OBSERVATIONAL, REAL WORLD STUDY OF INFLECTRA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD) IN THE UNITED STATES AND CANADA
Conditions: Inflammatory Bowel Disease (IBD), Crohn's Disease (CD), Ulcerative Colitis (UC)
Sponsor: Pfizer

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Study Information
Title
Observational, real-world study of 
INFLECTRA in patients with inflammatory 
bowel disease (IBD) in the United States and 
Canada
Protocol number
C1231006
Protocol version identifier
3.0
Date of last version of protocol
26 January 2018
EU Post Authorisation Study (PAS) 
register number
EUPAS22444
Medicinal product
CT-P13 (INFLECTRA®/infliximab-dyyb) 
Research question and objectives
Primary Objective
1. To describe drug use patterns,
treatment adherence and associated 
costs in adult UC and CD cohorts
treated with INFLECTRA in a real-
world setting.
Secondary Objectives
2. To assess real-world clinical and 
economic outcomes related to 
disease severity in adult UC and CD 
cohorts who initiated therapy with 
INFLECTRA as their first biologic, 
switched to INFLECTRA from 
REMICADE or, switched to 
INFLECTRA from another biologic.
3. To assess real-world patient reported 
quality of life in both the UC and CD 
cohorts who initiated therapy with 
INFLECTRA as their first biologic, 
switched to INFLECTRA from 
REMICADE or, switched to 
INFLECTRA from another biologic.
4. To describe the demographic and 
clinical characteristics of patients 
receiving INFLECTRA for the 
treatment of UC and CD.
5. To assess healthcare resource 
utilization and indirect costs in adult 
patients receiving INFLECTRA for 
the treatment of UC or CD patients 
receiving INFLECTRA for 
Ulcerative Colitis or Crohn’s 

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TABLE OF CONTENTS
1. LIST OF ABBREVIATIONS................................................................................................5
2. RESPONSIBLE PARTIES....................................................................................................6
3. ABSTRACT...........................................................................................................................7
4. AMENDMENTS AND UPDATES.....................................................................................11
5. MILESTONES.....................................................................................................................12
6. RATIONALE AND BACKGROUND................................................................................12
7. RESEARCH QUESTION AND OBJECTIVES .................................................................14
7.1. Primary Objective ...................................................................................................14
7.2. Secondary Objectives..............................................................................................14
8. RESEARCH METHODS ....................................................................................................14
8.1. Study Design ...........................................................................................................14
8.2. Setting......................................................................................................................15
8.2.1. Site Selection and Physician Inclusion and Exclusion Criteria..................15
8.2.2. Study Population.........................................................................................16
8.2.3. Inclusion Criteria ........................................................................................17
8.2.4. Exclusion Criteria.......................................................................................18
8.2.5. Study Procedures ........................................................................................18
8.3. Variables..................................................................................................................19
8.3.1. Baseline Characteristics/Disease Variables................................................19
8.3.2. Outcomes/Endpoint Variables....................................................................20
8.3.3. Exposure/Independent Variables of Interest...............................................22
8.3.4. Other Covariates/Control Variables ...........................................................22
8.4. Data Sources............................................................................................................23
8.5. Study Size................................................................................................................23
8.6. Data Management ...................................................................................................24
8.7. Data Analysis ..........................................................................................................25
8.7.1. Outcome Endpoints ....................................................................................25
8.7.2. Statistical Software.....................................................................................28
8.8. Quality Control........................................................................................................28
8.9. Limitations of the Research Methods......................................................................29
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8.10. Other Aspects ........................................................................................................29
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................29
9.1. Patient Information and Consent.............................................................................29
9.2. Patient Withdrawal..................................................................................................30
9.3. Institutional Review Board/Independent Ethics Committee...................................30
9.4. Ethical Conduct of the Study ..................................................................................30
9.5. Single Reference Safety Document.........................................................................30
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................32
10.1. Single Reference Safety Document.......................................................................39
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........39
12. REFERENCES ..................................................................................................................41
13. LIST OF TABLES.............................................................................................................43
14. LIST OF FIGURES ...........................................................................................................43
ANNEX 1. LIST OF STAND ALONE DOCUMENTS .........................................................44
14.1. Partial Mayo Questionnaire*.................................................................................44
14.2. Harvey-Bradshaw Index for Patients with Crohn’s Disease.................................45
14.3. Quality of Life Assessment Using Visual Analog Scale (VAS)...........................46
14.4. Short Inflammatory Bowel Disease Questionnaire...............................................47
14.5. Work Productivity and Activity Impairment Assessment.....................................50
14.6. Treatment Satisfaction Questionnaire ...................................................................52
14.7. Health Care Resource Utilization Questionnaire ..................................................55
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1. LIST OF ABBREVIATIONS
Table 1.
List of Abbreviations
AE
Adverse event
AEM
Adverse event monitoring
ANOVA
Analysis of variance
CD
Crohn's disease
CDAI
Crohn's disease activity index
CRF
case report form
CRP
C-reactive Protein
ED
Emergency department
EMEA
European Medicines Agency
ESR
Erythrocyte sedimentation rate
FDA
Food and Drug Administration
IBD
Inflammatory bowel disease
NIS
Non-interventional study
pMAYO
partial MAYO score
SAE
Serious Adverse event
SIBDQ
short inflammatory bowel disease questionnaire
TNF-α
Tumor Necrosis Factor-alpha
TSQM
Treatment Satisfaction Questionnaire for Medication
UC
Ulcerative Colitis
VAS
Visual Analog Scale
WPAI
Work and Productivity and Activity Impairment
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3. ABSTRACT
Title
Observational, real-world study of INFLECTRA in patients with inflammatory bowel disease 
(IBD) in the United States and Canada; Version 3.0; 25 January 2018; 
, 
MD. MSc. MPH, 
, Pfizer, Inc.
Rationale and Background
In September 2013 CT-P13 (infliximab-dyyb), the first biosimilar in the class of TNF-α 
therapies, was approved in Europe, and marketed as REMSIMA® and INFLECTRA.® The 
biosimilar was approved for use based on clinical trials conducted in Rheumatoid Arthritis 
and Ankylosing Spondylitis.  This European approval was extended to all of the other 
indications for which the originator product, REMICADE® (infliximab) was approved, based 
on the concept of extrapolation.1 The European Medicines Agency concluded that 
extrapolation of clinical efficacy and safety profile data to other indications of the originator 
product, not specifically studied during the clinical development of the biosimilar was
possible based on the overall evidence of comparability provided from the comparability 
exercise and included adequate justification that the products did not differ in a clinically 
meaningful manner. In response to concern from gastroenterologists on the lack of clinical 
data supporting the utilization of INFLECTRA in patients with inflammatory bowel disease 
(Crohn’s disease [CD] and ulcerative colitis [UC]),2 researchers in Europe and Asia initiated 
prospective and retrospective studies to collect real world data on the use of INFLECTRA in 
patients with inflammatory bowel disease (IBD).3-9 The published results of these studies 
showed that there was no difference in the safety and efficacy between the originator and the 
biosimilar. 
In April 2016, INFLECTRA, was approved by the FDA for the following indications:10
•
adult patients and pediatric patients (ages six years and older) with moderately to 
severely active Crohn’s disease who have had an inadequate response to conventional 
therapy;
•
adult patients with moderately to severely active ulcerative colitis who have had an 
inadequate response to conventional therapy;
•
patients with moderately to severely active rheumatoid arthritis in combination with 
methotrexate;
•
patients with active ankylosing spondylitis (arthritis of the spine);
•
patients with active psoriatic arthritis;
•
adult patients with chronic severe plaque psoriasis.
To date, there has been no real world data published on the use of INFLECTRA in the US 
population. 
PPD
PPD

