Long Term Adherence and Efficacy of Etanercept in SpA Iraqi Patients: 7 Year Data From Local Registry
Conditions: Spondyloarthrosis
Sponsor: Pfizer

Etanercept
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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
Long Term Adherence and Efficacy of 
Etanercept in SpA Iraqi Patients: 7 Year 
Data From Local Registry
Protocol number
B1801414
Protocol version identifier
3.0
Date
28 July 2021
Active substance
Etanercept
Medicinal product
Etanercept
Research question and objectives
Patients' adherence to biological treatment is 
one of the key factors for better 
response. The objective of this study is to 
evaluate the long-term adherence of SpA 
patients on Enbrel and the difference in 
efficacy between adherent and nonadherent 
groups.
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.
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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................2
2. LIST OF ABBREVIATIONS................................................................................................4
3. RESPONSIBLE PARTIES....................................................................................................6
4. AMENDMENTS AND UPDATES.......................................................................................7
5. MILESTONES.......................................................................................................................8
6. RATIONALE AND BACKGROUND..................................................................................8
7. RESEARCH QUESTION AND OBJECTIVES ...................................................................8
8. RESEARCH METHODS ......................................................................................................9
8.1. Study Design .............................................................................................................9
8.2. Setting........................................................................................................................9
8.2.1. Inclusion Criteria ..........................................................................................9
8.2.2. Exclusion Criteria.......................................................................................10
8.3. Data Sources............................................................................................................10
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......................................................................11
8.9. Other Aspects ..........................................................................................................11
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................11
9.1. Patient Information..................................................................................................11
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 ......................................................................................................................12
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........12
12. REFERENCES ..................................................................................................................12
13. LIST OF TABLES.............................................................................................................14
14. LIST OF FIGURES ...........................................................................................................14
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ANNEX 1. LIST OF STAND ALONE DOCUMENTS .........................................................14
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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
ACR
American College of Rheumatology 
AE
Adverse Event
ANA
Antinuclear Antibody
AS
Ankylosing Spondylitis
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
DMARDs
Disease-modifying Antirheumatic Drugs 
EULAR
European League Against Rheumatism 
GEP
Good Epidemiological Practice
GGP
Guidelines for Good Pharmacoepidemiology 
Practices
HLA-B27
Human Leukocyte Antigen B27
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 
NIS
Non-interventional Study
NSAIDs
Nonsteroidal Anti-inflammatory Drugs
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Abbreviation
Definition
RA
Rheumatoid Arthritis
SpA
Apondyloarhtopathies 
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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
 
4. ABSTRACT
See ANNEX 1.
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5. AMENDMENTS AND UPDATES
Amendment 
number
Date
Protocol 
section(s) 
changed
Summary of amendment(s)
Reason
1
28 July 
2021
Section 4 
Abstract
Added back in to accept link
Administrative
Throughout 
Document
Spelling errors
Administrative
Section 6. 
Milestones
Updated to align with Study Report
Administrative
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6. MILESTONES
Milestone
Planned date
Start of data collection
01 September 2020
End of data collection
01 October 2020
Final study report
01 September 2021
7. RATIONALE AND BACKGROUND
Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. 
As such, it is a class or category of diseases rather than a single, specific entity.1
Non-vertebral signs and symptoms of degenerative or other not-directly-infected 
inflammation, in the manner of spondyloarthropathies, include asymmetric peripheral 
arthritis (which is distinct from rheumatoid arthritis), arthritis of the toe interphalangeal 
joints, sausage digits, Achilles tendinitis, plantar fasciitis, costochondritis, iritis, and 
mucocutaneous lesions. However, lower back pain is the most common clinical presentation 
of the causes of spondyloarthropathies; this back pain is unique because it decreases with 
activity.2  Spondyloarthropathies have an increased incidence of HLA-B27, as well as 
negative rheumatoid factor and ANA.
Ankylosing spondylitis (AS) is a type of arthritis in which there is long-term inflammation of 
the joints of the spine. Typically, the joints where the spine joins the pelvis are also affected. 
Occasionally, other joints such as the shoulders or hips are involved. Eye and bowel 
problems may also occur.  Back pain is a characteristic symptom of AS, and it often comes 
and goes. Stiffness of the affected joints generally worsens over time.3
Between 0.1% and 1.8% of people are affected with AS world wide.4 Onset is typically in 
young adults. Males are more often affected than females.4
There is no cure for ankylosing spondylitis. Treatments may improve symptoms and prevent 
worsening.  Treatments may include medication, exercise, and surgery. Medications used 
include NSAIDs, steroids, DMARDs such as sulfasalazine, and biologic agents.5
8. RESEARCH QUESTION AND OBJECTIVES
The objective of this study was to evaluate the 1 and 7 years (long-term) adherence of SpA 
patients on Enbrel and the difference in efficacy between adherent and nonadherent groups.
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9. RESEARCH METHODS
9.1. Study Design

Retrospective analysis of patients with SpA that received etanercept from Baghdad 
Teaching Hospital (Rheumatology Center) from May 2012 through August 2019.

Primary objective: 1 and 7 years adherence of SpA patients on Enbrel.

