Characteristics and 6-month Outcomes Among Real-World Rheumatoid Arthritis Patients Initiating Inflectra
Conditions: Arthritis, Rheumatoid
Sponsor: Pfizer

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Amendment 2, Version 3.0, 24 July 2023
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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
Characteristics and 6-month Outcomes 
Among Real-World Rheumatoid Arthritis 
Patients Initiating Inflectra
Protocol number
C1231007
Protocol version identifier
3.0
Date
24 July 2023
Research question and objectives
The objectives of this study are as follows:
1. To describe the characteristics of 
patients newly initiated on Inflectra.
2. To describe 6-month outcomes after 
initiating Inflectra, among patients 
who have 6-months follow-up 
information in CorEvitas’ RA 
Registry. 
Author
, MD, RhMSUS
Pfizer Inc.
500 Arcola Road
Collegeville, PA 19426
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. ABSTRACT...........................................................................................................................7
5. AMENDMENTS AND UPDATES.......................................................................................8
6. MILESTONES.......................................................................................................................9
7. RATIONALE AND BACKGROUND..................................................................................9
8. RESEARCH QUESTION AND OBJECTIVES ...................................................................9
9. RESEARCH METHODS ......................................................................................................9
9.1. Study Design .............................................................................................................9
9.2. Setting......................................................................................................................10
9.2.1. Inclusion Criteria ........................................................................................10
9.2.2. Exclusion Criteria.......................................................................................10
9.3. Variables..................................................................................................................10
9.4. Data Sources............................................................................................................12
9.5. Study Size................................................................................................................12
9.6. Data Management ...................................................................................................13
9.7. Data Analysis ..........................................................................................................13
9.8. Quality Control........................................................................................................13
9.9. Limitations of the Research Methods......................................................................13
9.10. Other Aspects ........................................................................................................13
10. PROTECTION OF HUMAN SUBJECTS ........................................................................13
10.1. Patient Information................................................................................................13
10.2. Patient Consent......................................................................................................14
10.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............14
10.4. Ethical Conduct of the Study ................................................................................14
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................14
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........15
13. REFERENCES ..................................................................................................................16

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14. LIST OF TABLES.............................................................................................................17
15. LIST OF FIGURES ...........................................................................................................17
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.........................................................17
ANNEX 2. ADDITIONAL INFORMATION.........................................................................17

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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
CABG
coronary artery bypass grafting
CDAI
Clinical Disease Activity Index
CHF
congestive heart failure
csDMARD
conventional synthetic disease-modifying 
antirheumatic drug
CV
cardiovascular
CVD
cardiovascular disease
DAS
Disease Activity Score
DVT
deep venous thrombosis
EQ-5D-3L
3-Level version of EuroQoL-5 Dimensions
ESR
erythrocyte sedimentation rate
FDA
Food and Drug Administration
GPP
Good Pharmacoepidemiology Practice
HAQ
health assessment questionnaire
ICMJE
International Committee of Medical Journal Editors
IEC
Independent Ethics Committee
IRB
Institutional Board Review
JAK
Janus Kinase
LDA
low disease activity
mACR
modified American College of Rheumatology
MI
myocardial infarction

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Abbreviation
Definition
MTX
methotrexate
PCI
percutaneous coronary intervention
PRO
patient reported outcome
RA
rheumatoid arthritis
SAP
Statistical Analysis Plan
SJC
swollen joint count
TIA
transient ischemic attack
TJC
tender joint count
US
United States
VAS
visual analogue scale

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3. RESPONSIBLE PARTIES
Principal Investigator(s) of the Protocol
Name, degree(s)
Job Title
Affiliation
Address
, 
MD, RhMSUS
 
Pfizer Inc.
500 Arcola Road
Collegeville, PA 19426
 PharmD, 
MBA
Pfizer Inc
66 Hudson Boulevard 
East, New York New 
York 10001, US
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4. ABSTRACT
N/A.

