated with biologic agents in routine care. 
It is known from the COMET trial that patients who start Etenercept in combination with 
MTX treatment early have a great chance of reaching clinical remission and radiographic 
non-progression than with MTXa. It is unclear however, how many patients with early 
arthritis achieve remission and radiographic non-progression under the conditions of routine 
rheumatologic care using local recommendations of Etanercept treatment (inadequate 
response to at least 2 DMARDs, one of which being MTX). 

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In addition, evidence suggests that radiographic progression may continue in patients 
receiving conventional treatment, even when clinical remission is achieved; the so-called 
‘Silent Progressor’k, l, m
This study aims to collect data on radiological progression and disease activity during routine 
use of Etanercept in RA and PsA in Germany.
.
Please refer to the Product Label (SMPC) for further information on Etanercept.  
2. STUDY OBJECTIVES AND ENDPOINTS
This is a non-interventional (NI), prospective, multi-center study to evaluate the radiological 
efficacy in patient with RA or PsA in routine treatment monitoring within a time interval of 
12 to 18 months. Additionally, data of the disease activity in the same time window will be 
documented quarterly. 
The radiological progression under Etanercept treatment will be compared to the radiological 
progression before Etanercept therapy in the same patient.  Therefore, radiographs that were 
made in the patient’s history 12-48 months before treatment with Etanercept will be 
collected. 
Patients with one existing radiograph of hands and feet (< 6 weeks prior to Etanercept 
treatment) and optional one or more existing radiographs taken in patient’s history 12 – 48 
months before treatment with Etanercept will be recruited. According to the German 
recommendations for patients treated with biologics, the biologic therapy will be monitored 
by annually recorded radiographs. If available, these images will be collected in this NI trial.
2.1. Endpoints
2.1.1. Primary Endpoint:
a.
Change in Radiographic Progression, measured by the “van der Heijde Sharp Score” for 
patients with RAn.
b. Change in Radiographic Progression measured by  the “PsA scoring method based on the 
Sharp Scoring Method of RA” for patients with PsAo. 
2.1.2. Secondary Endpoints:
c.
Relationship between radiographic progression and disease duration. 
d. Comparison between radiographic progression before and under treatment with 
Etanercept. 
e.
Change of Hannover Functional Ability Questionnaire (
Appendix 5
Funktionsfragebogen Hannover) 
(FFbH) (
).
f.
Change of Disease Activity Score (DAS) (RA patients only) (Appendix 4).

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g. Assessment of involved body surface area (BSA) (PsA patients only)  
a. Estimation of BSA affected by psoriasis may be done by using hand palm area, which 
represents approximately 1% of total body surface. 
3. STUDY DESIGN
This is an NI, prospective, multi-center study to evaluate the safety and radiological efficacy 
in patient with RA or PsA in routine treatment monitoring within a time interval of 12 to 18 
months.  Additionally, data on disease activity in the same time window will be documented 
quarterly. 
Patients with one existing radiograph of hands and feet (< 6 weeks prior or after Etanercept 
treatment) and one planned consecutive radiograph of hand and feet taken over 12 to 18 
months will be recruited, according to German recommendations for patients treated with 
biologics. 
Additionally, one historic radiograph should be collected if available, during a period of 12 to 
48 months prior to start of treatment with Etanercept.  This is optional.  
The recruitment period will be 18 months’ duration.  The overall study will be 36 months’ 
duration. 
Figure 1. Study Design
4. STUDY POPULATION
All subjects enrolled should meet the usual prescribing criteria for Etanercept as per the local 
product information and should be entered into the study at the treating physician’s 
discretion.  
4.1. Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriately qualified member 
of the investigator’s study team before subjects are included in the study. 
Week 0
Start of 
Documentation
0- 6 weeks prior or 
after Etanercept 
treatment start
Enrolment
Baseline 
radiographs
Endpoint
Measurement
Month 
12-18

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Evidence of a personally signed and dated informed consent document indicating that the 
subject (or a legally acceptable representative) has been informed of all pertinent aspects of 
the study is a requirement for inclusion into this study. 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
x
Subjects who are willing and able to comply with scheduled visits, treatment plan, 
laboratory tests, and other study procedures. 
x
Definitive diagnosis of RA or PsA. 
x
Biologic naïve. 
x
Eligible for Etanercept treatment according to Summary of Product Characteristics 
(SmPC). 
x
Age t 18 years. 
x
One plain radiograph of hands and feet (Anteroposterior) within 6 weeks prior to 
initiation of treatment with Etanercept and one planned consecutive radiograph of hand 
and feet taken over 12 to 18 months according to German recommendations for patients 
treated with biologics.  
4.2. Exclusion Criteria
Subjects with any of the following conditions or characteristics will be excluded from study 
enrollment: 
1. Age <18 years at time of consent.
x
Receipt of any investigational drug within 3 months of study inclusion. 
x
Exclusion Criteria according to the Enbrel®
x
Hypersensitivity to the active substance (etanercept) or to any of the excipients.
SmPC, with particular attention to: 
x
Sepsis or risk of sepsis.
x
Active infections, including chronic or localised infections. 
x
6XEMHFWVZKRKDYHUHFHLYHGDQ\SUHYLRXVWUHDWPHQWZLWKHWDQHUFHSWRURWKHU71)Į
inhibitors or biologic agents 
x
Subjects who are investigational site staff members or subjects who are Pfizer employees 
directly involved in the conduct of the trial. 

