Retrospective Non-interventional Multicenter Patient Chart Data Study on Tofacitinib Realworld Experience in Ulcerative Colitis in Finland (FinTofUC)
Conditions: Ulcerative Colitis
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
Retrospective non-interventional multicenter 
patient chart data study on tofacitinib real-
world experience in ulcerative colitis in 
Finland (FinTofUC)
Protocol number
A3921390
Protocol version identifier
Version 1
Date
01 July 2021
Active substance
ATC L04AA29
Medicinal product
Tofacitinib (Xeljanz) 
Research question and objectives
To identify key characteristics of patients 
treated with tofacitinib for ulcerative colitis 
and describe the real-world effectiveness of 
tofacitinib for the treatment of ulcerative 
colitis in Finland.
Author
 
, NI study lead, Pfizer Finland
This document contains confidential information belonging to Pfizer. Except as otherwise agreed to in writing, 
by accepting or reviewing this document, you agree to hold this information in confidence and not copy or 
disclose it to others (except where required by applicable law) or use it for unauthorized purposes. In the event 
of any actual or suspected breach of this obligation, Pfizer must be promptly notified.
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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................2
2. LIST OF ABBREVIATIONS................................................................................................4
3. RESPONSIBLE PARTIES....................................................................................................6
4. AMENDMENTS AND UPDATES.......................................................................................6
5. MILESTONES.......................................................................................................................7
6. RATIONALE AND BACKGROUND..................................................................................7
7. RESEARCH QUESTION AND OBJECTIVES ...................................................................8
7.1. Definitions.................................................................................................................8
7.2. Primary Objective .....................................................................................................9
7.2.1. To Characterize the UC Patient Group Treated with Tofacitinib.................9
7.3. Secondary objectives.................................................................................................9
7.3.1. To Assess the Real-world Effectiveness of Tofacitinib. ..............................9
7.3.2. To Assess Treatment Lines Prior to Tofacitinib Treatment. ......................11
8. RESEARCH METHODS ....................................................................................................12
8.1. Study Design ...........................................................................................................12
8.2. Setting......................................................................................................................13
8.2.1. Inclusion Criteria ........................................................................................14
8.2.2. Exclusion Criteria.......................................................................................14
8.3. Variables..................................................................................................................14
8.4. Data Sources............................................................................................................18
8.5. Study Size................................................................................................................18
8.6. Data Management ...................................................................................................18
8.7. Data Analysis ..........................................................................................................19
8.8. Quality Control........................................................................................................19
8.9. Limitations of the Research Methods......................................................................20
8.10. Other Aspects ........................................................................................................20
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................20
9.1. Patient Information..................................................................................................20
9.2. Patient Consent........................................................................................................20
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9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..............20
9.4. Ethical conduct of the study....................................................................................20
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................21
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........21
12. REFERENCES ..................................................................................................................22
13. LIST OF TABLES.............................................................................................................23
14. LIST OF FIGURES ...........................................................................................................23
ANNEX 1. LIST OF STAND ALONE DOCUMENTS .........................................................23
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .........................................23
ANNEX 3. ADDITIONAL INFORMATION.........................................................................23
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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
5-ASA
5-aminosalicylic acid
AE
adverse event
ATC
anatomic therapeutic chemical classification system
B-hb
blood hemoglobin
B-leuk
blood leukocytes
B-ly
blood lymphocytes
B-neutr
blood neutrophiles
B-thromb
blood thrombocytes
BMI
body mass index
CRO
clinical research organization
eDMT
electronic data mining tool
EHR
electronic health record 
EIM
extraintestinal manifestations
ERVA
erityisvastuualue
f-calpro
fecal calprotectin
FPFV
first patient first visit
GPP
good pharmacoepidemiology practices
HUS
Helsinki University Hospital
IBD
inflammatory bowel disease 
ICD-10
International Statistical Classification of Diseases 
and Related Health Problems 10th revision
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Abbreviation
Definition
ICMJE
International Committee of Medical Journal Editors
IEC
Independent Ethics Committee
IRB
Institutional Review Board
IPAA
ileal pouch-anal anastomosis
JAK
Janus kinase 
LPLV
last patient last visit
NI
non-interventional
P-CRP
plasma C-reactive protein
P-alb
plasma albumin
pMayo
partial Mayo
QC
quality control
QoL
quality of life
RCT
randomized controlled trial
RWE
real-world evidence 
SAP
statistical analysis plan 
STAT
signal transducers and activators of transcription
TyK2
tyrosine kinase 2
UC
ulcerative colitis 
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3. RESPONSIBLE PARTIES
Principal Investigator(s) of the Protocol
Name, degree(s)
Job Title
Affiliation
Address
 