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5. AMENDMENTS AND UPDATES
Amendment 
number
Date
Protocol 
section(s) 
changed
Summary of amendment(s)
Reason
1 administrative
18-Jul-
2022
Study 
Information
Deleted medicinal product 
and active substance and 
updated author name to new 
NIS Lead. 
Medicinal product and 
active substance are not 
applicable for this study 
type. The study was 
handed over to a new NIS 
Lead, therefore author 
information was updated. 
Section 3
Updated respsonsible parties. 
Section 3 was updated due 
to changes in the study 
team. 
Section 6
Updated study timelines
Study timelines were 
updated to reflect the 
current status. 
Section 10.3
Corrected template wording. 
This section was corrected 
as there is no IRB approval 
required for these types of 
studies. 
Section 
9.6.1 and 
9.6.2
These sections were deleted 
according to template 
instructions. 
This is a secondary 
structured data analysis 
study. Following 
instructions on the protocol 
template section 9.6.1 and 
9.6.2 were deleted.
Section 10.3
Section 10.3 was updated to 
reflect the local requirements 
for his study. 
Wording in section 10.3 
was updated, because this
secondary structured data 
collection does not need to 
apply for IRB approval 
according to local 
requirements. 
2 administrative
24 July 
2023
Section 3.
Address change
Pfizer New York 
headquaerters address 
change
Section 6.
Milestones section Planned 
Dates changed 
It is changed to match with 
Registry
Protocol 
template
Protocol template is updated
It is updated to the latest 
protocol template for 
Secondary Data Collection 
studies.

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6. MILESTONES
Milestone
Planned date
Start of data collection 
09 December 2022
End of data collection
03 February 2023
Final study report
11 October 2023
7. RATIONALE AND BACKGROUND
Rheumatoid arthritis (RA) is a chronic, immune-mediated, inflammatory disease affecting 
many joints, including those in the hands and feet. RA has a wide global presence and is 
estimated to affect 0.5 to 1% of the general population. Inflectra is 1 of 4 currently approved 
biosimilars for infliximab, approved in April 2016.1 There is a need to understand how 
biosimilars are used in the real world for rheumatoid arthritis patients (eg, attitudes/hesitancy 
about biosimilars, sequencing, issues with payers). There are also questions about how 
Inflectra is being used in the real world (eg, line of therapy, how many patients use 
originators first versus those who do not). This study will examine treatment patterns and 
effectiveness of real-world Inflectra initiators in the CorEvitas’ RA Registry.
8. RESEARCH QUESTION AND OBJECTIVES
There are 2 objectives for this study:
1. To describe the characteristics of patients newly initiated on Inflectra.
2. To describe 6-month outcomes after initiating Inflectra, among patients who have 
6-months follow-up information in the CorEvitas’ RA Registry.
9. RESEARCH METHODS 
9.1. Study Design
This is a descriptive retrospective study of RA patients initiating Inflectra from the 
CorEvitas’ Registry. Primary outcome of this study will be the achievement of low disease 
activity (LDA) (Clinical Disease Activity Index [CDAI] <10) at 6 months. Secondary 
outcomes will be the achievement of remission (CDAI <2.8), ∆ CDAI, ∆ health assessment 
questionnaire (HAQ), ∆patient pain, ∆ patient fatigue, and achievements of modified 
American College of Rheumatology (mACR)20/50/70.
For further details, please refer to the detailed Statistical Analysis Plan (SAP) included as a 
stand-alone document. 

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9.2. Setting
CorEvitas’ RA Registry is an ongoing longitudinal clinical registry that was established in 
2001. Longitudinal follow-up data is collected from both patients and their treating 
rheumatologist during routine clinical encounters using RA Registry questionnaires. The RA 
Registry has enrolled over 56,090 patients with RA. The collection of data from the RA 
Registry represents over 210,949.53 patient years of data. Structured clinical data is available 
in this Registry (eg, disease activity scores, comorbidities, imaging results, patient-reported 
outcomes data, etc) that is not available in claims databases.
9.2.1. Inclusion Criteria
Participants must meet all of the following inclusion criteria to be eligible for inclusion in the
study:
1. Be at least 18 years of age.
2. Have been diagnosed with RA by a rheumatologist. 
3. Have initiated treatment with Inflectra.
4. Had assessment of effectiveness in patients who have at least 1 follow up visit.
9.2.2. Exclusion Criteria
There are no exclusion criteria for this study.
9.3. Variables
Patient characteristics at baseline:

Age, sex, race, and ethnicity

Education

Work status

Insurance type

Smoking status and alcohol use

Body mass index

Medication use
o
Prior Medication use

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
Number of prior conventional synthetic disease-modifying 
antirheumatic drugs (csDMARDs) (not including at the time of the 
Inflectra initiation)

Concomitant therapy (none, methotrexate [MTX] only, nonMTX 
csDMARD only, MTX & nonMTX csDMARD) 

Number of prior biologics 

Prednisone use (History, Current, dose in current users)