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Study Size
This study will involve 30-40 clinical sites and recruit up to 300 patients, with a minimum of
100 patients in each cohort diagnosed with ulcerative colitis or Crohn’s disease.
Data Analysis
This study will be primarily descriptive in nature.  All categorical endpoints will be
summarized using both the number and percentage in each category.  Continuous endpoints 
will be summarized in the form of means, standard deviation (SD), median, interquartile 
ranges (IQR) and range; a 95% confidence interval (CI) for the mean will also be computed.  
Pearson’s chi-squared tests will be used for bivariate statistical testing of categorical and 
ordinal outcomes.  Student’s t-tests or 1-way ANOVA will be used for comparisons of
continuous outcomes.  For highly skewed, non-normally distributed endpoints or sample sizes 
under 30 in either group, non-parametric Wilcoxon rank-sum test will be applied.  All inferences 
will be made assuming a two-sided test with an alpha of 0.05 without adjustment for 
multiplicity.  Approaches to controlling for baseline differences between groups such as 
inverse probability weights may be considered.
Milestones
Milestone
Planned date
Start of data collection
01 Feb 2018
End of data collection 
30 Jun 2019
Registration in the EU PAS register
29 Jan 2018
Final study report
09 Sep 2019

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4. AMENDMENTS AND UPDATES
Amendment 
number
Date
Substantial or 
administrative 
amendment
Protocol 
section(s) 
changed
Summary of 
amendment(s)
Reason
1
18-Oct-2017
Administrative
Several
Minor textual changes 
plus addition of 
outcome measure.
KOL/Study team review
2
25-Jan-2018
Substantial
Several
Voluntary PASS 
designation.
Additional textual 
clarification.
ENAC and EUQPPV 
Review
3
09- Sep-2020
Administrative
Several
Additional text for 
sample size and 
recruitment
Changes in description 
of sample size and 
recruitment strategy

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5. MILESTONES
Milestone
Planned date
Start of data collection
01 Feb 2018
End of data collection 
30 Jun 2019
Registration in the EU PAS register
29 Jan 2018
Final study report
09 Sep 2019
6. RATIONALE AND BACKGROUND
REMICADE® (infliximab) is monoclonal antibody in a class of drugs referred to as 
anti-tumor necrosis factor alpha (TNF-α).  It was initially approved in the United States in 
August 1998 for the treatment of Crohn’s disease (CD),11 in November 1999 for the 
treatment of rheumatoid arthritis (RA),12 and September 2005 for the treatment of ulcerative 
colitis (UC).13 In 2011, Remicade was approved for use in pediatric forms of Crohn’s 
disease and ulcerative colitis.  It is also approved for treatment of ankylosing spondylitis, 
psoriatic arthritis, and plaque psoriasis.13
In September 2013 CT-P13 (infliximab-dyyb), the first biosimilar in the class of TNF-α 
therapies, was approved in Europe, and marketed as REMSIMA® and INFLECTRA.® The 
biosimilar was approved for use based on clinical trials conducted in Rheumatoid Arthritis 
and Ankylosing Spondylitis.  This approval was extended to all of the other indications for 
which the originator product, REMICADE® (infliximab) was approved, based on the concept 
of extrapolation1 The European Medicines Agency concluded that extrapolation of clinical 
efficacy and safety profile data to other indications of the originator product, not specifically 
studied during the clinical development of the biosimilar was possible based on the overall 
evidence of comparability provided from the comparability exercise and included adequate 
justification that the products did not differ in a clinically meaningful manner..  In response 
to concern from gastroenterologists on the lack of clinical data supporting the utilization of 
INFLECTRA in patients with inflammatory bowel disease (Crohn’s disease [CD] and 
ulcerative colitis [UC]),2 researchers in Europe and Asia initiated prospective and 
retrospective studies to collect real world data on the use of INFLECTRA in patients with 
inflammatory bowel disease (IBD).3-9 The published results of these studies reported no 
significant difference in the safety and efficacy between the originator and the biosimilar. 
In Hungary, Gecse et al4 conducted a prospective, nationwide, multicenter observational
cohort study of 210 consecutively enrolled patients with IBD (n=126 UC, n=84 UC) 
initiating treatment with INFLECTRA.  At week 14, 81.4% of CD and 77.6% of UC patients 
showed a clinical response and 53.6% of CD and 58.6% of UC patients were in clinical 
remission.  Clinical remission rates at week 14 were significantly higher in CD and UC 
patients who were infliximab naïve, compared with those with previous exposure to the 
Remicade [p < 0.05].  Adverse events were reported in 17.1% of all patients through 
week 30.  Infusion reactions and infectious adverse events occurred in 6.7% and 5.7% of all 
patients, respectively.

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In the Netherlands, Smits et al8 conducted a prospective observational cohort study of 
83 patients with IBD (57 CD, 24 UC, 2 IBD-Undefined).  The median change in disease 
activity (Harvey-Bradshaw Index) was 0 for CD and 0 for UC/IBD-U.  Median CRP and 
FCP levels did not change significantly during follow-up.  The median infliximab trough 
level increased from 3.5 ­g/ml [range 0–18] to 4.2 ­g/ml [range 0–21] at 
week 16 [p = 0.010].  Two patients developed a new detectable anti-drug antibody (ADA) 
response during follow-up and 5 patients discontinued INFLECTRA.  No serious adverse 
events occurred.
In Norway, Jorgensen et al.14 conducted randomized, non-inferiority, double-blind phase 
4 trial with 52 weeks of follow up (NOR-SWITCH).  Patients who enrolled in the study were 
randomized to remain on infliximab or switch CT-P13.  A total of 482 patients enrolled 
(241 to infliximab, 241 to CT-P13).  Patients had a mix of autoimmune diseases
(32% Crohn’s disease, 19% ulcerative colitis, 16% ankylosing spondylitis, 16% rheumatoid 
arthritis, 7% chronic plaque psoriasis 6% psoriatic arthritis).  Disease worsening occurred in 
26% of the infliximab group, and 30% in the CT-P13 group (per-protocol set; adjusted 
treatment difference −4·4%, 95% CI −12·7 to 3·9).  The frequency of adverse events was
similar between groups (for serious adverse events, 24 (10%) for infliximab 
originator vs 21 [9%] for CT-P13.  The NOR-SWITCH trial showed that switching from 
infliximab to CT-P13 was not inferior to continued treatment with infliximab. 
In April 2016, INFLECTRA, was approved by the FDA for the following indications:10
•
adult patients and pediatric patients (ages six years and older) with moderately to 
severely active Crohn’s disease who have had an inadequate response to conventional 
therapy;
•
adult patients with moderately to severely active ulcerative colitis who have had an 
inadequate response to conventional therapy;
•
patients with moderately to severely active rheumatoid arthritis in combination with 
methotrexate;
•
patients with active ankylosing spondylitis (arthritis of the spine);
•
patients with active psoriatic arthritis;
•
adult patients with chronic severe plaque psoriasis.
To date, there has been no real world data published on the use of INFLECTRA in the US 
population. 
This non-interventional study is designated as a Post-Authorisation Safety Study (PASS) and 
is conducted voluntarily by Pfizer.