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5. STUDY TREATMENT AND DURATION
The use and dosage recommendations for Etanercept will take place on the basis of the 
approved Product Label / SmPC and will be adjusted solely according to medical and 
therapeutic necessity.
Patients will be observed for a period up to 18 months following initiation of Etanercept.
Patients will complete the study either following planned radiological monitoring between 12 
and 18 months or after 18 months following initiation of Etanercept.
6. STUDY PROCEDURES 
The primary objective of this NI study is to evaluate the radiographic progression under 
practice conditions in a time interval of 12 to 18 months in patients with RA or PsA.
In Germany, radiographs are being routinely taken to document the course of the rheumatic 
disease and to guide on therapy decisions.  The quality of radiographs must be standardised 
among the participating rheumatologists. The standard x-ray positioning for hands and feet 
is as follows:
h. The hands are to be imaged separately on a single 18x24 film. 
i.
Optimized positioning of the hands (wrist and forearm flat on the table/cassette). 
j.
Hands centered horizontally on the half of the cassette to be exposed so that the 
metacarpo-phalangeal joints are midline and the position of the central ray vertically 
between the 2nd and 3rd
k. X-ray of the feet sedentary, both feet on a 18x24 film flat on the cassette. 
metacarpo-phalangeal joints. 
All radiographs will be checked for eligibility for reading by the rheumatologists and will 
then be sent to the external CRO. There, the radiographs will be digitalized if necessary, 
pseudonymized, and sent to readers who read the radiographs independently. 
Additionally to the radiographic progression in the present observational trial the course of 
the disease of patients with RA or PsA resp. shall be documented by the treating physician. 
Radiographs are collected at different time points:
Visit 1:  
One plain radiograph of hands and feet (Anteroposterior) within 6 weeks prior 
to initiation of treatment with Etanercept (mandatory, inclusion criteria). 
Visit 1: 
Optional one historical radiograph of hands and feet (Anteroposterior) taken 
12-48 months prior to initiation of treatment with Etanercept.  If more than 
one radiograph has been taken in this time period, the earliest one will be 
collected.

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Visit 5, 6 or 7: One plain radiograph of hands and feet (Anteroposterior) taken 12 – 18 
months after initiation of treatment with Etanercept (not mandatory, only if 
available). The participation on the trial will end with the visit when the 
radiograph will be taken or, if no radiograph will be made, with visit 7. 
During the course of the NI trial up to seven visits are planned: At the beginning of the 
survey (Visit 1), in the course of the treatment after 13 weeks (Visit 2), after 26 weeks (Visit 
3), after 39 weeks (Visit 4) after 52 weeks (Visit 5), after 65 weeks (Visit 6) and after 78
weeks (Visit 7).  If the second radiograph recommended by the German society of 
Rheumatology for the treatment with biologics will be taken in visit 5 (after 52 weeks) or 
visit 6 (after 65 weeks) the participation of the patient in this trial will end with this visit. 
Otherwise the participation will end with Visit 7. As this is an NI study the visit interval 
reflects the current practice and can be adjusted by the treating physician as needed. 
6.1. Effectiveness criteria
The efficacy of the treatment with Etanercept will be documented using, beside others, the 
following tools for the evaluation the course of the disease: 
l.
Disease activity (DAS 28) (Appendix 4) including the Patient’s Global Assessment 
(Appendix 1), number of swollen and tender joints and erythrocyte sedimentation rate. 
m. BSA for patients with PsA.
n. Duration of morning stiffness (Appendix 3).
o. Global assessment of disease activity by both physician and patient (Appendix 2,
Appendix 1).
p. C-reactive protein. 
q. Serum rheumatoid factor. 
r.
Nail involvement for patients with PsA. 
The physician receives a binder with clinical research forms for each patient where the data 
and findings of the patient are documented.  With the exception of the not mandatory 
documentation of the previous radiograph the collection of data is prospective, i.e. the 
documentation of previous courses of treatment is not provided. 
Dose and duration of treatment should be based on clinical and individual needs and are 
determined by the treating physician.  To provide accurate information of the treatment, the 
initial Etanercept dose and all changes and the reasons for changes are documented during 
the course of the evaluation.  The concomitant medication is determined by the treating 
physician and is registered in the documentation sheet.  

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6.2. Safety criteria
In contrast to the usual procedure for clinical trials in observational trials no selection of 
patients at baseline is made.  Thus, this study can provide new insights into the safety of 
Etanercept in the routine application. Therefore, all adverse events (AEs) that will occur 
during the observation period will be documented.  Additionally, at the end of the 
observation both, the physician and the patient will be asked the general tolerability of the 
treatment with Etanercept and reasons for premature discontinuation rates will be analyzed.  
6.3. Health Outcomes
As a main issue of this evaluation it shall be measured how many patients that will achieve
radiographic remission (non-progression) also achieve functional remission according to the 
Hannover Functional Ability Questionnaire (FFbH) (Appendix 5).  In addition, the health-
related quality of life will be measured using the EQ-5D questionnaire (Appendix 6). 
The analysis of the relationship between the duration of the disease and the radiographic 
progression before and under treatment with Etanercept is of special interest and will be 
analyzed.
A proportion of the German patients treated with Etanercept in routine practice participate on 
a special patient care program, called RUDI & PIT. In this program the patients will be 
educated on certain topics around the drug Etanercept like e.g. administration, storage or 
cooling of the drug to enhance the adherence to therapy.  It will be analyzed if participation 
on this program will influence health outcomes parameters like Quality of Life or treatment 
discontinuation rates.  
6.4. Optional (12 to 48 months prior to initation of Etanercept).  
6.5. The required Baseline Visit
s.
Informed Consent. 
t.
Medical History including primary disease (RA, PsA) duration since diagnosis. 
u. Demography. 
v. Inclusion/ Exclusion criteria according to protocol and SmPC. 
w. Prior drug treatment of primary diagnosis (RA or PsA). 
x. Concomitant drug treatment. 
y. Physical examination. 
z. Erythrocyte sedimentation rate (ESR). 
aa. C-reactive protein (CRP).

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bb. Serum rheumatoid factor (SRA). 
cc. Cyclic Citrullinated Protein (CCP).
dd. Documentation of co-morbidities.
ee. Number of swollen and tender joints. 
ff. Morning Stiffness (Appendix 3).
gg. Patient’s Global Assessment Appendix 1).
hh. Physician’s Global Assessment (Appendix 2).
ii. Pain Visual Analogue Scale (VAS) (Appendix 7).
jj. Assessment of involved BSA (PsA patients only). 
kk. Involvement of nails (PsA patients only). 
ll. Dactylitis (PsA patients only). 
mm.
Hannover Functional Ability Questionnaire 
Appendix 5
(FFbH) (
).
nn. EQ-5D Appendix 6).
oo. Participation at the RUDI & PIT Compliance Program.
pp. Required pre-treatment radiographs (within 6 weeks of treatment initiation) available or 
obtained. 
qq. Additional ‘historic’ radiographs collected 12 to 48 months prior to initiation of 
Etanercept treatment (optional).  Radiographs must meet the standards of the protocol 
attached in Appendix 8 and are quality checked by the treating physician.  
6.6. Study Period
6.6.1. Scheduled Visits 2-6  
[Visit 2/week 13; Visit 3/week 26; Visit 4/week 39; Visit 5/week 52; Visit 6/week 65] 
rr. Concomitant drug treatment including treatment of primary diagnosis (RA or PsA).
ss. ESR. 
tt. CRP. 
uu. AEs. 