, MD
 
 
 
 
 MD
 
 
, MD
 
, PhD
, 
PhD
 
4. AMENDMENTS AND UPDATES
None.
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5. MILESTONES
Milestone
Planned date
Start of data collection 
01 December 2021
End of data collection 
30 May 2022
Final study report
01 May 2023
6. RATIONALE AND BACKGROUND
Inflammatory bowel diseases (IBD) is an umbrella term used to describe disorders that 
involve chronic inflammation of the digestive tract. IBD includes ulcerative colitis (UC) and 
Crohn’s disease. More than 50,000 Finns suffer from IBD1 with approximately 2,000 new 
cases diagnosed each year.2 UC is a chronic, relapsing systemic disease that mainly affects 
the gastrointestinal tract, resulting in acute and chronic intestinal inflammation. It is 
characterized by inflammation in the large bowel (colon). Typical symptoms include blood in 
stool, diarrhea, urgency, and fatigue, and often the disease has substantial consequences for 
work participation and sick leave. The annual incidence of UC in Finland is about 25 new 
cases per 100,000 inhabitants. The prevalence is estimated at 550/100,000 inhabitants.3
Based on data from the Social Insurance Institution of Finland, the incidence of UC in 
Finland between 2000–2007 is 2.5–3 times higher than that of Crohn's disease.4 The steady 
increase in the incidence of UC in Finland from the beginning of the 21st century to 2007 
was demonstrated in a registry study of Social Insurance Institution of Finland compensation 
conducted by Jussila et al.5
Tofacitinib is an oral Janus kinase (JAK) inhibitor indicated for the treatment of several 
immune-mediated diseases including UC. JAKs are intracellular enzymes that transmit 
signals arising from cytokine or growth factor-receptor interactions on the cellular membrane 
to influence cellular processes of hematopoiesis and immune cell function. Within the 
signaling pathway, JAKs phosphorylate and activate signal transducers and activators of 
transcription (STATs) which modulate intracellular activity including gene expression. 
Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the 
phosphorylation and activation of STATs. JAK enzymes transmit cytokine signaling through 
pairing of JAKs (eg, JAK1/JAK3, JAK1/JAK2, JAK1/tyrosine kinase 2 (TyK2), 
JAK2/JAK2).6 Tofacitinib inhibited the in vitro activities in particular of JAK1/JAK3.7
However, the relevance of specific JAK combinations to therapeutic effectiveness is largely 
unknown. The efficacy and safety of tofacitinib has been demonstrated as induction and 
maintenance therapy in 3 Phase 3, randomized, placebo-controlled trials in patients with 
moderate to severe UC.8-10 However, the study design and procedures in the randomized 
controlled trial (RCT) may not always reflect clinical practice and treatment patterns. Thus, it 
is of interest to clinicians, patients, and taxpayers to describe outcomes in the environment 
where the drug will be used. 
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Real world evidence (RWE) has become increasingly important in providing additional 
evidence of treatment effectiveness in clinical practice. RWE data for tofacitinib has been 
published for rheumatoid arthritis and an overview of these data has recently been 
provided11 while currently the primary sources of data for tofacitinib in UC patients is from 
the clinical development program including induction, maintenance, and long term extension 
studies in controlled patient populations.10
The use of observational data will allow for the generation of data on the induction, 
maintenance, and effectiveness of tofacitinib outside the confines of the RCT. Examples of 
additional data that can be collected using the non-interventional, registry data collection 
includes fecal calprotectin levels - a predictor of clinical and endoscopic outcomes, 
extraintestinal manifestations - conditions often observed in patients with IBD and dose 
changes outside of the construct of the clinical trial setting.
The aim of UC treatment is to achieve remission, improve quality of life (QoL) and avoid 
complications from the disease including surgeries and hospital admissions as well as side-
effects from long-term corticosteroid use. Despite existing treatment with mesalazine, 
immunomodulators and biologics, severe disease and complications are common in UC. 
Hence, additional treatments including those with different new modes/mechanisms of 
actions are needed.
7. RESEARCH QUESTION AND OBJECTIVES
The objective of this study is to describe and evaluate real-world data of tofacitinib for the 
treatment of UC in Finland in terms of clinical outcomes, treatment lines, and to identify the 
key characteristics of the patients treated with tofacitinib. 
7.1. Definitions
Active disease: 

