Korea Post-marketing Surveillance for Xeljanz (Registered) in Ulcerative Colitis Patients
Conditions: Ulcerative Colitis
Sponsor: Pfizer

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Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 2 of 36 
TABLE OF CONTENTS 
TABLE OF CONTENTS ......................................................................................................... 2 
1. LIST OF ABBREVIATIONS ................................................................................................4 
2. RESPONSIBLE PARTIES ....................................................................................................5 
3. AMENDMENTS AND UPDATES .......................................................................................6 
4. MILESTONES .....................................................................................................................10 
5. RATIONALE AND BACKGROUND ................................................................................11 
6. RESEARCH QUESTION AND OBJECTIVES .................................................................11 
7. RESEARCH METHODS ....................................................................................................11 
7.1. Study design ............................................................................................................11 
7.2. Setting ......................................................................................................................12 
7.2.1. Inclusion criteria .........................................................................................12 
7.2.2. Exclusion criteria ........................................................................................13 
7.2.3. Duration of the study ..................................................................................13 
7.2.4. Dosage and administration .........................................................................13 
7.2.5. Study procedures ........................................................................................15 
7.3. Variables ..................................................................................................................18 
7.3.1. Safety variables ...........................................................................................18 
7.3.2. Effectiveness variables ...............................................................................21 
7.3.3. Effectiveness evaluation .............................................................................21 
7.4. Data sources ............................................................................................................22 
7.4.1. Case report forms ........................................................................................22 
7.4.2. Record retention ..........................................................................................23 
7.5. Study size ................................................................................................................23 
7.6. Data management ....................................................................................................23 
7.7. Data analysis ...........................................................................................................24 
7.7.1. Safety analysis ............................................................................................24 
7.7.2. Effectiveness analysis .................................................................................25 
7.7.3. Quality control ......................................................................................................25 
7.8. Limitations of the research methods .......................................................................26 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 3 of 36 
7.9. Other aspects ...........................................................................................................26 
8. PROTECTION OF HUMAN SUBJECTS ..........................................................................26 
8.1. Patient information and consent ..............................................................................26 
8.2. Patient withdrawal ...................................................................................................27 
8.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..............27 
8.4. Ethical conduct of the study ....................................................................................27 
9. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................27 
9.1. Requirements ...........................................................................................................27 
9.2. Reporting period ......................................................................................................28 
9.3. Causality assessment ...............................................................................................29 
9.4. Definition of safety events ......................................................................................29 
9.4.1. Adverse events ............................................................................................29 
9.4.2. Serious adverse events ................................................................................31 
9.4.3. Scenarios necessitating reporting to Pfizer Safety within 24 hours ...........32 
9.5. Single reference safety document............................................................................35 
10. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........35 
11. REFERENCES ..................................................................................................................35 
12. LIST OF TABLES .............................................................................................................36 
13. LIST OF FIGURES ...........................................................................................................36 
NONE ......................................................................................................................................36 
ANNEX 1. LIST OF STAND ALONE DOCUMENTS .........................................................36 
ANNEX 2. ADDITIONAL INFORMATION .........................................................................36 
 
 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 4 of 36 
1. LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
ADR 
adverse drug reaction 
AE 
adverse event 
AEM 
adverse event monitoring  
ANC 
absolute neutrophil count 
CRF 
case report form 
CRP 
C-reactive protein 
CYP 
cytochrome P450 
EDP 
exposure during pregnancy 
ESR 
erythrocyte sedimentation rate 
GEP 
Good Epidemiological Practice 
GPP 
Good Pharmacoepidemiology Practice 
HDL 
high density lipoprotein 
IEA 
International Epidemiological Association 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ISPE 
International Society for Pharmacoepidemiology 
LDL 
low density lipoprotein 
MFDS 
Ministry of Food and Drug Safety 
NIS 
non-interventional study  
PhRMA 
Pharmaceutical Research and Manufacturers Association 
PMS 
post-marketing surveillance 
pANCA 
perinulclear anti-neutrophil cytoplasmic antibodies 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SRSD 
single reference safety document 
TC 
total cholesterol 
UC 
ulcerative colitis 
VAS 
visual analogue scale 
MedDRA 
Medical Dictionary for Regulatory Activities 
 

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Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 6 of 36 
3. AMENDMENTS AND UPDATES 
 