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vv. Number of swollen and tender joints. 
ww.
Morning Stiffness (Appendix 3).
xx. Patient’s Global Assessment (Appendix 1).
yy. Physician’s Global Assessment (Appendix 2).
zz. VAS (Appendix 7).
aaa.
Assessment of involved BSA (PsA patients only). 
bbb.
Involvement of nails (PsA patients only). 
ccc.
Dactylitis (PsA patients only). 
ddd.
Hannover Functional Ability Questionnaire
Appendix 5
(FFbH)
).
eee.
EQ-5D (Appendix 6).
6.6.2. Final (or close out) Visit 7/week 78
fff. Concomitant drug treatment including treatment of primary diagnosis (RA or PsA).
ggg.
ESR. 
hhh.
CRP. 
iii. SRA.
jjj. CCP. 
kkk.
AEs. 
lll. Number of swollen and tender joints. 
mmm. Morning Stiffness (Appendix 3).
nnn.
Patients Global Assessment (Appendix 1).
ooo.
Physicians Global Assessment (Appendix 2).
ppp.
Pain VAS (Appendix 7).
qqq.
Assessment of involved BSA (PsA patients only). 
rrr. Involvement of nails (PsA patients only). 
sss.Dactylitis (PsA patients only) 

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ttt. Hannover Functional Ability Questionnaire
Appendix 5
(FFbH) (
).
uuu.
EQ-5D (Appendix 6).
vvv.
Plain Radiographs, hands and feet (Appendix 8). 
6.7. Follow-up Visit
A follow up assessment will take place only for those patients with an ongoing treatment-
related AE at the end of the study period.  The follow up will be scheduled approximately 28 
days following the end of study and can be done by phone. 
6.8. Subject Withdrawal
Subjects experiencing AEs as listed in the Etanercept SmPC (with particular attention paid to 
Sections 4 (Contraindications), 5 (Special Warnings and 6 (Precautions) should be monitored 
and if indicated, treatment should be withdrawn according to provision of the SmPC. 

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6.9. Schedule of Activities
Study Week
Baseline 
(Enrolment)
11
Week 13
Week 26
Week 39
Week 52
Week 65
Week 78
Visit Number
1
2
3
4
5
6
7
Informed Consent
x 
  
  
  
  
  
  
Anamnesis / Medical History
x
Demographic data
x
Inclusion/exclusion criteria
x
Treatment/Medication
  
  
  
  
  
  
  
Prior drug treatment
x 
  
  
  
  
  
  
Concomitant drug treatment
x
x
x
x
x
x
x
Safety
Physical examination
x 
  
  
  
  
  
  
Inflammatory markers
x 
x 
x 
x 
x 
x 
x 
Documentation of Comorbidities
x
Documentation of AE
x
x
x
x
x
x
Efficacy
Number of swollen and tender joints
x 
x 
x 
x 
x 
x 
x 
Morning stiffness
x 
x 
x 
x 
x 
x 
x 
Patients Global Assessment
x
x
x
x
x
x
x
Physicians Global Assessment
x
x
x
x
x
x
x
Pain VAS
x 
x 
x 
x 
x 
x 
x 
Additionally for PsA-patients
BSA of psoriatic skin
x
x
x
x
x
x
x
Nail involvement
x
x
x
x
x
x
x
Dactylitis
x 
x 
x 
x 
x 
x 
x 
Health Outcomes
Hannover Functional Ability Questionnaire (FFbH)
x
x
x
x
x
x
x
EQ-5D
x
x
x
x
x
x
x
Participation at the Etanercept compliance Program (Rudi  Pit)
x
Radiologie/Radiology
Mandatory radiograph

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Study Week
Baseline 
(Enrolment)
11
Week 13
Week 26
Week 39
Week 52
Week 65
Week 78
Visit Number
1
2
3
4
5
6
7
1st picture not older than 6 weeks before 1st treatment with 
Etanercept
x
Optional radiographs
  
  
  
  
  
  
  
Optional: Historic picture, recorded between 12 and 48 month before 
1st treatment with Etanercept
(x)
  
  
  
  
  
  
Documentation of Disease activity at the timepoint of the "historic" 
radiograph
  
  
  
  
  
  
  
Supportive therapy
(x)
  
  
  
  
  
  
DAS 28
(x)
Inflammatory markers
(x)
Recording of a 2nd radiograph according to the recommendations of the German Society of Rheumatology. 
Earliest timepoint of this picture: 52 weeks after 1st treatment with Etanercept. After the second radiograph the 
final visit will be done. If radiograph not available from Week 52 to Week 78, the observational phase will end 
in Week 78.
(x)
(x)
(x)

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7. DATA ANALYSIS/STATISTICAL METHODS
The data collected and statistical methods proposed for analysis in this study will be 
documented in an NI Statistical Analysis Plan, which will be maintained by the sponsor.
This plan will detail the interim analyses as well as the full analysis once the database is 
complete.  This document may modify the plans outlined in the protocol; however, any major 
modifications will be reflected in an NI protocol amendment. 
The intention-to-treat population will be used for all effectiveness analyses. It is defined as 
patients who received at least one dose of Etanercept. Missing values will be assumed to be 
missing at random and not imputed.
7.1. Sample Size Calculation
This is an NI study and as such a formal sample size calculation is not required.  However it 
is planned to enroll 1200 RA and approximately 300 PsA patients.  
The change from baseline in radiographic progression (TSS) in RA subjects from the 
COMET1
For PsA, the Ravindran
 study based on a combination of MTX and Etanercept was 0.27 (standard deviation 
of 3.4) indicating that 1200 subjects would have 78% power at the 5% significance level. 
 i
7.2. Effectiveness Analysis  
paper indicates a mean yearly radiographic progression (modified 
TSS [mTSS]) of 2.85 with a standard deviation of 5.22.  Sample size estimation based on this 
paper would indicate less than 100 subjects would be required to demonstrate this level of 
progression at >90% power and at the 5% significance level.  It is anticipated that as many as 
300 subjects with PsA may be included into the study. 
The mean changes from baseline in the van der Heijde Sharp Score (TSS) (RA subjects only) 
will be summarised.  The number and percentage of subjects with increase (>0.5), no change 
(-0.5 to 0.5) or decrease (<-0.5) in TSS will also be presented by visit.  Subjects with no 
change or a decrease can be said to be in Radiographic remission. 
The mean changes from baseline in the mTSS (PsA subjects only) will be summarised. The 
number and percentage of subjects with increase (>0.5), no change (-0.5 to 0.5) or decrease 
(<-0.5) in mTSS will also be presented by visit. 
The change in the VAS from baseline will be summarised by visit.
The relationship between radiographic progression (TSS or mTSS) and disease duration will 
be assessed via a regression model with progression as the dependent variable and disease 
duration as the independent variable.  Patients with RA and PsA will be analysed separately 
using data from the baseline visit (pre Etanercept radiograph).  Additional covariates/factors 