An endoscopic Mayo sub-score12 of ≥2 or fecal-calprotectin (f-calpro) >250mg/kg.
Clinical response:

A full Mayo score12 decrease of ≥3 points and a decrease of ≥30% from baseline, 
with a decrease of ≥1 point on the rectal bleeding sub score or an absolute rectal 
bleeding score of ≤1. 

A partial Mayo score (ie, Mayo score without endoscopic assessment) decrease of 
≥2 points and reduction of at least 25% in partial Mayo (pMayo) score from baseline 
with an accompanying decrease in rectal bleeding sub score of ≥1 point or absolute 
rectal bleeding sub score of ≤1.
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Clinical remission:

A full Mayo score of ≤2 points with no individual sub score exceeding 1 point, with 
rectal bleeding sub-score of 0.

A pMayo score <2 points with rectal bleeding sub-score of 0.
7.2. Primary Objective
7.2.1. To Characterize the UC Patient Group Treated with Tofacitinib.
a.
Patient demographics at tofacitinib treatment initiation: age, gender, weight, height,
smoking status, body mass index (BMI), treating hospital. 
b. Disease characteristics: age at diagnosis, duration of disease, and extent of colonic 
involvement according to the Montreal classification: E1 (ulcerative proctitis), 
E2 (left sided, distal colitis), E3 (pancolitis).
c.
Disease severity as assessed by Mayo score and f-calpro at the initiation of tofacitinib 
use.
d. Laboratory results for biochemical inflammatory markers plasma C-reactive protein 
(P-CRP), blood thrombocytes (B-thromb), plasma albumin (P-alb), blood leukocytes 
(B-leuk), blood lymphocytes (B-ly), blood neutrophiles (B-neutr), blood hemoglobin
(B-hb) and f-calpro at the start of tofacitinib treatment (baseline data). 
e.
Endoscopic findings including histology at the start of tofacitinib treatment (baseline 
data). 
7.3. Secondary objectives
7.3.1. To Assess the Real-world Effectiveness of Tofacitinib.
a.
Proportion of patients who are taking tofacitinib at week 8, 16, 24 and 52.
b. To assess rates of clinical remission defined by a full or partial Mayo score at week 8, 
16, 24 and 52.
c.
To assess rates of clinical response defined by a full or partial Mayo score at week 8, 
16, 24 and 52.
d. Proportion of patients in steroid-free clinical remission at weeks 8, 16, 24, and 52 as 
defined by full or partial Mayo who did not require any corticosteroid treatment 
during the period ≥4 weeks prior to the visit (for all patients and for those treated with 
corticosteroids at baseline).
e.
Proportion of patients reaching clinical response as defined by full or partial Mayo 
score at week 8, 16, 24 and 52.
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f.
Time to response as assessed by a decrease as defined by full or partial Mayo score. 
g. Proportion of responders defined by a f-calpro reduction of ≥50%, ≥75% or ≥90% at 
week 8, 16, 24 and 52 compared to baseline.
h. Proportion of patients reaching f-calpro below 250 mg/kg at week 8, 16, 24 and 52 of 
those that had f-calprotectin above 250 mg/kg at baseline and change from baseline in 
f-calpro at week 8, 16, 24 and 52. 
i.
Proportion of patients in sustained remission (pMayo and full Mayo score) from week 
8 to week 16, 24 and 52.
j.
Proportion of patients in sustained remission (pMayo and full Mayo score) from week 
16 to week 24 and 52.
k. Proportion of patients in sustained steroid free remission (pMayo and full Mayo
score) at week 16 to 24 and 52 (for all patients and for those treated with 
corticosteroids at baseline).
l.
Change in partial and full Mayo score at weeks 8/16/24/52.
m. Proportion of patients in sustained endoscopic remission (sub score = 0), mucosal 
healing (sub score 0-1) or endoscopic response (sub score reduction from baseline of 
≥1) from week 8 to week 16, 24 and 52.
n. Proportion of patients in physician assessed histological remission determined as 
inactive disease, or normal histology, and change from baseline in histology 
assessment (0= normal histology, 1= inactive disease and 2 = active disease) at week 
8/16/24/52.
o. Proportion of patients in sustained steroid free remission (pMayo and full Mayo 
score) (for all patients and for those treated with corticosteroids at baseline) and 
endoscopic remission (sub score = 0), mucosal healing (sub score 0-1) or endoscopic 
response (sub score reduction from baseline of ≥1) from week 8 to week 16, 24 and 
52.
p. Comparison of response and remission (pMayo and full Mayo score) based on the 
extent of colonic involvement.