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Figure 1.
Study Design
Clinical information will be recorded in the patients chart during each treatment/clinical visit.  
Data entry into the EDC system will occur quarterly, along with the administration of PROs.  
Patients who discontinue treatment before the end of the study will be followed for the full 
duration of the study.  Data collected on patients with CD and UC may be analyzed 
separately. 
8.2. Setting
8.2.1. Site Selection and Physician Inclusion and Exclusion Criteria
A geographically dispersed sample of physicians will be screened based on pre-defined 
eligibility criteria and recruited from a list of physicians for each specialty.  These physicians 
will then be asked to complete a self-administered survey questionnaire to describe the types 
of patients within their practice (eg, total caseload, estimated number of patients with each 
disease, estimated number of patients diagnosed by year).  These physicians (and/or their 
assigned staff) will also be responsible for abstracting clinical data from patient records, 
collecting patient completed questionnaires, and data entry into the case report form.  
Physician inclusion and exclusion criteria are described below:
Study Procedures

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Physician Inclusion Criteria

Certified to practice in the United States or Canada;

Must agree to study rules including resolution of data queries including missing data;

Routinely uses standard lab testing to monitor patient health;

Access to certified laboratory for basic lab testing;

Available medical records and proper documentation for patients.
Physician Exclusion Criteria

Unwilling or unable to follow study procedures;

Unwilling to prescribe biosimilars;
8.2.2. Study Population
This is an observational study; therefore the decision to treat a patient with INFLECTRA 
must be made prior to a decision to enroll them in this study.  Patients are eligible to 
participate if they have:

Initiated therapy with INFLECTRA as their first biologic;

Switched to INFLECTRA while in remission on a stable dose of REMICADE; or,

Switched to INFLECTRA from another biologic, due to non-responsiveness, 
intolerance, or other reasons.

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Figure 2.
Distribution of Eligible Patients
8.2.3. Inclusion Criteria
Patients must meet all of the following criteria to be eligible for inclusion in the study:
1. Patients with confirmed diagnosis of Ulcerative Colitis or Crohn’s Disease.
2. Evidence of a personally signed and dated informed consent document indicating that 
the patient has been informed of all pertinent aspects of the study.
3. Patient eligible to receive INFLECTRA for the treatment of their disease per 
approved drug label (patients with fistula, or stoma are eligible).

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8.2.4. Exclusion Criteria
Patients meeting any of the following criteria will not be included in the study:
1. Patient age less than 18 years at the time of consent.
2. Patient previously failed treatment with REMICADE or INFLECTRA/CT-P13.
3. Any reported contraindications for INFLECTRA/CT-P13 or REMICADE.
4. Known hypersensitivity (including severe, acute infusion reactions) to infliximab, its 
excipients or other murine proteins, at the time of enrolment.
5. Patients with communication difficulties in reading or understanding the study 
consent or questionnaires
8.2.5. Study Procedures
In this study, recruited physicians and/or their assigned staff will be responsible for patient 
identification, qualification and selection, patient interview, exam recording, data abstraction 
and completion of the patient case report form (CRF), which is described in greater detail 
below. 
During the baseline visit, the following procedures will be carried out: 

Verification of eligibility criteria;

Record demographic data, medical history, and prior disease specific concomitant 
medications (minimum of 12 months, unless newly diagnosed);

Record consumption of cigarettes/nicotine products;

Administration of baseline questionnaires;

Completion of clinical assessments;

Document adverse events (AE) and serious adverse events (SAEs), if applicable;

Patient summary and disposition.
If any abnormalities are detected during the assessments, the medical practitioner will 
communicate the results to the patient.  The medical practitioner will manage and treat the 
detected abnormality as per routine clinical practice.  Sponsor will not fund any additional 
diagnostic procedures or treatment related to the detected abnormalities.
There are no protocol required medical procedures for this study.  Lab tests are not required,
but if recent test results are available, they should be provided in the CRF.  While there are 
no required study visits, there are multiple patient reported questionnaires, depending on 
indication that should be completed at various time points (approximately) during the study 
(Table 2).

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Table 2.
Planned Schedule of Events
Procedure
Visit 
1 (Baseline)
Visit 2
Visit 3
Visit 4
Unscheduled 
visit
Day 0
Day 90
(±30 days)
Day 
180 (±30 days)
Day 365
(±30 days)
N/A
Informed 
Consent
X
Patient baseline 
characteristics
X
Disease History
X
Safety 
Information
X
X
X
X
X
Disease-related 
Resource Use
X
X
X
X
Clinical 
Outcomes
X
X
X
X
Treatment 
Details
X
X
X
X
Physician 
Information
X
Note: Patients typically receive infusions every 8 weeks, hence this study provides a 60 day 
window assuming the visit might occur within this window. All visits will be as per the 
participating physicians clinical care routine, and no visits are mandated by this study.
8.3. Variables
The following tables describe key study variables collected within this study.
8.3.1. Baseline Characteristics/Disease Variables
Table 3.
Patient Baseline Characteristics
Variable
Cohort
Operational Definition
Age
UC, CD
Patient age at baseline
Sex
UC, CD
Female/Male
Race/ethnicity
UC, CD
Hispanic or Latino/Not Hispanic or Latino; 
American Indian or Alaska Native; Asian; Black or 
African American; Native Hawaiian or Other 
Pacific Islander; White; Other
Height
UC, CD
Height in meters/Height in inches
Weight
UC, CD
Weight in Kilograms/Weight in Pounds
Body Mass Index
UC, CD
(Weight in Kilograms/[Height in Meters x Height in 
Meters]) OR (Weight in Pounds/[Height in inches x 
Height in inches]) x 703

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8.3.3. Exposure/Independent Variables of Interest
Table 8.
Treatment Details
Variable
Cohort
Operational Definition
Prescribed Drugs
UC, CD
Generic name of prescribed drug
Treatment Start Date
UC, CD
Date of first biologic dose
Infusion Start Time
UC, CD
Time infusion was started
Infusion Stop Time
UC, CD
Time infusion was stopped
Treatment End Date
UC, CD
Date of last dose, date of prescription + days’ 
supply
Treatment Dose
UC, CD
Total mg/kg at each infusion
Treatment Dose 
Adjustment
UC, CD
Dosage, date, and rationale 
Treatment 
Switch/discontinuation
UC, CD
Yes/No
Treatment
Switch/discontinuation 
Reason
UC, CD
Defined list (Lack of response, Lack of 
tolerability,
Chance in Insurance coverage, Patient 
Preference, 
Dosing schedule, Other-Specify)
Abbreviations: UC, Ulcerative Colitis; CD, Crohn’s Disease.
8.3.4. Other Covariates/Control Variables
Table 9.
Physician Information
Variable
Operational Definition
Gender
Physician gender
Age Group
Physician age group during observation window
Practice Type
Solo, group, hospital
Hospital Type
Academic, Community (general, regional, private)
Practice Location
Urban, Rural
Practice Geography
North, South, Midwest, West
Practice Size
Number of Physicians in Practice
Years in Practice
Observation Window-Physician Graduation date
Board Certification
Yes/No, Certification Description
Staff Size
Number of nurses/staff
Onsite Infusion
Yes/No
Patient Caseload
Total number of patients meeting inclusion/exclusion criteria
Patient on Therapy 
Caseload
Total number of patients meeting inclusion/exclusion criteria
Treatment 
Guidelines/Protocols
Yes/No