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will be considered and documented in the Statistical Analysis Plan.  These may include the 
following: 
www. Radiographic progression prior to start of Etanercept (historical radiograph) 
xxx.
Patient’s global assessment (Appendix 1).
yyy.
Pain (VAS) (Appendix 7).
zzz.
Hannover Functional Ability Questionnaire (
Appendix 5
FFbH) (
)/
aaaa.
Disease activity score (DAS 28) (RA patients) (Appendix 4).
bbbb. BSA (PsA patients). 
A paired t-test will be performed on the TSS from before and after Etanercept treatment. The 
RA and PsA patients will be analysed separately.  This will be performed on the TSS score 
from the pre Etanercept radiograph and the TSS from the 12-18 month radiograph (Visit 5, 6 
or 7).
Physician (and Patient) Global Assessment of arthritis will be summarized by visit. 
The FFbH will be sumarised by visit.  The number and percentage of subjects with functional 
remission will also be presented by visit.  
The DAS-28 score (RA subjects only) will be summarized by visit. 
BSA (PsA subjects only) will be summarized by visit.
The EQ-5D will be summarized by visit.
Duration of morning stiffness will be summarized by visit.
7.3. Safety Analysis 
Concomitant medications will be summarized. All AEs collected will be summarized. Any 
SAEs reported will be summarized.
7.4. Interim Analysis 
7.4.1. First Interim analysis
Data sets of est. 1000 patients (first visit, radiograph < 6 weeks before 1st visit and 
“historical” radiograph 12-48 months before first visit) will be eligible for statistical analysis 
at the beginning of 2013. 

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X-ray progression before treatment with Etanercept will be analyzed for potential 
confounding variables, e.g. disease duration, clinical outcome parameters and other disease 
characteristics like:
cccc.
Patient’s Global Assessment.
dddd. Pain (VAS). 
eeee.
FFbH. 
ffff.
Disease activity score (DAS 28) (RA patients). 
gggg. BSA (PsA patients). 
7.4.2. Second Interim Analysis
Complete data sets of est. 500 patients will be eligible for statistical analysis at the beginning 
of 2014. 
X-ray progression before treatment with Etanercept will be analyzed for potential 
confounding variables, e.g. disease duration, clinical outcome parameters and other disease 
characteristics like:
hhhh. Patient’s global assessment.
iiii.Pain (VAS).
jjjj.FFbH. 
kkkk. Disease activity score (DAS 28) (RA-patients). 
llll.BSA (PsA-patients). 
8. DATA COLLECTION AND DATA MANAGEMENT 
8.1. Case Report Forms (CRFs)
A CRF should be completed for each included subject.  The completed original CRFs are the 
sole property of Pfizer and should not be made available in any form to third parties, except 
for authorized representatives of Pfizer or appropriate regulatory authorities, without written 
permission from Pfizer.
The treating physician has ultimate responsibility for the collection and reporting of all 
clinical, safety and laboratory data entered on the CRFs and any other data collection forms 
(source documents) and ensuring that they are accurate, authentic / original, attributable, 

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complete, consistent, legible, timely (contemporaneous), enduring and available when 
required.  The CRFs must be signed by the treating physician or by an authorized staff 
member to attest that the data contained on the CRFs is true. Any corrections to entries made 
in the CRFs, source documents must be dated, initialed and explained (if necessary) and 
should not obscure the original entry.
In most cases, the source documents are the hospital's or the physician's subject chart. In
these cases data collected on the CRFs must match the data in those charts.  
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the treating physician’s site as well as at Pfizer and 
clearly identify those data that will be recorded in the CRF, and for which the CRF will stand 
as the source document. 
8.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the treating 
physician agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent forms, copies of all CRFs, SAE forms, source documents, and detailed 
records of treatment disposition, and adequate documentation of relevant correspondence (eg, 
letters, meeting minutes, telephone calls reports).  The records should be retained by the 
treating physician according to local regulations, or as specified in the Clinical Study 
Agreement, whichever is longer. 
If the treating physician becomes unable for any reason to continue to retain study records for 
the required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another treating 
physician, another institution, or to an independent third party arranged by Pfizer. The 
treating physician must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met. 
9. ADVERSE EVENT REPORTING
9.1. Adverse Events (AEs)
All observed or volunteered AEs regardless of treatment group (if applicable) or suspected 
causal relationship to Etanercept will be recorded on the AE page(s) of the CRF as follows.  
For all AEs, the treating physician must pursue and obtain information adequate both to 
determine the outcome of the AEt and to assess whether it meets the criteria for classification 
as a serious adverse event (SAE) (see section "Serious Adverse Events”) requiring immediate 
notification to Pfizer or a Pfizer-designated representative. For all AEs, sufficient 
information should be obtained by the treating physician to determine the causality of the 

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AE. The treating physician is required to assess causality. For AEs with a causal 
relationship to Etanercept, follow-up by the treating physician is required until the event or 
its sequelae resolve or stabilize at a level acceptable to the treating physician, and Pfizer 
concurs with that assessment.
9.2. Reporting Period
For SAEs, the reporting period to Pfizer or its designated representative begins from the time 
that the subject provides informed consent or signed data privacy statement, which is 
obtained prior to the subject’s participation in the study , i.e., prior to undergoing any study-
related procedure and/or receiving investigational product, through and including 28 calendar 
days after the last administration of the study drug within the observational period.  Any SAE
occurring any time after the reporting period must be promptly reported if a causal 
relationship to investigational product is suspected. 
9.3. Definition of an AE 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage. Examples of AEs include but are not limited to:  
mmmm.
Abnormal test findings; 
nnnn. Clinically significant symptoms and signs;
oooo. Changes in physical examination findings; 
pppp. Hypersensitivity;
qqqq. Progression/worsening of underlying disease. 
Additionally, they may include the signs or symptoms resulting from: 
rrrr.
Drug overdose; 
ssss.
Drug withdrawal; 
tttt.Drug abuse;
uuuu. Drug misuse; 
vvvv. Drug interactions;
wwww.
Drug dependency; 