q. Proportion of patients with corticosteroid tapering at weeks 8/16/24/52 and their 
tapering rates and doses. 
r.
Proportion of patients with improvement in stool frequency sub score of 1 or more 
points and change from baseline in stool frequency sub score at week 8, 16, 24 and 
52.
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s.
Proportion of patients with improvement in rectal bleeding sub score of 1 or more 
points and change from baseline in rectal bleeding sub score at week 8, 16, 24 and 52. 
t.
Proportion of patients reaching normal P-CRP levels (below 4mg/L) and change from 
baseline in P-CRP levels at week 8/16/24/52.
u. Proportion of patients reaching normal B-hb levels (men: 134–167 g/L, women: 117–
155 g/L) and change from baseline in B-hb levels at week 8/16/24/52.
v. Proportion of patients reaching normal B-leuk levels (3.4-8.2 x 109/L) and change 
from baseline in B-leuk levels at week 8/16/24/52.
w. Proportion of patients reaching normal B-Thromb (150–360 x 109/L) and change 
from baseline in B-Thromb levels at week 8/16/24/52.
x. Proportion of patients reaching normal B-ly (1.3-3.6 x 109/L) and change from 
baseline in B-ly levels at week 8/16/24/52.
y. Proportion of patients reaching normal B-neutr (1.5-6.7 x 109/L) and change from 
baseline in B-neutr levels at week 8/16/24/52.
z. Proportion of patients reaching normal P-alb (18-39 years: 36-48 g/L, 40-69 years: 
36-45 g/L, 70 years and over: 34-45 g/L) and change from baseline in P-alb levels at 
week 8/16/24/52.
aa. Proportion of patients with extended tofacitinib induction dose (additional 8 weeks 
with 10mg). 
bb. Real-world dosing of tofacitinib, eg, usage of a higher dose (10 mg) as maintenance 
therapy. 
cc. Survival without drug discontinuation, colectomy or UC-related hospitalization 
(using time to event analysis).
7.3.2. To Assess Treatment Lines Prior to Tofacitinib Treatment.
a.
Number and type of previous UC treatments. 
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8. RESEARCH METHODS 
8.1. Study Design
This is a retrospective non-interventional multicenter patient chart data study collecting real 
world data of tofacitinib treated patients with UC from 21 Finnish hospital district and 
Helsinki city hospital (included in “hospital districts” hence forward for the purpose of this 
protocol) databases and for whom data is available. Real-world data through health care 
registers is an excellent means to understand the tofacitinib treatment and use landscape in 
Finland.
The main purpose is to characterize the patient population receiving tofacitinib, their 
demographics and clinical characteristics. Patient characteristics before and after the use of 
tofacitinib will be determined for all patients. If possible, depending on patient numbers from 
different areas, regional differences will also be analyzed. 
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Figure 1.
Schematic View of Study Flow
8.2. Setting
The target population for this study is adult ulcerative colitis patients who were prescribed 
tofacitinib. Estimated number of patients in this study is 100-150, with the aim of covering 
all ulcerative colitis patients in Finland treated with tofacitinib. The main inclusion criteria 
are a diagnosis of ulcerative colitis (ICD-10: K51) between January 2010 and December 
2021 and treatment with tofacitinib. The main exclusion criteria are age under 18 years, use 
of tofacitinib before national reimbursement decision on 01 March 2019 and history of 
panproctocolectomy, ileal pouch-anal anastomosis (IPAA) or ileostomy. 
The data collected has been generated as part of standard clinical care, treatment, and follow-
up of ulcerative colitis patients. In accordance with the Finnish Act on Secondary Use of 
Health and Social Data 552/2019 (in Finnish: Laki sosiaali- ja terveystietojen toissijaisesta 
käytöstä), health registry data can be processed in scientific studies without patient consent. 
The purpose of this act is to establish conditions for the effective and secure processing of, 
and access to, personal health and social data for certain secondary purposes, such as 
research and statistics, innovation and development, knowledge management, teaching and 
authority planning. Thus, the Secondary Act creates a clear legal basis for the use of such 
registered data for research and innovation related to, for example, the health and well-being 
of citizens, the prevention of disease and the development of new treatment methods. This 