Last therapy prior to Inflectra
o
Reason for Inflectra initiation

Number of patients with at least 1 initiation reported 

Total number of reasons

%Safety, %Efficacy, %Cost/Insurance, %Other reasons

History of Comorbidities
o
Cardiovascular disease [CVD] (myocardial infarction [MI], stroke, acute 
coronary syndrome, coronary artery disease, congestive heart failure [CHF], 
revascularization procedure including percutaneous coronary intervention 
[PCI], coronary artery bypass graft [CABG] or coronary artery stents, 
ventricular arrhythmia, cardiac arrest, unstable angina, peripheral ischemia, 
peripheral arterial disease, other cardiovascular [CV], deep venous thrombosis 
[DVT], and transient ischemic attack [TIA]) 
o
History of malignancy (lung cancer, breast cancer, lymphoma, skin cancer 
[melanoma and squamous], and other cancer) 
o
Hypertension
o
Diabetes 
o
Depression
o
Fibromyalgia
Disease activity measures:

Clinical Characteristics and Assessments

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o
Disease duration
o
Age of onset
o
Composite disease activity measures (physician derived elements)

Clinical Disease Activity Index (CDAI)

Disease Activity Score ([DAS]28, erythrocyte sedimentation rate
[ESR])

Physician global assessment of 28 joint count (tender joint count 
[TJC], swollen joint count [SJC])
o
Patient reported outcome (PRO) measures 

Health Assessment Questionnaire (HAQ) 

Pain visual analogue scale (VAS) (0-100) 

Patient global assessment VAS (0-100) 

Fatigue VAS (0-100) 

Stiffness VAS (0-100)

3-Level version of EuroQol-5 Dimensions (EQ-5D-3L)
9.4. Data Sources
This is a retrospective analysis of an existing database of patient encounters from the 
CorEvitas RA Registry.
Providers and patients complete follow-up questionnaires approximately every 6 months. 
Eligible medications are biologics, biosimilars, and Janus Kinase (JAK) inhibitors that are 
Food and Drug Administration (FDA) approved for the treatment of RA. 
9.5. Study Size
This is a descriptive, exploratory study; therefore, power calculations were not considered. 
Sample size calculations are not applicable.
As of 21 July 2021, there were approximately 235 Inflectra initiators.

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9.6. Data Management 
Stata Release 16 (StataCorp LLC, College Station TX), R Version 4.0.3 (The R Foundation 
for Statistical Computing, Vienna Austria), or SAS Version 9.4 (SAS Institute, Cary NC) 
will be used for analyses. Refer to the SAP.
9.7. Data Analysis 
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a SAP, which will be dated, filed and maintained by the sponsor. The SAP
may modify the plans outlined in the protocol; any major modifications of primary endpoint 
definitions or their analyses would be reflected in a protocol amendment.
9.8. Quality Control
Detailed quality control of the analyses will be documented in the SAP. 
9.9. Limitations of the Research Methods
The following items could potentially limit the generalizability of the results.
The RA Registry used in this research includes a sample of adults with RA that are not 
necessarily representative of all adults with RA in the United States (US) and Canada. In 
particular, these are patients with RA with clinical visits with rheumatologists. In addition, 
history of medication use prior to enrollment is derived from what is reported by patients and 
their current rheumatologist within the registry. The “cause” of visits is not captured, 
although the assumption can likely be made that the rheumatology visit is “RA related.” The 
Registry captures physician-reported prescribing, and there are no measures of patient 
adherence. Additional possible study limitations are variables with small cell counts (n<5) 
which will be suppressed to protect patient confidentiality, and 6-month outcome analyses 
will be unadjusted.
Given that this is a retrospective analysis, there are no risks in what is planned to be carried 
out in the protocol.
9.10. Other Aspects
Not Applicable.
10. PROTECTION OF HUMAN SUBJECTS
10.1. Patient Information 
This study involves data that exist in anonymized structured format and contain no patient 
personal information.

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10.2. Patient Consent
As this 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.
10.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
This is a retrospective study for which IRB approval is not required according to local 
regulations. 
10.4. Ethical Conduct of the Study
The study will be 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 the Declaration of Helsinki and that are consistent with Good 
Pharmacoepidemiology Practice (GPP)2
11. 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.

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12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
For all publications relating to the Study, Pfizer 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, 
established by the International Committee of Medical Journal Editors.
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 party responsible for collecting data 
from the participant 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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13. REFERENCES
1.
U.S. Food & Drug Administration. Biosimilar Product Information. Updated December 
27, 2021. Accessed January 10, 2022. 
https://www.fda.gov/drugs/biosimilars/biosimilar-product-information.
2.
Battisti WP, Wager E, Baltzer D, et al. Good Publication Practice for Communicating 
Company Sponsored Medical Research: GPP3. Ann Intern Med. 2015;163(6):461-4.

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14. LIST OF TABLES 
None.
15. LIST OF FIGURES
None.
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
None.
ANNEX 2. ADDITIONAL INFORMATION
Not Applicable.

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