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xxxx. Extravasation;
yyyy. Exposure During Pregnancy; 
zzzz.
Exposure during breast feeding; 
aaaaa. Medication Error. 
9.4. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 
bbbbb. Test result is associated with accompanying symptoms, and/or
ccccc. Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
ddddd. Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy, and/or 
eeeee. Test result is considered to be an AE by the treating physician or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
9.5. Serious Adverse Events
An SAE is any untoward medical occurrence at any dose that:
fffff.
Results in death; 
ggggg. Is life-threatening (immediate risk of death);
hhhhh. Requires inpatient hospitalization or prolongation of existing hospitalization; 
iiiii.
Results in persistent or significant disability/incapacity;
jjjjj.
Results in congenital anomaly/birth defect.
Lack of efficacy should be reported as an AE when it is associated with an SAE.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 

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result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
9.5.1. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate transaminase (AST) and/or alanine transaminase (ALT) 
concurrent with abnormal elevations in total bilirubin that meet the criteria outlined below in 
the absence of other causes of liver injury are considered potential cases of drug-induced 
liver injury (potential Hy’s Law cases) and should always be considered important medical 
events.   
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions.  Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values: 
kkkkk. Subjects with AST or ALT baseline values within the normal range who subsequently 
present with AST or ALT WLPHV the upper limit of normal concurrent with a total 
bilirubin WLPHVWKHXSSHUOLPLWRIQRUPDOZLWKQRHYLGHQFHRIKHPRO\VLVDQGDQ
alkaline phosphatase  WLPHVWKHXSSHUOLPLWRIQRUPDORUQRWDYDLODEOH
lllll.
Subjects with pre-existing AST or ALT baseline values above the normal range who 
subsequently present with AST or ALT WLPHVWKHEDVHOLQHYDOXHVDQGWLPHVWKH
upper limit of normal, or WLPHVWKHXSSHUOLPLWRIQRUPDOZKLFKHYHULVVPDOOHU
concurrent with a total bilirubin of WLPHVWKHXSSHU limit of normal and increased by 
one upper limit of normal over baseline or >3 times the upper limit of normal (whichever 
is smaller) with no evidence of hemolysis and an alkaline phosphatase  WLPHVWKH
upper limit of normal or not available. 
The subject should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history and physical assessment and for oncology studies, 
the possibility of hepatic neoplasia (primary or secondary) should be considered).  In addition 
to repeating AST and ALT, laboratory tests should include albumin, creatine kinase, total 
bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase (GGT), international 
normalized ratio (INR) and alkaline phosphatase.  A detailed history, including relevant 
information, such as review of ethanol, recreational drug and supplement consumption, 
family history, sexual history, travel history, history of contact with a jaundiced subject, 
surgery, blood transfusion, history of liver or allergic disease, and work exposure, should be 

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collected.  Further testing for acute hepatitis A, B, or C infection and liver imaging (e.g. 
biliary tract) may be warranted.  All cases confirmed on repeat testing as meeting criteria A 
or B, with no other cause for LFT abnormalities identified at the time should be considered 
potential Hy’s Law cases irrespective of availability of all the results of the investigations 
performed to determine etiology of the abnormal LFTs.  Such potential Hy’s Law cases
should be reported as SAEs.
9.6. Hospitalization 
AEs reported from studies associated with hospitalization or prolongation of hospitalization 
are considered serious. Any initial admission (even if less than 24 hours) to a healthcare 
facility meets these criteria.  Admission also includes transfer within the hospital to an 
acute/intensive care unit (eg, from the psychiatric wing to a medical floor, medical floor to a 
coronary care unit, neurological floor to a tuberculosis unit). 
Hospitalization does not include the following: 
mmmmm.
Rehabilitation facilities;
nnnnn. Hospice facilities;
ooooo. Respite care (eg, caregiver relief);
ppppp. Skilled nursing facilities;
qqqqq. Nursing homes; 
rrrrr.
Routine emergency room admissions; 
sssss. Same day surgeries (as outpatient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include:  
ttttt.
Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for work-
up of persistent pre-treatment lab abnormality);
uuuuu. Social admission (eg, subject has no place to sleep);
vvvvv. Administrative admission (eg, for yearly physical exam);
wwwww.
Protocol-specified admission during a study (eg, for a procedure required by 
the study protocol); 

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xxxxx. Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);
yyyyy. Pre-planned treatments or surgical procedures should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject. 
9.7. Severity Assessment
If required on the AE CRFs, the investigator will use the adjectives MILD, MODERATE, or 
SEVERE to describe the maximum intensity of the AE.  For purposes of consistency, these 
intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function. 
MODERATE
Interferes to some extent with subject's usual function. 
SEVERE
Interferes significantly with subject's usual function. 
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily a serious event.  For example, a headache may be severe (interferes significantly 
with subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above. 
9.8. Causality Assessment
The treating physician’s assessment of causality must be provided for all AEs (serious and 
non-serious). The treating physician must record the causal relationship in the CRF, as 
appropriate, and report such an assessment in accordance with the serious adverse reporting 
requirements if applicable.  
An treating physician's causality assessment is the determination of whether there exists a
reasonable possibility that Etanercept caused or contributed to an AE. If the treating 
physician's final determination of causality is unknown and the treating physician does not 
know whether Etanercept caused the event, then the event will be handled as related to 
Etanercept for reporting purposes.  If the treating physician’s causality assessment is 
“unknown but not related to investigational product”, this should be clearly documented in 
the CRF.  
In addition, if the investigator determines an SAE is associated with study procedures, the 
investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.