relatively new legislation is also a welcome unification of the fragmented Finnish national 
rules regarding the use of healthcare and social welfare data. In addition, it takes into 
consideration current data protection requirements. 
The data will be collected by data miners in all hospital districts across Finland and entered 
into an electronic data mining tool (eDMT) which will be designed for the study in 
collaboration with Finnish clinicians. The data will be used to investigate and describe the 
patient population, treatment strategies and disease development.
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Figure 2.
Study Timeline
FPFV= First patient first visit, LPLV= Last patient last visit.
Please note that dates are subject to change depending on how long permit process with 
Findata takes.
8.2.1. Inclusion Criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study:
1. Xeljanz (tofacitinib) usage for ulcerative colitis.
2. Diagnosis of ulcerative colitis (ICD-10: K51.0, K51.1, K51.2, K51.3, K51.5, K51.8, 
K51.9) between January 2010 and December 2021 (incident or prevalent). 
8.2.2. Exclusion Criteria
Patients meeting any of the following criteria will not be included in the study:
1. Age <18 years at the start of tofacitinib use.
2. Use of tofacitinib before reimbursement (01 Mar 2019).
3. < 8 weeks of treatment with tofacitinib at the start of data mining.
4. History of panproctocolectomy, IPAA or ileostomy. 
8.3. Variables
The primary variable is the first recording (date) with tofacitinib for the treatment of 
ulcerative colitis (ICD-10: K51). Additional variables to be collected according to the list in 
Table 1. 
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Table 1. Variables Collected in This Study
Data source for all variables is the eDMT based on patient charts. 
Variable
Role
Operational definition
Tofacitinib start date
Index
Inclusion criteria 1
Exclusion criteria 2
First day on tofacitinib administration 
Date of birth
Exclusion criteria 1
Primary objective 7.2.1.a
Age will be defined as of index date
History of bowel surgery
Exclusion criteria 4
Panproctocolectomy, IPAA or 
ileostomy
Gender
Primary objective 7.2.1.a
Male/female
Smoking status
Primary objective 7.2.1.a
Current/ex-smoker/non-
smoker/unknown
BMI
Primary objective 7.2.1.a
Derived from weight and height
Weight
Primary objective 7.2.1.a
kg
Height
Primary objective 7.2.1.a
cm
Treating hospital
Primary objective 7.2.1.a
name of treating hospital
Mayo score
Primary objective 7.2.1.c
Secondary objectives 7.3.1.b, 
7.3.1.c, 7.3.1.d, 7.3.1.e, 7.3.1.f, 
7.3.1.i, 7.3.1.j, 7.3.1.k, 7.3.1.l, 
7.3.1.o, 7.3.1.p.
Sum of “endoscopic findings”, “stool
frequency”, Doctors assessment of 
disease severity” and “rectal bleeding”
First UC diagnose
Primary objective 7.2.1.b
Inclusion criteria 2
Date
Extent of colonic 
involvement
Primary objective 7.2.1.b
Montreal classification: E1, E2 or E3
Endoscopic findings
Primary objective 7.2.1.c and 
7.2.1.e.
Secondary objective 7.3.1.m
0-3 (mayo score component)
Histological activity
Primary objective 7.2.1.e
Secondary objective 7.3.1.n
Active disease (2) / inactive disease 
(1) /normal histology (0) / not 
determined
Clinician’s assessment of 
disease severity
Primary objective 7.2.1.c
0-3 (mayo score component)
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Variable
Role
Operational definition
Stool frequency
Primary objective 7.2.1.c
Secondary objectives 7.3.1.r
0-3 (mayo score component)
Rectal bleeding
Primary objective 7.2.1.c
Secondary objective 7.3.1.s
0-3 (mayo score component)
Fecal calprotectin
Primary objective 7.2.1.d,
Secondary objectives 7.3.1.g
and 7.3.1.h.
mg/kg
Plasma CRP
Primary objective 7.2.1.d
Secondary objective 7.3.1.t
mg/L
Blood hemoglobin
Primary objective 7.2.1.d,
Secondary objective 7.3.1.u
g/L
Blood leukocytes
Primary objective 7.2.1.d
Secondary objective 7.3.1.v
cells/L
Blood thrombocytes
Primary objective 7.2.1.d
Secondary objective 7.3.1.w
cells/L
Blood lymphocytes
Primary objective 7.2.1.d
Secondary objective 7.3.1.x
cells/L
Blood neutrophiles
Primary objective 7.2.1.d
Secondary objective 7.3.1.y
cells/L
Plasma albumin
Primary objective 7.2.1.d
Secondary objective 7.3.1.z
g/L
Tofacitinib dose
Secondary objectives 7.3.1.a, 
7.3.1.aa and 7.3.1.bb
mg*times/per day or “not on 
treatment”
Colectomies
Secondary objective 7.3.1.cc
Date
Type of healthcare 
contact
Secondary objective 7.3.1.cc
outpatient visit, remote contact,
emergency visit or 
hospitalization
Prior IBD treatments 