Amendment 
number 
Date 
Protocol section(s) 
changed 
Summary of 
amendment(s) 
Reasons 
Amendment 1 
23 Jul 
2019 
2. Responsible 
parties 
Change of responsible 
parties 
NISL change 
5. Rationale and 
background 
Least number of 
patients to be 
followed until the end 
of 52weeks mentioned 
Amendment 
recommended by the 
MFDS 
7.1. Study design 
Included how to 
clinically assess the 
efficacy  
Added the content of 
the follow-up for 
long-term users. 
7.2.5. Study 
Procedures  
7.2.5.1. Basic 
Information 
Added the content of 
the follow-up for 
long-term users  
7.2.5.2. 
Demography and 
baseline 
characteristics 
Included Partial Mayo 
Score 
7.3.1. Safety 
variables 
7.3.2. Efficacy 
variables 
7.3.3. Efficacy 
evaluation 
Added the content of 
the follow-up for 
long-term users  
 
7.7.2. Efficacy 
analysis 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 7 of 36 
Amendment 2 
26 Aug 
2019 
7.3.1.1. Adverse 
event 
Added the ‘not 
applicable’ in the 
Causality assessment  
Amendment 
recommended by the 
MFDS 
7.7.1. Safety 
analysis 
Added the definition 
of patients enterting 
this study for the 
safety analysis 
Described the special 
popluations in detail 
7.7.2 Efficacy 
analysis 
Added the definition 
of the patients 
enterting this study for 
the efficacy analysis 
Added the efficacy 
anlaysis for 
incompleted long-
term users 
7.7.4. Statistical 
consideration 
Described the 
statistical analysis in 
detail 
Amendment 3 
19 Sep 
2019 
7.3.2. Efficacy 
variables 
7.3.3. Efficacy 
evaluation 
Added the final 
efficacy variable in 
efficacy variables 
Added the final 
efficacy variable by 
investigator 
Amendment 4 
15 Oct 
2019 
7.1. Study design 
Removed the 
Truelove and Witts’s 
Score 
Mayo score is more 
frequently used in 
actual medical 
practice 
7.3.1.1. Adverse 
events 
7.6. Data 
management 
Changed the criteria 
of AE terminology 
from the WHO-ART 
to MedDRA 
Changed for 
digitalization and  
standardization of 
AE terminology  
7.3.2. Efficacy 
variables 
7.3.3. Efficacy 
evaluation 
Clarified the final 
efficacy evaluation 
To reflect the actual 
medical practice 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 8 of 36 
Amendment 5 
06 Feb 
2020 
4.Milestones 
Add RMP report 
submission timeline 
Amended according 
to the MFDS 
comments 
 
7.7.1.Safety 
analysis 
Add analysis and 
evaluation methods 
for safety 
specification 
according to RMP 
Amendment 6 
23 Mar 
2021 
5. Rationale and 
background 
Modify number of 
patients in the study 
Add retrospective 
data collection 
method 
Change of research 
methods 
7.1 Study design 
7.2.1. Inclusion 
criteria 
7.2.5. Study 
procedures 
7.2.5.1. Basic 
information 
7.2.5.2. 
Demography and 
baseline 
characteristics 
Amendment 7 
25 Mar 
2022 
Total 
Change ‘Efficacy’ 
to ‘Effectiveness’ if 
it is evaluated under 
usual clinical 
practice 
To clarify the 
definition of terms 
5. Rationale and 
background 
Remove 
retrospective data 
collection method 
Change of research 
methods 
7.1 Study design 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 9 of 36 
7.2.1. Inclusion 
criteria 
7.2.5. Study 
procedures 
7.2.5.1. Basic 
information 
7.2.5.2. 
Demography and 
baseline 
characteristics 
7.3.1.2. 
Laboratory test 
Remove laboratory 
normal ranges of the 
center 
Change of data 
collection methods 
7.4.2. Record 
retention 
Add record retention 
period 
To align with 
regulation 
7.5. Study Size 
Modify number of 
patients in the study 
Change of research 
methods 
 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 10 of 36 
4. MILESTONES 
Milestone 
Planned date 
Start of data collection  
27 May 2019 
End of data collection  
19 September 2022 
First year (1-1) periodic report (MFDS) 
19 May 2019 
First year (1-2) periodic report (MFDS) 
19 November 2019 
Second year (2-1) periodic report (MFDS) 
19 May 2020 
Second year (2-2) periodic report (MFDS) 
19 November 2020 
Third year annual report (MFDS) 
19 November 2021 
Final study report (MFDS) 
19 December 2022 
- Abbreviations: MFDS=Ministry of Food and Drug Safety. 
- RMP periodic report will be submitted every year after RMP approval, and final report will be submitted after December 
2022 considering completion schedule of xeljanz post-marketing surveillance final report in patients with ulcerative colitis. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 12 of 36 
 