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9.9. Exposure During Pregnancy
For investigational products and for marketed products, an exposure during pregnancy (also 
referred to as exposure in-utero [EIU]occurs if: 
a.
A female becomes, or is found to be, pregnant either while receiving or having been 
directly exposed to (eg, environmental exposure) the investigational product, or the 
female becomes, or is found to be, pregnant after discontinuing and/or being directly 
exposed to the investigational product (maternal exposure); 
b. A male has been exposed, either due to treatment or environmental, to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy (paternal exposure). 
If any study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to Pfizer on an EIU Form.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a nurse 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) using the EIU Form.  This must be done irrespective of whether an AEhas occurred 
and within 24 hours of awareness of the pregnancy.  The information submitted should 
include the anticipated date of delivery (see below for information related to induced 
termination of pregnancy). 
Follow-up is conducted to obtain pregnancy outcome information on all Exposure during 
pregnancy reports with an unknown outcome.  The investigator will follow the pregnancy 
until completion or until pregnancy termination (ie, induced abortion) and then notify Pfizer 
of the outcome.  The investigator will provide this information as a follow up to the initial 
EIU Form.  The reason(s) for an induced abortion should be specified.  An EIU report is not 
created when an ectopic pregnancy report is received since this pregnancy is not usually 
viable.  Rather, an SAE case is created with the event of ectopic pregnancy.
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (ie, 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in an 
aborted fetus, stillbirth or neonatal death]), the investigator should follow the procedures for 
reporting SAEs.
In the case of a live birth, the “normality” of the newborn can be assessed at the time of birth 
(ie, no minimum follow-up period of a presumably normal infant is required before an EIU
Form can be completed).  The “normality” of an aborted fetus can be assessed by gross 
visual inspection, unless pre-abortion test findings are suggestive of a congenital anomaly. 
Additional information about pregnancy outcomes that are classified as SAEs follows: 

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zzzzz. “Spontaneous abortion” includes miscarriage and missed abortion;
aaaaaa.All neonatal deaths that occur within 1 month of birth should be reported, without 
regard to causality, as SAEs.  In addition, any infant death after 1 month that the 
investigator assesses as possibly related to the exposure during pregnancy to the 
investigational medication should be reported. 
Additional information regarding the exposure during pregnancy may be requested by the 
investigator.  Further follow-up of birth outcomes will be handled on a case-by-case basis 
(eg,. follow-up on preterm infants to identify developmental delays).  In the case of paternal 
exposure, the investigator will provide the study subject with the EIU Pregnant Partner 
Release of Information Form to deliver to his partner.  The Investigator must document on 
the EIU Form that the subject was given this letter to provide to his partner.
9.10. Medication Error
A medication error is any preventable event that may cause or lead to inappropriate 
medication use or patient harm while the medication is in the control of the health care 
professional, patient, or consumer.  Such events may be related to professional practice, 
health care products, procedures, and systems including: prescribing; order communication; 
product labeling, packaging, and nomenclature; compounding; dispensing; distribution; 
administration; education; monitoring; and use.   
Medication errors include:
bbbbbb.
Near misses, involving or not involving a patient directly (eg, 
inadvertent/erroneous administration, which is the accidental use of a product outside of 
labeling or prescription on the part of the healthcare provider or the patient/consumer); 
cccccc.Confusion with regard to invented name (eg, trade name, brand name). 
The treating physician must submit the following medication errors to Pfizer within 24 hours 
of awareness, irrespective of whether an AEoccurred:
dddddd.
Medication errors involving patient exposure to the product, whether or not 
the medication error is accompanied by an AE.
eeeeee.Medication errors including potential medication errors or near misses that do not 
involve a patient directly.  When a medication error does not involve patient exposure to 
the product the following minimum criteria constitute a medication error report:
b. An identifiable reporter;
c.
A suspect product; 

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d. A medication error including potential medication error or near miss.
9.11. Other Reportable Information
Certain information, although not considered an SAE, must be recorded, reported, and followed 
up as indicated for an SAE.  This includes:
ffffff. Pregnancy exposure to a test article, except for exposure to prenatal vitamins.  If a 
pregnancy is confirmed, use of the test article must be discontinued immediately.  
Information about pregnancy exposure includes the entire course of pregnancy and 
delivery, and perinatal and neonatal outcomes, even if there are no abnormal findings.  
Both maternal and paternal exposure are considered other reportable information.  For 
exposure involving the female partner of a male subject, the necessary information must 
be collected from the subject, while respecting the confidentiality of the partner. 
gggggg.
Lactation exposure to a test article with or without an AE.
hhhhhh.
Overdose of a test article as specified in this protocol with or without an AE.
Baby formula overdoses without any AEs are excluded. 
iiiiii.
Inadvertent or accidental exposure to a test article with or without an AE.
jjjjjj.
Amyotrophic lateral sclerosis
kkkkkk.
Demyelination and multiple scleriosis
llllll.
Guillain-Barrè Syndrome 
mmmmmm.
Lymphoma 
nnnnnn.
Mycosis fungoides;  
oooooo.
Cutaneous T-cell lymphoma;
pppppp.
Progressive Multifocal Leukoencephalopathy (PML) 
9.12. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.   
If an SAE occurs, expedited reporting will follow local and international regulations, as 
appropriate. 

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9.12.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of awareness of the event by the 
treating physician.  In particular, if the SAE is fatal or life-threatening, notification to Pfizer 
must be made immediately, irrespective of the extent of available AE information.  This 
timeframe also applies to additional new information (follow-up) on previously forwarded 
serious AE reports as well as to the initial and follow-up reporting of exposure during 
pregnancy, exposure during breast feeding and medication error cases.   
In the rare event that the treating physician does not become aware of the occurrence of an 
SAE immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
treating physician is to report the event within 24 hours after learning of it and document the 
time of his/her first awareness of the AE. 
For all SAEs, the treating physician is obligated to pursue and provide information to Pfizer 
in accordance with the timeframes for reporting specified above.  In addition, a treating 
physician may be requested by Pfizer to obtain specific additional follow-up information in 
an expedited fashion.  This information collected for SAEs is more detailed than that 
captured on the AE CRF.  In general, this will include a description of the AE in sufficient 
detail to allow for a complete medical assessment of the case and independent determination 
of possible causality.  Information on other possible causes of the event, such as concomitant 
medications and illnesses must be provided.  In the case of a subject death, a summary of 
available autopsy findings must be submitted as soon as possible to Pfizer or its designated 
representative. 
9.12.2. Non-Serious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information. 
9.12.3. Sponsor Reporting Requirements to Regulatory Authorities
AE reporting, including suspected serious unexpected adverse reactions, will be carried out 
in accordance with applicable local regulations.
9.13. Communication of Issues 
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable 
Competent Authority in any area of the world, or if the treating physician is aware of any 
new information which might influence the evaluation of the benefits and risks of Etanercept,
Pfizer should be informed immediately.   

