Correlation of Anti-CCP With Disease Activity and Its Impact on Biological Response in PsA in Iraqi Patients
Conditions: Psoriatic Arthritis
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
Correlation of Anti-CCP with Disease 
Activity and its Impact on Biological 
Response in PsA in Iraqi Patients
Protocol number
B1801418
Protocol version identifier
Version 4.0
Date
27 July 2021
Active substance
Etanercept
Medicinal product
Etanercept
Research question and objectives
Determine the clinical impact of ACCP 
positivity for management (etanercept) in 
patients with PsA compared to negative 
ACCP patients.
Author
MD, M.Sc.
Pfizer Inc – Iraq
This document contains confidential information belonging to Pfizer.  Except as otherwise agreed to in 
writing, by accepting or reviewing this document, you agree to hold this information in confidence and not 
copy or disclose it to others (except where required by applicable law) or use it for unauthorized purposes.  In 
the event of any actual or suspected breach of this obligation, Pfizer must be promptly notified.
PPD
PPD

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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................2
2. LIST OF ABBREVIATIONS................................................................................................3
3. RESPONSIBLE PARTIES....................................................................................................5
4. AMENDMENTS AND UPDATES.......................................................................................6
5. MILESTONES.......................................................................................................................7
6. RATIONALE AND BACKGROUND..................................................................................8
7. RESEARCH QUESTION AND OBJECTIVES ...................................................................8
8. RESEARCH METHODS ......................................................................................................8
8.1. Study Design .............................................................................................................8
8.2. Setting........................................................................................................................9
8.2.1. Inclusion Criteria ..........................................................................................9
8.2.2. Exclusion Criteria.........................................................................................9
8.3. Data Sources..............................................................................................................9
8.4. Study Size................................................................................................................10
8.5. Data Management ...................................................................................................10
8.6. Data Analysis ..........................................................................................................10
8.7. Quality Control........................................................................................................10
8.8. Limitations of the Research Methods......................................................................10
8.9. Other Aspects ..........................................................................................................10
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................10
9.1. Patient Information..................................................................................................10
9.2. Patient Consent........................................................................................................11
9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..............11
9.4. Ethical Conduct of the Study ..................................................................................11
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................11
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........11
12. REFERENCES ..................................................................................................................12
13. LIST OF TABLES.............................................................................................................13
14. LIST OF FIGURES ...........................................................................................................13
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.........................................................13

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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
ACCP
Anti-Cyclic Citrullinated Peptide
ACR
American College of Rheumatology 
AE
Adverse Event
anti-CCP
Anti-Citrullinated Protein Antibody 
DAPSA
Disease Activity in Psoriatic Arthritis
DMARDs
Disease-Modifying Antirheumatic Drugs 
EULAR
European League Against Rheumatism 
GEP
Good Epidemiological Practice 
GPP
Guidelines for Good Pharmacoepidemiology 
Practices
IEA
International Epidemiological Association 
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ISPE
International Society for Pharmacoepidemiology 
ISPOR
International Society for Pharmacoeconomics and 
Outcomes Research
MTX
Methotrexate
NA
Not Applicable 
PsA
Psoriatic Arthritis
RA
Rheumatoid Arthritis
SAP
Statistical Analysis Plan (if applicable)

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Abbreviation
Definition
SPSS
Statistical Package for the Social Science (Software)
TNF
Tumor Necrosis Factor

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3. RESPONSIBLE PARTIES
Principal Investigator(s) of the Protocol
Name, degree(s)
Job Title
Affiliation
Address
MD, 
M.Sc.
Medical Advisor
NI Study Lead
Pfizer Inc – Iraq
PPD
PPD

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4. AMENDMENTS AND UPDATES
Amendment 
number
Date
Protocol 
section(s) 
changed
Summary of amendment(s)
Reason
1
22 June 
2021
Section 5
Updated to align with Study Report
Administrative
2
15 July 
2021
8.6
Clarified tools used for data analysis
Administrative
3
26 July 
2021
Throughout 
document
Spelling errors
Administrative
4
27 July 
2021
Throughout 
document
Spelling errors
Administrative