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8.4. Data Sources 
Patient interviews and data collection will be performed by site physicians and/or their 
assigned staff.  Recruited physicians and/or their assigned staff will be responsible for patient 
identification, qualification and selection, patient interview, exam taking, data abstraction, 
and completion of the patient CRF. 
Physicians and/or site staff will be instructed to assign a unique identifier for each patient 
enrolled in the study to facilitate follow-up on data queries and for data validation.  Patient 
data will be de-identified and will be reported in aggregate.  Patient clinical data should be 
abstracted from the patient’s medical chart, or in the case of the patient reported outcome 
measures, from the assessment tools themselves, which will serve as the source document.  
No other source documents will be provided. 
Clinical data will be collected in electronic form by the participating physician or in 
collaboration with the designated site personnel.  Physicians will be provided with written 
handouts/instructions and will be periodically contacted, at least monthly until completion 
and submission of all the forms. Completed forms will be thoroughly reviewed and coded 
after entry into the database.
At least 30% of the completed forms will be randomly selected for validations against the 
source document on key CRF data points such as informed consent date, diagnosis, safety 
events, and clinical outcomes etc. by clinical research associates (CRAs).  In addition, data 
validation will include frequency counts, arrays, and distributions, running descriptive 
statistics on continuous variables, and 100% computer logic checks. Any outliers and/or 
missing data will be directly resolved with the participating physicians.
8.5. Study Size
The primary objective for this study is descriptive in nature.  As such, precision estimates 
(PEs) have been provided at the 95% confidence level, in lieu of power calculations. 
Table 10.
Sample Size for Different Precision Levels (Assuming 95% Confidence 
Level)
Sample Size for Precision of:
Percent of patients with a given risk factor
±1%
±2.5%
±5%
±10%
90%
3458
554
139
35
70%
8068
1291
323
81
50%
9604
1537
385
97
The enrollment of new patients was stopped before reaching the minimum sample size 
(N = 139) determined to be necessary. The primary reason for discontinuing recruitment was 
lack of formulary availability/insurance coverage of infliximab-dyyb during patient 
enrollment. Due to the lack of uptake of biosimilars/Inflectra in the US, fewer study sites 
than planned were able to identify and recruit patients because infliximab-dyyb was not on 
their formulary or patient insurance would not cover infliximab-dyyb. To resolve this issue, 

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the patient enrollment timeframe was extended one year beyond the planned enrollment time, 
and even with this extension, the study only reached 118 patients. The final analytical 
sample included 115 patients after excluding 1 patient due to not meeting inclusion criteria 
and 2 additional patients because they did not receive infliximab-dyyb due to being given RP 
infliximab at their infusion center/pharmacy.
8.6. Data Management 
As used in this protocol, the term case report form (CRF) should be understood to refer to an 
electronic data record.  Patient completed questionnaires will provided in paper form to the 
patients and the data will be transcribed into the CRF.  Site staff will be required to archive 
all original paper questionnaires in the local site file.
A CRF is required and should be completed for each enrolled patient.  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 investigator has ultimate responsibility for the accuracy, authenticity, and timely 
collection and reporting of all clinical, safety, laboratory data entered on the CRFs and any 
other data collection forms.  The CRFs must be signed by the investigator 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 patient’s 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 investigator’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.
Upon completion of final analyses, a clean, de-identified database will be delivered to Pfizer 
in the Pfizer preferred format, typically SAS.
Data cleaning, validations, and database lock will be conducted prior to the statistical 
analyses.
Data validations include 30% of completed CRFs being randomly selected to have 
predetermined key data points validated directly with participating physicians against the 
source document, and 100% machine checks, reporting of the proportion of missing data at 
the item/individual variable level, examination of frequencies and distributions, as well as the 
generation of descriptive statistics.
Missing data for information documented within the medical record will be rare because of 
the rigorous data collection and validation procedures that will be employed.  Any missing or 
illegible data on any CRF will result in contacting the physician directly and submitting the 
form for validation of the missing data against the patient’s medical chart.  However, certain 

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information may not be available in charts, in which case it will be described as unknown/ 
missing. 
All work will be subject to quality control and documentation procedures, to make certain the 
report is accurate and thorough, and the analyses can be reproduced.
8.7. Data Analysis 
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a Statistical Analysis Plan (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.
This study will be primarily descriptive in nature.  All categorical endpoints will be
summarized using both the number and percentage in each category.  Continuous endpoints 
will be summarized in the form of means, standard deviation (SD), median, interquartile 
ranges (IQR) and range; a 95% confidence interval (CI) for the mean will also be computed.  
Pearson’s chi-squared tests will be used for bivariate statistical testing of categorical and 
ordinal outcomes.  Student’s t-tests or 1-way ANOVA will be used for comparisons of
continuous outcomes.  For highly skewed, non-normally distributed endpoints or sample
sizes under 30 in either group, non-parametric Wilcoxon rank-sum test will be applied.  
Analyses will be made assuming a two-sided test with an alpha of 0.05 without adjustment 
for multiplicity.  Approaches to controlling for baseline differences between groups such as 
inverse probability weights may be considered.  Key statistical analysis will include: 

Proportion of patients adhering to treatment regimen;

Proportion of patients who change dosing/schedule;

Proportion of patient who discontinue treatment and rational;

Duration of steroid free remission;

Treatment related costs / healthcare resource use across the different groups

Proportion of patient remaining in clinical remission at different time points;

Reduction in steroid use will be computed.
1.1.1. Outcome Endpoints
The tables below summarize the key endpoints that will be evaluated for each objective

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Table 11.
Clinical Response Outcome Endpoints
Indication
Definition
Crohn’s disease (remission)
Harvey-Bradshaw Index score <515
Ulcerative colitis (remission)
partial Mayo score <3 points4,16
Crohn’s disease (response)
Reduction of Harvey-Bradshaw Score of ≥3 points 
from17 baseline
Ulcerative colitis (response)
Reduction of partial Mayo score of ≥3 points from 
baseline4,16
Table 12.
Patient Reported Outcome Endpoints
Indication
Definition
Crohn’s Disease
Change in Short Inflammatory Bowel Disease Questionnaire 
(SIBDQ) from baseline
Ulcerative Colitis
Change in Short Inflammatory Bowel Disease Questionnaire 
(SIBDQ) from baseline
All indications
Change in Quality of Life Visual Analog Scale (VAS), from 
baseline
Table 13.
Safety Related Outcomes for Economic Assessment
Endpoint
Definition
All Infections
Count and percentage of patients with any reported 
infection, to be used for estimating associated costs
All Serious Infections
Count and percentage of patients with any reported 
infection meeting SAE criteria, to be used for estimating 
associated costs
Malignancy and lymphoma
Count and percentage of patients with any reported 
malignancies or lymphomas, to be used for estimating 
associated costs
Infusion-related reactions
Count and percentage of patients with reported 
infusion-related reactions (Acute and other), to be used 
for estimating associated costs
Serious Adverse Events
Count of any adverse event that means seriousness 
criteria, to be used for estimating associated costs
Abbreviations: SAE, Serious Adverse Events.