corticosteroids

5-aminosalicylic 
acid (5-ASA)
Secondary objective 7.3.2
Yes/no (For each treatment)
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Variable
Role
Operational definition

azathioprine

6-mercaptopurine

methotrexate

cyclosporine

ustekinumab

vedolizumab

adalimumab

infliximab

golimumab
Concomitant medications

corticosteroids

5-ASA
Secondary objective 7.3.1.q,
product & dose
Extraintestinal 
manifestations: arthralgia, 
arthritis, sacroiliitis, 
pyoderma gangrenosum, 
erythema nodosum, 
primary sclerosing 
cholangitis, uveitis, 
ankylosing spondylitis, 
aphthous stomatitis, 
psoriasis
Yes/no per pre-specified list
Prior diagnoses
Yes/no per pre-specified list
Death date or lost to 
follow up
Used to define end of follow up
Date
Detailed definitions of variables and their analysis is available in the statistical analysis plan
(SAP). 
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8.4. Data Sources
This study relies on a secondary use of existing and available data in patient registers and 
patient charts in Finland. The data will be gathered from hospital patient information
systems. All data in this study is collected from these patient information systems and made 
available in aggregated form for data-analysis. 
8.5. Study Size
This study is an observational study designed to provide mainly descriptive summary 
information. There are no hypotheses in the study. Hence sample size calculations are not 
applicable. The objective is to include all patients that have used tofacitinib in UC in Finland. 
Estimated number of observations is 100-150 subjects to the timing on the data collection.
8.6. Data Management 
This study protocol will be evaluated and approved by the Finnish Health and Social Data 
Permit Authority Findata before any activity starts. Findata will issue permits and deliver the 
data for this study. Based on the protocol the clinical research organization (CRO) 
Medaffcon will design an eDMT form which will be provided to Findata. A predefined list of 
data miners will be submitted to Findata. eDMT form will be provided to data miners by 
Findata. 
Each data miner will have access to a set of patient charts to collect the requested data using 
protected eDMTs. The eDMT is created and maintained by Granitics Oy. In each hospital 
district (register holder) the assigned data miner will transfer completed eDMT forms to 
Findata. Findata will provide the pseudonymized pooled data into a secure analysis 
environment, maintained by the same authority in a csv, xlsx or comparable format (not 
eDMT-format). Only a preassigned biostatistician from Medaffcon has access to this 
multifactor identification protected remote server, and only aggregate-level data can be 
extracted. Thus, individual patients cannot be identified from this data set. 
Medaffcon will analyze the data using the statistical software R (version 3.6.1 or higher). 
Only aggregate results can be extracted from the Findata analysis environment and be 
available for evaluation for sponsor. Data will be stored at Findata. Medaffcon will be the 
study register holder, and analyses will be performed according to the SAP by Medaffcon 
and Pfizer.
Internal validity will be assured by consulting Finnish clinical experts on data integrity, 
clinical relevance, and plausibility of the results.
All results of this study will be presented in aggregate level data only, no individual level 
data can be reported. Any patient groups of less than 5 patients cannot be exported from 
Findata servers. This means that eg, if two patients smoke, it will be reported as “<5 patients 
smoke”. 
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8.7. 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.
All analysis will be performed by Medaffcon. In short, patients will be described at baseline
using appropriate summary statistics. 
All analyses are descriptive of nature, and descriptive statistics and/or illustrations will be 
reported. 
 Persistence of treatment will be assessed using 
time-to-event models (namely Kaplan-Meier fit and/or Cox proportional hazards model). 