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In addition, the treating physician will inform Pfizer immediately of any urgent safety 
measures taken by the treating physician to protect the study subjects against any immediate 
hazard, and of any serious breaches of this NI study protocol that the treating physician
becomes aware of.
10. ETHICS
10.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
The IRB/IEC will review and approve the protocol before any subjects are enrolled.  
10.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, such as 
the German Drug Law (AMG) and with the German BfArM-guideline for observation 
studies (Anwendungsbeobachtungen [AWB]) and local consensus recommendations, as well 
as with scientific purpose, value and rigor and follow generally accepted research practices 
such as Good Pharmacoepidemiology Practices (GPP) issued by the International Society for 
Pharmacoepidemiology (ISPE), the International Society for Pharmacoeconomics and 
Outcomes Research (ISPOR) guidances, Pharmaceutical Research and Manufacturers of 
America (PhRMA) guidelines and similar.  The drug used is a marketed product and has to 
be prescribed according to German Drug Law AMG §67, 6.  The patient will give written 
informed consent to the study.  The IRB/IEC will review and approve the protocol before any 
subjects are enrolled.
10.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws.  In case of data transfer, Pfizer will maintain high standards of 
confidentiality and protection of subject personal data. 
The informed consent form must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements as applicable.
The informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC and Pfizer before use. 
The treating physician must ensure that each study subject, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation. The treating physician, or a person designated by the 
treating physician, will obtain written informed consent from each subject or the subject's 
legally acceptable representative before any study-specific activity is performed. The 
treating physician will retain the original of each subject's signed consent form. 

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11. COMMUNICATION AND PUBLICATION OF STUDY RESULTS
11.1. Communication of results by Pfizer
Pfizer fulfils its commitment to publicly disclose the results of studies through posting the 
results of this study on ClinicalStudyResults.org. Pfizer posts the results of studies that fall 
into either of the following categories: 
qqqqqq.
Studies that Pfizer registered on www.clincaltrials.gov
rrrrrr. All other studies for which the results have scientific or medical importance as 
determined by Pfizer.
regardless of the 
reason for registration; OR
Results are posted in two formats:  
ssssss. The results of studies applicable under the US Food and Drug Administration 
Amendments Act of 2007 (FDAAA) and/or An Act Regarding Advertising by Drug 
Manufacturers and Disclosure of Clinical Trials (state of Maine Reporting Requirements) 
are posted on ClinicalTrials.gov
tttttt.
The results of all required studies (even if not previously registered to 
ClinicalTrials.gov) and any voluntarily registered studies are posted 
on
in a tabular format called Basic Results.  
ClinicalStudyResults.org
For studies involving a Pfizer product, the timing of the posting depends on whether the 
Pfizer product is approved for marketing in any country at the time the study is completed: 
in a format called a PhRMA website synopsis (PWS), the 
format established by the ICH-E3 Clinical Study Report (CSR) Synopsis. 
uuuuuu.
For studies involving products already approved in any country and applicable 
under FDAAA and/or state of Maine, Pfizer posts results within one year of the primary 
outcome completion date (PCD).  For all other studies that do not involve a Pfizer 
product, Pfizer posts results one year from last, subject last visit (LSLV); 
vvvvvv.
For studies involving products that are not yet approved in any country, Pfizer 
posts the results of already-completed studies within 30 days after US regulatory 
approval or one year after the first ex-US regulatory approval of the product (if only 
submitted for approval ex-US);
wwwwww.
For studies involving products whose drug development is discontinued 
before approval, Pfizer posts the results within one year after such discontinuation. 

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PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical trial 
concluded according to the pre-specified protocol or was terminated.
Pfizer posts citations only for publications that are accessible in recognized (searchable) 
publication databases.  Single-centre results publications for a multi-centre study are 
generally not posted because they may not accurately reflect the results of the study. 
11.2. Publications by treating physicians  
Pfizer has no objection to publication by treating physician of any information collected or 
generated by treating physician, whether or not the results are favorable to the study drug.
However, to ensure against inadvertent disclosure of Confidential Information or unprotected 
Inventions, treating physician will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure before it is submitted or otherwise disclosed. 
Treating physician will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to Pfizer 
at least 30 days before they are submitted for publication or otherwise disclosed.  If any 
patent action is required to protect intellectual property rights, treating physician agrees to 
delay the disclosure for a period not to exceed an additional 60 days. 
Treating physician will, on request, remove any previously undisclosed Confidential 
Information (other than the Study results themselves) before disclosure.
As the Study is a multi-centre study, treating physician agrees that the first publication is to 
be a joint publication covering all centers.  However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the Study at all 
participating sites, treating physician is free to publish separately, subject to the other 
requirements of this Section. 
For all publications relating to the Study, Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship
Publication of study results is also provided for in the Clinical Study Agreement between 
Pfizer and the institution. In this section entitled Publications by Treating physicians, the 
defined terms shall have the meanings given to them in the Clinical Study Agreement.
,
established by the International Committee of Medical Journal Editors.