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Table 16.
Patient Satisfaction and Resource Utilization Outcome Endpoints
Endpoint
Definition
WPAI
Change from baseline in WPAI score
TSQ
Average score for treatment satisfaction score at each 
time point
Healthcare Resource 
Utilization
Count of health care related visits at each time point, 
including hospitalizations, ED visits, office visits, 
infusion clinic visits
Abbreviations; WPAI, Work Productivity and Activity Index; TSQM, Treatment Satisfaction Questionnaire; 
ED, Emergency Department.
8.7.1. Statistical Software
Data analysis will be undertaken using SAS/STAT software, version 9.4 of the SAS® system 
for Windows (Cary, NC, USA).
8.8. Quality Control
As mentioned in data management, data validations include 30% of completed CRFs being 
randomly selected to have predetermined key data points validated directly with participating 
physicians against the source document, and 100% machine checks, reporting of the 
proportion of missing data at the item/individual variable level, examination of frequencies 
and distributions, as well as the generation of descriptive statistics.
Additionally, to ensure programming quality and accuracy, the following steps will be taken:

Methodology review: all methodology, from sample selection to variable 
calculation, will be discussed and reviewed at the time of SAP drafting.

Variable creation: all proposed variable definitions will be reviewed by the principal 
SAS programmer and a senior SAS developer.

Statistical review: statistical methods will be reviewed by a Pharmerit senior 
statistician as well as the Pharmerit SAS statistical programmer, project manager and 
senior scientific leader.

Output review: SAS output will be initially reviewed by the SAS programmer for 
logic and reasonability.  Output will then be reviewed by the project manager and 
senior scientific leader.  Additional reports will be run by the SAS programmer, as 
needed, to ensure validation of SAS output.  Patient counts will be verified for 
consistency with the expected counts when defining the cohort. 

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8.9. Limitations of the Research Methods
Treatment patterns, and outcomes measured within this study represent only the practices of 
physicians who have agreed to participate in this study, and may vary from non-responding 
physicians, ie, those who refused study participation, or failed to complete the study 
requirements on time and were excluded from the study, or who were unresponsive to the 
screening invitation.
Though efforts are made to ensure physician/patient inclusion/exclusion criteria are based on 
random selection, there are, nevertheless, risks of selection bias.
By abstracting patient lab results done prior to the infusion visit it may not reflect their 
current lab test results accurately.  Test done in different ways that are not standardized may 
also vary the quality of lab test.
Not all patient characteristics will be included in the data collection (eg, income and other 
variables which may influence physician-prescribing behavior or treatment decisions) and 
cannot be accounted for in the descriptive or multivariate analyses.
Information collected on the physician survey will include best estimates of patients’ 
treatment patterns but does not equate with a complete, detailed examination and analysis of 
all potential at-risk or diagnosed patient records at each physician’s site/practice.  Although 
physicians seek to record all patient experiences through examination and review of the 
medical charts, there may be some undercounting of events that are unknown to physicians, 
which may have occurred outside the office and are therefore under-represented.  This may
also refer to AEs.  It has to be expected that not all non-serious AEs will be documented in 
patient charts.  Furthermore, information regarding hospitalizations, ER visits, or any 
associated healthcare resource utilization may or may not be documented within the chart.  
Given this, healthcare resource utilization in particular is likely to be underestimated 
particularly in physicians who practice in a fully outpatient setting.
Because of the nature of this observational study, all clinical outcomes could be influenced 
by measurement error.
8.10. Other Aspects
Not Applicable.
9. PROTECTION OF HUMAN SUBJECTS
9.1. Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names 
on any sponsor forms, reports, publications, or in any other disclosures, except where
required by law. In case of data transfer, Pfizer will maintain high standards of 
confidentiality and protection of patient personal data.
The informed consent form must be in compliance with local regulatory requirements and 
legal requirements.

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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 institutional review board 
(IRB)/independent ethics committee (IEC) and Pfizer before use.
The investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study and possible risks associated with participation.  The investigator, or a 
person designated by the investigator, will obtain written informed consent from each patient
before any study-specific activity is performed. The investigator will retain the original of 
each patient's signed consent form.
9.2. Patient Withdrawal
Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, 
or administrative reasons.  In any circumstance, every effort should be made to document 
subject outcome, if possible.  The investigator should inquire about the reason for withdrawal 
and follow-up with the subject regarding any unresolved adverse events. 
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
9.3. Institutional Review Board/Independent Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, and informed consent forms, and other relevant documents, 
(eg, recruitment advertisements), if applicable, from the IRB/IEC.  All correspondence with 
the IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should 
be forwarded to Pfizer.
9.4. 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 Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE), and FDA Guidance for Industry: 
Good Pharmacovigilance and Pharmacoepidemiologic Assessment, management and 
REPORTING of adverse events/adverse reactions and All ICH/GCP guidelines. 
9.5. Single Reference Safety Document
The FDA Approved product label will serve as the single reference safety document during 
the course of the study, which will be used by Pfizer safety to assess any safety events 
reported to Pfizer Safety by the investigator during the course of this study.  The SRSD 
should be used by the investigator for prescribing purposes and guidance.

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This study protocol requires human review of patient-level unstructured data; unstructured 
data refer to verbatim medical data, including text-based descriptions and visual depictions of 
medical information, such as medical records, images of physician notes, neurological scans, 
X-rays, or narrative fields in a database.  The reviewer is obligated to report adverse events 
(AE) with explicit attribution to any Pfizer drug that appear in the reviewed information
(defined per the patient population and study period specified in the protocol).  Explicit 
attribution is not inferred by a temporal relationship between drug administration and an AE, 
but must be based on a definite statement of causality by a healthcare provider linking drug 
administration to the AE.
The requirements for reporting safety events on the non-interventional study (NIS) adverse 
event monitoring (AEM) Report Form to Pfizer Safety are as follows:

All serious and non-serious AEs with explicit attribution to any Pfizer drug that 
appear in the reviewed information by the investigator must be recorded on the case 
report form (CRF) and reported, within 24 hours of awareness, to Pfizer Safety using 
the NIS AEM Report Form.

Scenarios involving drug exposure, including exposure during pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation, lack of 
efficacy and occupational exposure associated with the use of a Pfizer product must 
be reported, within 24 hours of awareness, to Pfizer Safety using the NIS AEM 
Report Form.
For these safety events with an explicit attribution to or associated with use of, respectively, a 
Pfizer product, the data captured in the medical record will constitute all clinical information 
known regarding these adverse events.  No follow-up on related adverse events will be 
conducted.
All research staff members will complete the Pfizer requirements regarding training on the 
following: “Your Reporting Responsibilities: Monitoring the Safety, Performance and 
Quality of Pfizer Products (Multiple Languages)” and any relevant Your Reporting 
Responsibilities supplemental training. This training will be provided to all research staff 
members prior to study start.  All trainings include a “Confirmation of Training Certificate” 
(for signature by the trainee) as a record of completion of the training, which must be kept in 
a retrievable format.  Copies of all signed training certificates must be provided to Pfizer. 