Changes in treatment outcomes (vs. baseline) will be assessed using repeated measures 
longitudinal models. Baseline data may be used as covariates in the models where feasible
and appropriate.
All p-values are descriptive in nature, and there are no a priori hypotheses to be tested. 
P-values lower than 0.05 will be considered statistically significant. All statistical tests will 
be considered hypothesis generating, and any significant results should be validated later. 
Statistical interpretation of the results will be validated by Medaffcon statisticians/Data 
Scientists with relevant degree.
8.8. Quality Control
Medaffcon has an internal quality control (QC)/log documentation used for RWE studies. 
The document records general data QC (including for example measures for data and 
variable coverages, number of individuals and data rows, changes as function of time and 
checks for systematic gaps on data coverage and outliers in the data where appropriate). 
Additionally, all notes or data processing and definitions, especially any deviations from 
SAP, will be recorded and later reported. All analyses and data processing will be performed 
using R, a language and environment for statistical computing and graphics, in R-studio 
environment. All analysis scripts will be saved, and there is version control and external 
back-ups for the scripts. At the end of study, all scripts will be archived to assure analysis 
reproducibility, and plausible later audits (by client and/or from scientific publication side).
All study results will be discussed within Medaffcon and Pfizer teams, and any uncertainties 
will be further validated by clinical experts and/or wider team of Pfizer and/or Medaffcon 
RWE experts and Data Scientists where appropriate.
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8.9. Limitations of the Research Methods
The main strength of this study is the nation- and patient-wide coverage of the cohort. The 
study is expected to include all 21 health care districts in Finland. The data is also versatile as 
it is derived from the patient information systems in the hospital districts. 
The main limitation of the study are its’ retrospective nature and the expected number of 
observations (approximately 100 – 150 patients). Therefore, some sub-group or stratified
analyses are not necessarily possible. It is also likely that the data is partially incomplete 
because of the variation between hospitals. All variables or sum variable components are not 
necessarily available from different electronical health records. Tofacitinib has been used in 
Finland for a rather short time so data for all endpoints at all timepoints may not be 
calculated/available. As in the registry studies in general the primary data source (hospital 
electronic health record [EHR]) in this study may be prone to potential human errors. Data is 
subject to gaps and human errors made by physicians entering data into the system.
8.10. Other Aspects
Not applicable.
9. PROTECTION OF HUMAN SUBJECTS
9.1. Patient Information 
This study involves data that exist in anonymized structured format and contain no patient 
personal information.
9.2. 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.
9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
No waiver was received as this is not applicable. Per the Act on Secondary Use of Health and 
Social Data 552/2019 (in Finnish: Laki sosiaali- ja terveystietojen toissijaisesta käytöstä), no 
institutional review board or independent ethics committee for this retrospective registry 
study is required.
9.4. Ethical conduct of the study
Per the Act on Secondary Use of Health and Social Data 552/2019 (in Finnish: Laki sosiaali-
ja terveystietojen toissijaisesta käytöstä), no ethical approval for this retrospective registry
study is required. This study protocol will be evaluated and approved by the Finnish Health 
and Social Data Permit Authority Findata before any activities.
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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).13
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