Secondary objective: The difference in efficacy between the adherent group of 
patients (who continued Enbrel treatment) and the nonadherent group.
9.2. Setting
Patients and Methods
Data was collected from the Baghdad Teaching Hospital rheumatology registry. It captured
all patients who have been treated with biologic therapies managed in the rheumatology 
department.  The decision to initiate and maintain the treatment was guided by the American 
College of Rheumatology (ACR) recommendations. 
Study population
Patients included in the study met the American College of Rheumatology/European League 
Against Rheumatism (EULAR) 2019 criteria for SpA6, with at least 1 year of follow-up after 
starting their first biologic therapy. Exclusion criteria: patients previously or currently 
treated with other biological treatments. 
Hypothesis
There was a small percentage of patients who adhered to Enbrel over 7 years, and there was
no difference between the adherent and the nonadherent group in efficacy.
9.2.1. Inclusion Criteria
Patients met all of the following inclusion criteria to be eligible for inclusion in the study:
1. Diagnosed SpA patients. 
2. 18 years of age and older. 
3. Did not receive previous other biological treatments.
4. Patients have at least 1 year on Enbrel.
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9.2.2. Exclusion Criteria
Patients meeting any of the following criteria were not included in the study:
1. Had previously used another biological treatments.
2. Use of etanercept for less than 1 year duration.
9.3. Data Sources
Patients were identified from the rheumatology patient registry with a SpA diagnosis and 
information was obtained on patient demographics (age, gender), education-level (years), 
present smoking status, disease duration (years), current MTX and steroid therapy (yes/no), 
baseline BASDAI, and BASFI and last assessment of baseline BASDAI and BASFI. 
Primary Outcomes: was the percentage of patients that have 7 year adherence on Enbrel.
9.4. Study Size
There was no pre-identified study-size sample. Patients that met the criteria were entered
into the study.
9.5. Data Management 
The structured data was exported into an Excel spreadsheet and then transferred to the SPSS 
database (version 23) for statistical analysis.
9.6. Data Analysis
All covariates will be summarized to get information about frequency distribution and mean, 
median or standard deviation. Numbers and percentages will be provided for dichotomous 
and polychotomous variables when performing descriptive analysis of categorical data. 
Means, medians, standard deviations, and interquartile range as appropriate will be provided 
for continuous variables when performing descriptive analysis of continuous data. Patients 
will be assessed for first-year adherence (first-year adherence is defined as patients having at 
least 7 consecutive visits in one year of Enbrel treatment), then the 7-year adherence will be
assessed and the percentage of patients that achieve 7-year adherence will be calculated. The 
difference between adherent and nonadherent groups in baseline visit and last visit BASDAI 
and BASFI will be assessed for both groups.
The bivariate analysis will be conducted to determine if there is any association between the 
outcome and the exposure (the covariates). Unadjusted comparisons between groups of 
covariates and outcomes will be evaluated using appropriate tests: chi-squared test will be
used for categorical variables, t-test will be used for continuous variables, and the 
Kruskal-Wallis test for non-parametric variables; p-values will be generated. The baseline 
variables considered demographic data, disease duration (years), methotrexate (yes/no), 
current steroid therapy (yes/no), present smoking (yes/no).
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The difference in efficacy between adherent and nonadherent groups by using change from
the baseline in BASDAI and BASFI at the last visit will be determined. P-value <0.05 will be
considered statistically significant, without multiplicity adjustment for this post-hoc analysis.
9.7. Quality Control
NA.
9.8. Limitations of the Research Methods
No missing data that could lead to bias was an identified limitation in this study.
9.9. Other Aspects
NA.
10. PROTECTION OF HUMAN SUBJECTS
10.1. Patient Information 
10.2. This study involved data that exist in an anonymized, structured format and do 
not contain the patient's personal information.Patient Consent
As this retrospective study involved anonymized, structured data, which according to
applicable legal requirements did not contain data subject to privacy laws, obtaining 
informed consent from patients by Pfizer was not required.  
10.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
Not required.
10.4. Ethical Conduct of the Study
The study was conducted in accordance with legal and regulatory requirements, as well as,
with scientific purpose, value, and rigor, and followed 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).
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11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
This study involved data that exist as structured data from the time of study-start.
In these data sources, individual patient data were not retrieved, or validated and was 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) could not be
met.
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
There was no event of any prohibition or restriction imposed (eg, clinical hold) by any
applicable competent authority in any area of the world. Nor was the investigator aware of 
any new information that might have influenced the evaluation of the benefits and risks of a 
Pfizer product.
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13. REFERENCES
1.
Proft, Fabian, and Denis Poddubnyy. “Ankylosing Spondylitis and Axial 
Spondyloarthritis: Recent Insights and Impact of New Classification Criteria.” 
Therapeutic Advances in Musculoskeletal Disease, June 2018, pp. 129–139.
2.
Garcia-Montoya, Leticia et al. “Recent advances in ankylosing spondylitis: 
understanding the disease and management.” F1000Research vol. 7 F1000 Faculty 
Rev-1512. 21 Sep. 2018.
3.
Jürgen Braun, Axial spondyloarthritis including ankylosing spondylitis, Rheumatology, 
Volume 57, Issue suppl_6, November 2018, Pages vi1–vi3.
4.
Dubash, Sayam, et al. “New Advances in the Understanding and Treatment of Axial 
Spondyloarthritis: From Chance to Choice.” Therapeutic Advances in Chronic Disease, 
Mar. 2018, pp. 77–87.
5.
Davide Simone, M Hussein Al Mossawi, Paul Bowness, Progress in our understanding 
of the pathogenesis of ankylosing spondylitis, Rheumatology, Volume 57, Issue 
suppl_6, November 2018, Pages vi4–vi9.
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14. LIST OF TABLES 
NA.
15. LIST OF FIGURES
NA.
ANNEX 1. LIST OF STAND ALONE DOCUMENTS
Number
Document reference 
number
Date
Title
1
Section 4
21 June 2021
Long Term Adherence and Efficacy
of Etanercept in SpA Iraqi Patients: 
7 Year Data From Local Registry
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