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For safety events that are considered serious or that are identified in the far right column of 
the table above that are reportable to Pfizer within 24 hours of awareness, the investigator is
obligated to pursue and to provide any additional information to Pfizer in accordance with 
this 24-hour timeframe.  In addition, an investigator may be requested by Pfizer to obtain 
specific follow-up information in an expedited fashion.  This information is more detailed 
than that recorded on the case report form.  In general, this will include a description of the 
adverse event in sufficient detail to allow for a complete medical assessment of the case and 
independent determination of possible causality.  Any information relevant to the event, such 
as concomitant medications and illnesses must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative.
Reporting Period 
For each patient, the safety event reporting period begins at the time of the patient’s informed 
consent if s/he is already exposed to INFLECTRA, and lasts through the end of the 
observation period of the study, which must include at least 28 calendar days following the 
last administration of a drug under study; a report must be submitted to Pfizer Safety (or its 
designated representative) for any of the types of safety events listed in the table above 
occurring during this period. If a patient was administered a drug under study on the last day 
of the observation period, then the reporting period should be extended for 28 calendar days 
following the end of observation.  Most often, the date of informed consent is the same as the 
date of enrollment.  In some situations, there may be a lag between the dates of informed 
consent and enrollment.  In these instances, if a patient provides informed consent but is 
never enrolled in the study (eg, patient changes his/her mind about participation, failed 
screening criteria, the reporting period ends on the date of the decision to not enroll the 
patient. 
If the investigator becomes aware of a SAE occurring at any time after completion of the 
study and s/he considers the SAE to be related to INFLECTRA, the SAE also must be 
reported to Pfizer Safety.
Causality Assessment
The investigator is required to assess and record the causal relationship.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of
each adverse event.  For AEs with a causal relationship to INFLECTRA, follow-up by the 
investigator is required until the event and/or its sequelae resolve or stabilize at a level 
acceptable to the investigator, and Pfizer concurs with that assessment.
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that INFLECTRA caused or contributed to an adverse event.  If the 
investigator’s final determination of causality is “unknown” and s/he cannot determine 
whether INFLECTRA caused the event, the safety event must be reported within 24 hours. 
If the investigator cannot determine the etiology of the event but s/he determines that 
INFLECTRA did not cause the event, this should be clearly documented on the case report 
form and the NIS AEM Report Form.

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DEFINITIONS OF SAFETY EVENTS
Adverse Events
An AE is any untoward medical occurrence in a patient administered a medicinal product.  
The event need not necessarily have a causal relationship with the product treatment or 
usage.  Examples of adverse events include but are not limited to:  

Abnormal test findings (see below for circumstances in which an abnormal test 
finding constitutes an adverse event);

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Lack of efficacy; 

Drug abuse; 

Drug dependency.
Additionally, for medicinal products, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse;

Off-label use; 

Drug interactions;

Extravasation;

Exposure during pregnancy;

Exposure during breast feeding;

Medication error;

Occupational exposure.

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Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows: 

Test result is associated with accompanying symptoms; and/or,

Test result requires additional diagnostic testing or medical/surgical intervention;
and/or,

Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy; and/or,

Test result is considered to be an adverse event by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event.
Serious Adverse Events
A serious adverse event is any untoward medical occurrence in a patient administered a 
medicinal or nutritional product (including pediatric formulas) at any dose that:

Results in death;

Is life-threatening;

Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute adverse events);

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
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 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above, 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.

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Additionally, any suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious.  The event may be suspected from 
clinical symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited cases 
by PV personnel.  Such cases are also considered for reporting as product defects, if 
appropriate.
Hospitalization
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission.  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).  An emergency room visit does not necessarily constitute a hospitalization; 
however, an event leading to an emergency room visit should be assessed for medical 
importance. 
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable.  
For example, the following reports of hospitalization without a medical AE are not to be 
reported. 

Social admission (eg, patient has no place to sleep);

Administrative admission (eg, for yearly exam);

Optional admission not associated with a precipitating medical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Admission for treatment of a pre-existing condition not associated with the 
development of a new AE or with a worsening of the pre-existing condition (eg, for 
work-up of persistent pre-treatment lab abnormality);

Protocol-specified admission during clinical study (eg, for a procedure required by 
the study protocol).
Scenarios Necessitating Reporting to Pfizer Safety within 24 hours
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication 
error, overdose, misuse, extravasation, lack of efficacy, and occupational exposure are 
described below.

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Exposure During Pregnancy
An exposure during pregnancy (EDP) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed to (eg, environmental) INFLECTRA, or the female becomes, or is found to 
be, pregnant after discontinuing and/or being exposed to INFLECTRA (maternal 
exposure).
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).
2. A male has been exposed, either due to treatment or environmental exposure to 
INFLECTRA prior to or around the time of conception and/or is exposed during the
partner pregnancy (paternal exposure).
As a general rule, prospective and retrospective exposure during pregnancy reports from any 
source are reportable irrespective of the presence of an associated AE and the procedures for 
SAE reporting should be followed.
If a study participant or study participant’s partner becomes, or is found to be, pregnant 
during the study participant’s treatment with INFLECTRA, this information must be 
submitted to Pfizer, irrespective of whether an adverse event has occurred using the NIS 
AEM Report Form and the EDP Supplemental Form. 
In addition, the information regarding environmental exposure to INFLECTRA in a pregnant 
woman (eg, a subject reports that she is pregnant and has been exposed to a cytotoxic product 
by inhalation or spillage) must be submitted using the NIS AEM Report Form and the EDP 
supplemental form.  This must be done irrespective of whether an AE has occurred. 
Information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy; in addition, 
follow-up is conducted to obtain information on EDP outcome for all EDP reports with 
pregnancy outcome unknown.  A pregnancy is followed until completion or until pregnancy 
termination (eg, induced abortion) and Pfizer is notified of the outcome.  This information is 
provided as a follow up to the initial EDP report.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).

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If the outcome of the pregnancy meets the criteria for an SAE (eg, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
procedures for reporting SAEs should be followed.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to investigational product.
Additional information regarding the exposure during pregnancy may be requested.  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 study participant will be provided with the Pregnant 
Partner Release of Information Form to deliver to his partner. It must be documented that the 
study participant was given this letter to provide to his partner.
Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated AE.  An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an AE associated with such a 
drug’s administration, the AE is reported together with the exposure during breastfeeding.
Medication Error
A medication error is any unintentional error in the prescribing, dispensing or administration 
of a medicinal product that may cause or lead to inappropriate medication use or patient harm 
while 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:

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);

Confusion with regard to invented name (eg, trade name, brand name).

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The investigator must submit the following medication errors to Pfizer, irrespective of the 
presence of an associated AE/SAE:

Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE.

Medication errors that do not involve a patient directly (eg, potential medication 
errors or near misses).  When a medication error does not involve patient exposure to 
the product the following minimum criteria constitute a medication error report:

An identifiable reporter;

A suspect product;

The event medication error.
Overdose, Misuse, Extravasation
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product are 
reported to Pfizer by the investigator, irrespective of the presence of an associated AE/SAE.
Lack of Efficacy
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE or the indication for use of the Pfizer 
product.
Occupational Exposure
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the 
investigator, irrespective of the presence of an associated AE/SAE.
10.1. Single Reference Safety Document
The FDA Approved product label will serve as the single reference safety document during 
the course of the study, which will be used by Pfizer safety to assess any safety events 
reported to Pfizer Safety by the investigator during the course of this study.  The SRSD 
should be used by the investigator for prescribing purposes and guidance.
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
A final report and executive summary slide deck will be provided to Pfizer upon the 
completion of the study; no interim reports are currently planned.  In addition, congressional 
abstracts and manuscripts will be considered as appropriate with respect to study results and 
included countries.

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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 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. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this NI study protocol that the investigator becomes aware of.