Secondary Data Collection Study Structured Data Analysis 
This study involves data that exist as structured data by the time of study start or a 
combination of existing structured data and unstructured data, which will be converted to 
structured form during the implementation of the protocol solely by a computer using
automated/algorithmic methods, such as natural language processing.
In these data sources, individual patient data are not retrieved or validated, and it is not 
possible to link (ie, identify a potential association between) a particular product and medical 
event for any individual. Thus, the minimum criteria for reporting an adverse event (AE) 
(ie, identifiable patient, identifiable reporter, a suspect product, and event) cannot be met.
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
The detailed results obtained from this study will be available upon publication. Research 
results from this study will be published in peer reviewed scientific journals and international 
scientific congresses. The Authorship of any publications resulting from this study will be 
determined based on the International Committee of Medical Journal Editors (ICMJE) 
Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in 
Medical Journals.
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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12. REFERENCES
1.
Sipponen T. Tulehduksellisten suolistosairauksien hoito - mitä uutta? Duodecim. 
2018(134(8)):817-825.
2.
Kolho K-L, Färkkilä M. Tulehdukselliset suolistosairaudet - mikä vialla? Duodecim. 
2017(133(18)):1701-1709.
3.
Sipponen T. Haavainen paksusuolitulehdus (colitis ulcerosa). In: Lääkärin Käsikirja. ; 
2020.
4.
Färkkilä M, Isoniemi H, Heikkinen M, et al. Gastroenterologia ja hepatologia. Vol 
2018. Duodecim.
5.
Jussila A, Virta LJ, Kautiainen H, et al. Increasing incidence of inflammatory bowel 
diseases between 2000 and 2007: A nationwide register study in Finland. Inflamm 
Bowel Dis. 2012;18(3):555-561. doi:https://doi.org/10.1002/ibd.21695.
6.
Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol 
Rev. 2009;228(1):273-287. doi:10.1111/j.1600-065X.2008.00754.x.
7.
O’Shea J. Targeting the Jak/STAT pathway for immunosuppression. Ann Rheum Dis. 
2004;63(Suppl 2):ii67-ii71. doi:10.1136/ard.2004.028290.
8.
Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an Oral Janus Kinase Inhibitor, in 
Active Ulcerative Colitis. N Engl J Med. 2012;367(7):616-624. 
doi:10.1056/NEJMoa1112168.
9.
Sandborn WJ, Panés J, D’Haens GR, et al. Safety of Tofacitinib for Treatment of 
Ulcerative Colitis, Based on 4.4 Years of Data From Global Clinical Trials. Clin 
Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2019;17(8):1541-1550. 
doi:10.1016/j.cgh.2018.11.035.
10.
Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as Induction and Maintenance Therapy 
for Ulcerative Colitis. N Engl J Med. 2017;376(18):1723-1736. 
doi:10.1056/NEJMoa1606910.
11.
Caporali R, Zavaglia D. Real-world experience with tofacitinib for the treatment of 
rheumatoid arthritis. Clin Exp Rheumatol. 2019;37(3):485-495.
12.
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated Oral 5-Aminosalicylic Acid Therapy 
for Mildly to Moderately Active Ulcerative Colitis. N Engl J Med. 1987;317(26):1625-
1629. doi:10.1056/NEJM198712243172603.
13.
Guidelines for good pharmacoepidemiology practice (GPP). Pharmacoepidemiol Drug 
Saf. 2016;25(1):2-10. doi:10.1002/pds.3891.
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13. LIST OF TABLES 
Table 1. Variables Collected in This Study.............................................................................15
14. LIST OF FIGURES
Figure 1.
Schematic View of Study Flow................................................................13
Figure 2.
Study Timeline..........................................................................................14
ANNEX 1. LIST OF STAND ALONE DOCUMENTS
None.
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Not required. 
ANNEX 3. ADDITIONAL INFORMATION
Not applicable.
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