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5. MILESTONES
Milestone
Planned date
Actual Date
Start of data collection
01 July 2020
01 July 2020
End of data collection
01 August 2020
01 August 2020
Final study report
30 June 2021
29 June 2021

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6. RATIONALE AND BACKGROUND
Psoriatic arthritis is a chronic, systemic inflammatory arthritis that occurs in 6 to 42% of 
patients with psoriasis, affecting the peripheral joints, tendons, ligaments, and the axial 
skeleton. Current treatment guidelines for psoriatic arthritis recommends conventional 
synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, as initial 
therapy, followed by biologic DMARDs (tumor necrosis factor [TNF] inhibitors, 
interleukin- 12 and interleukin-23 inhibitors, and interleukin-17 inhibitors) or apremilast in 
patients who had an inadequate response to conventional synthetic DMARDs.1
The presence of anti-CCP antibodies in PsA and the prevalence was between 5.6 and 
15.7% giving the optionality of biological treatment for RA patients, identifying a predictor 
for response will acquire more attention to rheumatologists for such patients.1,2
Psoriatic arthritis is a severe form of arthritis in which deformities and joint damage develop 
in many patients. Bone erosions are observed in 47% of patients within the first 2 years, 
despite the use of traditional disease-modifying medications in more than half the patients. 
Furthermore, presence of ACCP in PsA patients consider one of bad prognostic factors for 
PsA Patients.3
7. RESEARCH QUESTION AND OBJECTIVES
ACCP have been associated with lower response in PsA patients with positive ACCP. The 
objective is to evaluate the effect of ACCP on PsA patients and effect on their response to 
biological treatment.
8. RESEARCH METHODS 
8.1. Study Design

Retrospective analysis of patients with PsA that received etanercept from Baghdad 
Teaching Hospital (Rheumatology Center) from May 2012 until August 2019
(inclusion and exclusion criteria will apply for selecting patients).

Primary objective: Determine the clinical impact of ACCP positivity for 
management (etanercept) in patients with PsA compared to negative ACCP patients.

Primary objective: Determine the clinical impact of ACCP positivity for 
management (etanercept) in patients with PsA compared to negative ACCP patients.

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8.2. Setting
Patients and Methods
Data collected from the Baghdad Teaching Hospital registry. The rheumatology patient 
registry is a prospective longitudinal multicenter cohort initiated in 2012. It captures all 
patients treated with biologic therapies managed in the rheumatology department.  The 
decision to initiate and maintain the treatment is guided by the American College of 
Rheumatology (ACR) recommendations.4
Study population
Patients will be included in the study if they meet the ACR/European League Against 
Rheumatism (EULAR) 2010 criteria for PsA3,4 with at least 1 year of follow-up after starting 
their first biologic therapy.  This includes patients who were in monotherapy or in 
combination therapy with concomitant conventional DMARDs.
Hypothesis
Our hypothesis is that there is no difference in response between sero-positive and 
sero-negative PsA patients to treatment with Enbrel.
8.2.1. Inclusion Criteria
Patients must meet all the following inclusion criteria to be eligible for inclusion in the study:
1. Diagnosed PsA patients. 
2. ≥18 years of age. 
3. Have not received previous biological treatment.
8.2.2. Exclusion Criteria
Patients meeting any of the following criteria will not be included in the study:
1. Previous use of other biological treatments.
2. Etanercept use for less than 1-year duration.
8.3. Data Sources
Patients with PsA will be identified in the rheumatology registry. Patient demographic 
information (age, gender), education level (years), present smoking status, disease duration 
(years), current MTX and steroid therapy (yes/no), baseline DAPSA (Disease Activity in 
Psoriatic Arthritis), anti-citrullinated protein antibody (ACCP) status will be obtained. 
Primary Outcomes: DAPSA in first and last follow up visit.