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12. REFERENCES
1.
European Medicines Agency recommends approval of first two monoclonal-antibody 
biosimilars [press release]. 2013.
2.
Ben-Horin S, Vande Casteele N, Schreiber S, Lakatos PL. Biosimilars in Inflammatory 
Bowel Disease: Facts and Fears of Extrapolation. Clinical gastroenterology and 
hepatology : the official clinical practice journal of the American Gastroenterological 
Association. Dec 2016;14(12):1685-1696.
3.
Farkas K, Rutka M, Balint A, et al. Efficacy of the new infliximab biosimilar CT-P13 
induction therapy in Crohn's disease and ulcerative colitis - experiences from a single 
center. Expert opinion on biological therapy. 2015;15(9):1257-1262.
4.
Gecse KB, Lovasz BD, Farkas K, et al. Efficacy and Safety of the Biosimilar Infliximab 
CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, 
Nationwide Cohort. Journal of Crohn's & colitis. Feb 2016;10(2):133-140.
5.
Jung YS, Park DI, Kim YH, et al. Efficacy and safety of CT-P13, a biosimilar of 
infliximab, in patients with inflammatory bowel disease: A retrospective multicenter 
study. Journal of gastroenterology and hepatology. Dec 2015;30(12):1705-1712.
6.
Kang YS, Moon HH, Lee SE, Lim YJ, Kang HW. Clinical Experience of the Use of 
CT-P13, a Biosimilar to Infliximab in Patients with Inflammatory Bowel Disease: A 
Case Series. Digestive diseases and sciences. Apr 2015;60(4):951-956.
7.
Nikiphorou E, Kautiainen H, Hannonen P, et al. Clinical effectiveness of CT-P13 
(Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with 
established rheumatic disease. Report of clinical experience based on prospective 
observational data. Expert opinion on biological therapy. 2015;15(12):1677-1683.
8.
Smits LJ, Derikx LA, de Jong DJ, et al. Clinical Outcomes Following a Switch from 
Remicade(R) to the Biosimilar CT-P13 in Inflammatory Bowel Disease Patients: A 
Prospective Observational Cohort Study. Journal of Crohn's & colitis. Nov 
2016;10(11):1287-1293.
9.
Tanaka Y, Yamanaka H, Takeuchi T, et al. Safety and efficacy of CT-P13 in Japanese 
patients with rheumatoid arthritis in an extension phase or after switching from 
infliximab. Modern rheumatology. Sep 1 2016:1-10.
10.
FDA approves Inflectra, a biosimilar to Remicade [press release]. 2016.
11.
FDA. Treatment of moderately to severely active Crohn's disease for the reduction of 
the signs and symptoms in patients who have an inadequate response to conventional 
therapies; and treatment of patients with fistulizing Crohn's disease for the reduction in 
the number of draining enterocutaneous fistula(s). FDA; 1998.

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12.
FDA. Reduction in signs and symptoms of rheumatoid arthritis in patients who have 
had an inadequate response to methotrexate. 1999.
13.
Pharmaceuticals J. Full prescribing information for REMICADE. Jansen 
Pharmaceuticals; 2015.
14.
Jorgensen KK, Olsen IC, Goll GL, et al. Switching from originator infliximab to 
biosimilar CT-P13 compared with maintained treatment with originator infliximab 
(NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet 
(London, England). Jun 10 2017;389(10086):2304-2316.
15.
Jahnsen J, Detlie TE, Vatn S, Ricanek P. Biosimilar infliximab (CT-P13) in the 
treatment of inflammatory bowel disease: A Norwegian observational study. Expert 
review of gastroenterology & hepatology. 2015;9 Suppl 1:45-52.
16.
Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance 
therapy for ulcerative colitis. The New England journal of medicine. Dec 08 
2005;353(23):2462-2476.
17.
Vermeire S, Schreiber S, Sandborn WJ, Dubois C, Rutgeerts P. Correlation between the 
Crohn's disease activity and Harvey-Bradshaw indices in assessing Crohn's disease 
severity. Clinical gastroenterology and hepatology : the official clinical practice journal 
of the American Gastroenterological Association. Apr 2010;8(4):357-363.

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13. LIST OF TABLES 
Table 1.
List of Abbreviations ..................................................................................5
Table 2.
Planned Schedule of Events......................................................................19
Table 3.
Patient Baseline Characteristics................................................................19
Table 4.
Clinical and Disease Characteristics.........................................................20
Table 5.
Treatment-Related Adverse Events ..........................................................20
Table 6.
Disease-Related Resource Use .................................................................21
Table 7.
Clinical Outcomes ....................................................................................21
Table 8.
Treatment Details......................................................................................22
Table 9.
Physician Information...............................................................................22
Table 10.
Sample Size for Different Precision Levels (Assuming 95% 
Confidence Level) ....................................................................................23
Table 11.
Clinical Response Outcome Endpoints ....................................................26
Table 12.
Patient Reported Outcome Endpoints.......................................................26
Table 13.
Safety Related Outcome Endpoints..........................................................26
Table 14.
Treatment Pattern Outcome Endpoints.....................................................27
Table 15.
Patient Characteristics Endpoints .............................................................27
Table 16.
Patient Satisfaction and Resource Utilization Outcome Endpoints..........28
14. LIST OF FIGURES
Figure 1.
Study Design.............................................................................................15
Figure 2.
Distribution of Eligible Patients ...............................................................17

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ANNEX 1. LIST OF STAND ALONE DOCUMENTS
14.1. Partial Mayo Questionnaire*
Stool pattern†
Patient reports a normal number of daily stools +0
1-2 more stools than normal +1
3-4 more stools than normal +2
5 or more stools than usual +3
Most severe rectal bleeding of the 
day‡
none +0
Blood streaks seen in the stool less than half the 
time +1
Blood in most stools +2
Pure blood passed +3
Physician’s Global Assessment (to 
be completed by Physician) §
Normal +0
Mild disease +1
Moderate disease +2
Severe disease +3
*The partial Mayo score ranges from 0 to 9, with higher scores indicating more severe disease.
†Each patient serves as his or her own control to establish the degree of abnormality of the stool frequency.
‡ The daily bleeding score presents the most severe bleeding of the day.
§ The physicians global assessment acknowledges the two other criteria, the patient’s daily recollection of 
abdominal discomfort and general sense of wellbeing and other observations such as physical findings and 
the patients performance status.

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14.2. Harvey-Bradshaw Index for Patients with Crohn’s Disease
Category 
Choices 
Score 
General well-being
very well 
0
slightly below par 
1
poor 
2
very poor 
3
terrible 
4
Abdominal pain
none 
0
mild 
1
moderate 
2
severe 
3
Number of liquid stools per day
Abdominal mass
none 
0
dubious 
1
definite 
2
definite and tender 
3
Complications
none 
0
arthralgia
1
uveitis
1
erythema nodosum
1
aphthous ulcers 
1
pyoderma gangrenosum 
1
anal fissure 
1
new fistula 
1
abscess 
1

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14.3. Quality of Life Assessment Using Visual Analog Scale (VAS)
Please mark your overall well-being today (with an ‘X’) using the following ruler from 0 to 
100. 0 indicates worst health (dying) and 100 indicates perfect health.