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12. REFERENCES
a.
Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D et al, Comparison 
of methotrexate with a combination of methotrexate and etanercept in active, early, 
moderate to severe rheumatoid arthritis (COMET): a randomized, double-blind, 
parallel treatment trial. Lancet 2008; 272: 375-382. 
b. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M et al. 
Therapeutic effect of a combination of Etanercept and methotrexate compared with 
each treatment alone in partients with rheumatoid arthritis: Double-blind randomised 
controlled trial. Lancet 2004; 363: 675-681. 
c.
van der Heijde D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H et al. 
Comparison of Etanercept and methotrexate, alone and in combination, in the 
treatment of Rheumatoid Arthritis: Two-year clinical and radiolographic results from 
the TEMPO study, a double blind randomised trial. Arthritis Rheum. 2006; 54: 1063-
1074
d. van der Heijde D, Landewe R, Klareskog L, Rodriguez-Valverde V, Settas L, 
Pedersen R, Fatenejad S. Presentation and analysis of data on radiographic outcome 
in clinical trials: Experience from the TEMPO study. Arthritis Rheum. 2005; 52: 49-
60
e.
Gladman DD, Shuckett R, Russell ML, Thorne JC, Schachter RK. Psoriatic Arthritis 
in Italian psoriatic patients. Q.J.Med.,1987; 62:127-141 
f.
Gladman DD, Stafford-Brady F, Chang CH, Lewandowski K, Russell ML. 
longitudinal study of clinical and radiological progression in psoriatic arthritis. J. 
Rheumalol. 1990; 17: 809-812 
g. Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B, Burge DJ. Etanercept in the 
treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000; 356: 
385-390. 
h. Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB et al. Etanercept treatment of 
psoriatic arthritis. Arthritis Rheum. 2004; 50: 2264-2272 
i.
Ravindran J, Cavill C, Balakrishnan C, Jones SM, Korendowych E, McHugh NJ. A 
modified Sharp score demonstrates disease progression in established psoriatic 
arthritis. Arthritis Car & Res 2010; 62: 86-91 
j.
Zink A, Strangefeld A, Schneider M, Herzer P, Hierse F, Stoyanova-Scholz M et al. 
Effectiveness of Tumor necrosis factor inhibitors in rheumatoid arthritis in an 
observational cohort study. Arthritis Rheum 2006; 54: 3399-3407 

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k. Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R et al. Effect of a 
treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a 
single-blind randomised controlled trial. Lancet 2004; 364:263-269 
l.
Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D et al. 
Clinical and radiographic outcomes of four different treatment strategies in patients 
with early rheumatoid arthritis (the BeSt study): a randomised, controlled study. 
Arthritis Rheum 2005; 52: 3381-3390 
m. Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K et al. An explanation for the 
apparent dissociation between clinical remission and continued deterioration in 
rheumatoid arthritis. Arthritis Rheum, 2008; 58:2958-2967 
n. van der Heijde D. How to read radiographs according to the Sharp/van der Heijde 
method. J Rheumatol 2000; 27: 261–63. 
o. van der Heijde D. Psoriatic arthritis imaging: A review of scoring methods. Ann 
Rheum Dis 2005; 64: (Suppl II) :ii61-ii64

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Appendix 1. Sample Subject Global Assessment of  Disease Activity

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Appendix 2. Sample Physician Global Assessment of Disease Activity 

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Appendix 3. Sample Subject Morning Stiffness Worksheet
The duration of morning stiffness should be determined by asking the following questions: 
Over the last 2 days, when did you wake in the morning?  __________ 
Over the last 2 days, when were you able to resume your normal activities without  
stiffness?  _________ 
  Check this box if you were not able to resume your normal activities without stiffness (ie. 
your stiffness never went away – 24 hours of stiffness). 

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Appendix 4. DAS28 Calculation 
In order to calculate the DAS28 the number of swollen joints and tender joints should be 
assessed using the 28 JOINT COUNT (tender28 and swollen28).  The ESR should be 
measured (in mm/hour).  In addition, the subject's general health measured on a VAS of 100 
mm must be obtained.  Using these data, the DAS28 can be calculated using the following 
formula:
DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * VAS 
GH (general health)
Joints assessed for the 28 joint count: 
PIP 1 (right and left) 
PIP 2 (right and left) 
PIP 3 (right and left) 
PIP 4 (right and left) 
PIP 5 (right and left) 
MCP 1 (right and left) 
MCP 2 (right and left) 
MCP 3 (right and left) 
MCP 4 (right and left)
MCP 5 (right and left) 
Wrists (right and left)
Elbows (right and left) 
Shoulders (right and left) 
Knees (right and left) 
PIP = Proximal interphalangeal joint
MCP = Metacarpophalangeal joint

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Appendix 5. Funktionsfragebogen Hannover (FFbH)

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Appendix 6. EQ-5D 

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Appendix 7. Sample Patient Pain Visual Analog Scale 

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Appendix 8. Radiographs 
In Germany, radiographs are being routinely taken to document the course of the rheumatic 
disease and to guide on therapy decisions.  The quality of radiographs must be standardised 
among the participating rheumatologists. The standard x-ray positioning for hands and feet 
is as follows:
xxxxxx.
The hands are to be imaged separately on a single 18x24 film 
yyyyyy.
Optimized positioning of the hands (wrist and forearm flat on the 
table/cassette)
zzzzzz.Hands centred horizontally on the half of the cassette to be exposed so that the 
metacarpo-phalangeal joints are midline and the position of the central ray vertically 
between the 2nd and 3rd
aaaaaaa.
X-ray of the feet sedentary, both feet on a 18x24 film flat on the cassette
metacarpo-phalangeal joints 

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Appendix 9. Abbreviations 
Abbreviation
Term
AE
Adverse Event
ALT
Alanine transaminase
AMG
German Drug Law
AST
Aspartate transaminase
BSA
Body surface area
CCP
Cyclic citrullinated protein
CRF
Case Report Form
CRP
C-reactive Protein
CSR
Clinical Study Report
DAS
Disease Activity Score
DMARD
Disease Modifying Antirheumatic Drugs
EIU
Exposure in Utero
ESR
Erythrocyte sedimentation rate
FDAAA
Food and Drug Administration Amendments Act
FFbH
Funktionsfragebogen Hannover
GCP
Good Clinical Practice
GGT
Gamma-glutamyl transferase
GPP
Good Pharmacoepidemiology Practices
IEC
Independent Ethics Committee
INR
International normalized ratio
IRB
Institutional Review Board
ISPE
International Society for Pharmacoepidemiology
ISPOR
International Society for Pharmacoeconomics and Outcomes Research
LSLV
Last subject, last visit
MCP
Metacarpophalangeal joint
mTSS
Modified Total Sharp Score
MTX
Methotrexate
NI
Non-Interventional
PCD
Primary Completion Date
PhRMA
Pharmaceutical Research and Manufacturers of America
PIP
Proximal interphalangeal joint
PML
Progressive multifocal leukoencephalopathy
PsA
Psoriatic Arthritis
RA
Rheumatoid arthritis
SAE
Serious Adverse Events
SmPC
Summary of Product Characteristics
SRA
Serum rheumatoid factor
TSS
Total Sharp Score
VAS
Visual Analogue Scale

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