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8.4. Study Size
There is no pre-identified study size. All patients that meet the criteria will be entered into 
the study.
8.5. Data Management 
The structured data is exported into an Excel spreadsheet and then transferred to the SPSS
database (version 23) for statistical analysis.
8.6. Data Analysis 
Categorical covariates will be described by frequency distribution while continuous 
covariates expressed in terms of their mean and standard deviation or median and 
interquartile range as appropriate. Patients will be divided for sero-positive PsA and 
sero-negative PsA (according to ACCP status) the unadjusted comparisons between groups 
of the covariates and the outcomes are evaluated using chi2 tests for categorical data, while 
for continuous data, we used the student’s t-test for normally distributed variables and the 
Kruskall-Wallis test for non-parametric data.
We determined the effect of sero-positive on the biologic treatment response patients with 
PsA a multivariate analysis by using a stepwise linear regression model. The response 
variable is defined as disease activity index (either DAPSA, DAS-28 ESR, or DAS-28 CRP)
at last visit. The baseline variables considered demographic data, disease duration (years), 
methotrexate (yes/no), current steroid therapy (yes/no), baseline disease activity index, anti-
CCP (yes/no), psoriasis presentation and present smoking (yes/no). 
We determined the effect of response by using change from baseline in disease activity index
at the last visit.  P value <0.05 is considered statistically significant, without multiplicity 
adjustment, for this post-hoc analysis.
8.7. Quality Control
Not Applicable (NA).
8.8. Limitations of the Research Methods
The missing data that could lead to bias is an identified limitation in this study.
8.9. Other Aspects
Not Applicable (NA).
9. PROTECTION OF HUMAN SUBJECTS
9.1. Patient Information 
This study involves data that exist in anonymized structured format and contain no patient 
personal information. 

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9.2. Patient Consent
As this retrospective study involves anonymized structured data, which according to 
applicable legal requirements do not contain data subject to privacy laws, obtaining informed 
consent from patients by Pfizer is not required.
9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
Not required.
9.4. Ethical Conduct of the Study
The study conducted in accordance with legal and regulatory requirements, as well as with 
scientific purpose, value and rigor and follow generally accepted research practices described 
in Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the International 
Society for Pharmacoepidemiology (ISPE), Good Epidemiological Practice (GEP) guidelines 
issued by the International Epidemiological Association (IEA), and Good Practices for 
Outcomes Research issued by the International Society for Pharmacoeconomics and 
Outcomes Research (ISPOR).
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
This study involves data that exist as structured data by the time of study start.  In these data 
sources, individual patient data are not retrieved or validated, and it is not possible to link 
(ie, identify a potential association between) a particular product and medical event for any 
individual.  Thus, the minimum criteria for reporting an adverse event (AE) (ie, identifiable 
patient, identifiable reporter, a suspect product, and event) cannot be met.
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
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 investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of a Pfizer 
product, Pfizer should be informed immediately.  

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12. REFERENCES
1.
Laura Bogliolo, Claudia Alpini, Roberto Caporali, Carlo Alberto Scirè, Remigio 
Moratti, Carlomaurizio Montecucco. Antibodies to cyclic citrullinated peptides in 
psoriatic arthritis.The Journal of Rheumatology Mar 2005, 32 (3) 511-515.
2.
Christopher T. Ritchlin, M.D., M.P.H., Robert A. Colbert, M.D., Ph.D., and Dafna D. 
Gladman, M.D. Psoriatic Arthritis. N Engl J Med 2017; 376:957-970.
3.
Gossec L, et al. Ann Rheum Dis 2016;75:499–510. doi:10.1136/annrheumdis-2015-
208337.
4.
Coates, L.C.et al. Group for Research and Assessment of Psoriasis and Psoriatic 
Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis. Arthritis & 
Rheumatology, 2016. 68: 1060-1071.

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13. LIST OF TABLES 
NA.
14. LIST OF FIGURES
NA.
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
None.

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