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14.4. Short Inflammatory Bowel Disease Questionnaire
This questionnaire is designed to find out how you have been feeling during the last 2 weeks.  
You will be asked about symptoms you have been having as a result of your inflammatory 
bowel disease, the way you have been feeling in general, and how your mood has been. 
Please circle the number of your choice below each question.
1. How often has the feeling of fatigue or being tired and worn out been a problem for you 
during the past 2 weeks?
1. All of the time.
2. Most of the time.
3. A good bit of the time.
4. Some of the time.
5. A little of the time.
6. Hardly any of the time.
7. None of the time.
2. How often during the last 2 weeks have you delayed or canceled a social engagement 
because of your bowel problem?
8. All of the time.
9. Most of the time.
10. A good bit of the time.
11. Some of the time.
12. A little of the time.
13. Hardly any of the time.
14. None of the time.
3. As a result of your bowel problems, how much difficulty did you experience doing 
leisure or sports activities you would like to have done during the past 2 weeks?
1. A great deal of difficulty; activities made impossible.
2. A lot of difficulty.
3. A fair bit of difficulty.
4. Some difficulty.
5. A little difficulty.
6. Hardly any difficulty.
7. No difficulty; the bowel problem did not limit sports or leisure activities.

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4. How often during the past 2 weeks have you been troubled by pain in the abdomen?
1. All of the time.
2. Most of the time.
3. A good bit of the time.
4. Some of the time.
5. A little of the time.
6. Hardly any of the time.
7. None of the time.
5. How often during the past 2 weeks have you felt depressed or discouraged?
1. All of the time.
2. Most of the time.
3. A good bit of the time.
4. Some of the time.
5. A little of the time.
6. Hardly any of the time.
7. None of the time.
6. Overall, in the past 2 weeks, how much of a problem have you had with passing large 
amounts of gas?
1. A major problem.
2. A big problem.
3. A significant problem.
4. Some problem.
5. A little trouble.
6. Hardly any trouble.
7. No trouble.
7. Overall, in the past 2 weeks, how much of a problem have you had maintaining or getting 
to the weight you would like to be?
1. A major problem.
2. A big problem.
3. A significant problem.
4. Some problem.
5. A little trouble.
6. Hardly any trouble.
7. No trouble.

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8. How often during the past 2 weeks have you felt relaxed and free of tension?
1. All of the time.
2. Most of the time.
3. A good bit of the time.
4. Some of the time.
5. A little of the time.
6. Hardly any of the time.
7. None of the time.
9. How much of the time during the past 2 weeks have you been troubled by a feeling of 
having to go to the bathroom even though your bowels were empty?
1. All of the time.
2. Most of the time.
3. A good bit of the time.
4. Some of the time.
5. A little of the time.
6. Hardly any of the time.
7. None of the time.
10. How often during the past 2 weeks have you felt angry as a result of your bowel 
problem?
1. All of the time.
2. Most of the time.
3. A good bit of the time.
4. Some of the time.
5. A little of the time.
6. Hardly any of the time.
7. None of the time.

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14.5. Work Productivity and Activity Impairment Assessment
Work Productivity and Activity Impairment Questionnaire:
Specific Health Problem V2.0 (WPAI:SHP)
The following questions ask about the effect of your PROBLEM on your ability to work and 
perform regular activities.  Please fill in the blanks or circle a number, as indicated.
1.
Are you currently employed (working for pay)? 
_____ NO ___ YES
If NO, check “NO” and skip to question 6.
The next questions are about the past seven days, not including today.
2. During the past seven days, how many hours did you miss from work because of
problems associated with your PROBLEM?  Include hours you missed on sick days, 
times you went in late, left early, etc., because of your PROBLEM.  Do not include time 
you missed to participate in this study.
_____ HOURS
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off to participate in this study?
_____HOURS
4. During the past seven days, how many hours did you actually work?
_____HOURS (If “0”, skip to question 6.)

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5. During the past seven days, how much did your PROBLEM affect your productivity 
while you were working?  
Think about days you were limited in the amount or kind of work you could do, days you 
accomplished less than you would like, or days you could not do your work as carefully 
as usual.  If PROBLEM affected your work only a little, choose a low number.  Choose a 
high number if PROBLEM affected your work a great deal. 
Consider only how much PROBLEM affected 
productivity while you were working.
PROBLEM had 
no effect on my 
work
PROBLEM 
completely 
prevented me from 
working
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
6. During the past seven days, how much did your PROBLEM affect your ability to do your 
regular daily activities, other than work at a job? 
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were limited 
in the amount or kind of activities you could do and times you accomplished less than you 
would like.  If PROBLEM affected your activities only a little, choose a low number.  
Choose a high number if PROBLEM affected your activities a great deal. 
Consider only how much PROBLEM affected your ability 
to do your regular daily activities, other than work at a job.
PROBLEM had 
no effect on my 
daily activities
PROBLEM 
completely 
prevented me from 
doing my daily 
activities
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
WPAI:SHP V2.0 (US English)

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14.6. Treatment Satisfaction Questionnaire
TSQM (Version II)
Instructions: Please take some time to think about your level of satisfaction or dissatisfaction 
with the medication you are taking in this clinical trial. We are interested in your evaluation 
of the effectiveness, side effects, and convenience of the medication over the last two to three 
weeks, or since you last used it. For each question, please place a single check mark next to 
the response that most closely corresponds to your own experiences.
1. How satisfied or dissatisfied are you with the ability of the medication to prevent or treat 
the condition? 
□1   Extremely Dissatisfied
□2   Very Dissatisfied
□3   Dissatisfied
□4   Somewhat Satisfied
□5   Satisfied
□6   Very Satisfied
□7   Extremely Satisfied
2. How satisfied or dissatisfied are you with the way the medication relieves symptoms? 
□1   Extremely Dissatisfied
□2   Very Dissatisfied
□3   Dissatisfied
□4   Somewhat Satisfied
□5   Satisfied
□6   Very Satisfied
□7   Extremely Satisfied

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3. As a result of taking this medication, do you experience any side effects at all?
□1   Yes
□0   No
4. How dissatisfied are you by side effects that interfere with your physical health and 
ability to function (eg, strength, energy levels)?
□1   Extremely Dissatisfied
□2   Very Dissatisfied
□3   Somewhat Dissatisfied
□4   Slightly Dissatisfied
□5   Not at all Dissatisfied
□(5) Not Applicable
5. How dissatisfied are you by side effects that interfere with your mental function (eg, 
ability to think clearly, stay awake)?
□1   Extremely Dissatisfied
□2   Very Dissatisfied
□3   Somewhat Dissatisfied
□4   Slightly Dissatisfied
□5   Not at all Dissatisfied
□(5) Not Applicable

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6. How dissatisfied are you by side effects that interfere with your mood or emotions (eg, 
anxiety/fear, sadness, irritation/anger)?
□1   Extremely Dissatisfied
□2   Very Dissatisfied
□3   Somewhat Dissatisfied
□4   Slightly Dissatisfied
□5   Not at all Dissatisfied
□(5) Not Applicable
7. How satisfied or dissatisfied are you with how easy the medication is to use?
□1   Extremely Dissatisfied
□2   Very Dissatisfied
□3   Dissatisfied
□4   Somewhat Satisfied
□5   Satisfied
□6 Very Satisfied
□7   Extremely Satisfied
8. How satisfied or dissatisfied are you with how easy it is to plan when you will use the 
medication each time?
□1   Extremely Dissatisfied
□2 Very Dissatisfied
□3   Dissatisfied
□4   Somewhat Satisfied
□5   Satisfied
□6   Very Satisfied
□7   Extremely Satisfied