Table 1. Mayo Score for ulcerative colitis4 
 
Xeljanz will be administered according to the “Dosage and Administration” of the approved 
labeling.  There is no visit or activity mandated by this study.  The investigator will collect 
patient data and record the information on each patient’s case report form (CRF). 
Each investigator will sequentially enroll all patients to whom Xeljanz is prescribed for the 
first time according to the local product label, and who agree to participate in this study by 
signing the data privacy statement. Safety is the primary endpoint of this study, which will be 
assessed based on adverse events (AEs) that have occured between the first dose of Xeljanz to 
the next visit.  
As a secondary endpoint, the investigator will performe the final effectiveness evaluation based 
on the clinical impression plus the Mayo score or Partial Mayo score. The Mayo score or the 
Partial Mayo Score at week 8, 16 and 24(also 52 for the long-term users) is assessed to see the 
remission, clinical response or mucosal healing. To assess the effectiveness of the Xeljanz. 
Mayo score is based on a total score of 12 points by evaluating and calculating the four clinical 
evaluation criteria: Stool frequency, Rectal bleeding, Findings of endoscopy, and Physician's 
global assessment. (Table 1) Partial Mayo Score is calculated by the sum of the remaining 
evaluations, except for the findings of endoscopy score.  
7.2. Setting 
7.2.1. Inclusion criteria 
To be included in the study all patients will have received at least 1 dose of Xeljanz for the 
treatment of the following indication as per local labelling:  
 
Moderately to severely active ulcerative colitis (UC) who have had an inadequate response 
or intolerance to the basic treatments or biological agents 

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CCI

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 16 of 36 
to be collected will be allocated to each study site by Pfizer at the time of execution of a 
contract with each site.  
• Completion of the study: If the patient completed 24 weeks of treatment (52 weeks for the 
long-term users), check “yes”. Otherwise, check “no” and choose reason for the 
discontinuation: AE; lack of effectiveness; others. 
• Date of CRF completion: Record the date of CRF completion.  
• Signature of investigator: Contracted investigator must sign after identifying the CRF.  
• Confirmation of data privacy statement: If the patient has signed the data privacy statement 
to indicate agreement for using his/her personal and medical information, check the box of 
“yes” on the CRF.  If not, check “no” and exclude the case from the study.  
7.2.5.2. Demography and baseline characteristics 
The following will be recorded on the CRF for each patient: 
• Age: Record actual age of the patient at the time of enrollment.  The age should be 
calculated by the date of birth.  
• Sex: Check the box next to “male” or “female” on the CRF. 
• Height: Record by unit of cm.  
• Weight: Record by unit of kg.  
• Herpes zoster vaccination: Record if the patient had received vaccine of herpes zoster: 
yes; no; unknown. 
• Smoking: Record smoking status of the patient: ex-smoking; current smoking; 
non-smoking; unknown. 
• Duration of the disease: Record the duration of disease since the date that the patient was 
initially diagnosed with UC.  
• Severity of disease activity: Assess the severity (Mild, Moderate, Severe) by  measuring 
Mayo or partial Mayo score and calcuating the total score of 12 or 9 points based on 
clinical evaluation criteria: Stool frequency, rectoral bleeding, findings of endoscopy, and 
physician's global assessment. Partial Mayo score excludes the findings of endoscopy. 
The severity for partial Mayo score is defined as 0-1 for remission, 2-4 for mild, 5-6 for 
moderate and 7-9 for severe disease activity. 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 17 of 36 
• Previous UC treatments: Only record UC treatments received 6 months prior to the 
initiation of Xeljanz.  Record name of the medication/therapy, route and duration of the 
administration, and overall response, if possible. 
• Latent tuberculosis: Record if the patient has latent tuberculosis: yes; no; unknown. 
• Renal impairment: Record if the patient has renal disorder: yes (severe/moderate/mild); 
none.  
• Hepatic impairment: Record if the patient has hepatic disorder: yes 
(severe/moderate/mild); none.  
• Other past/present diseases: Record “yes” or “no” for medical history.  If “yes”, record 
adequate full name of the past or present disease according to the Medical Terminology 
Dictionary written by the Korean Medical Society.  Past or present disease will be 
determined based on the date of the first dose of Xeljanz. 
7.2.5.3. Administrative status for medicinal product 
The following will be recorded on the CRF for each patient: 
• Treatment duration: Record start date and stop date (year/month/day) of the treatment of 
Xeljanz.  If the medication is being continued at the completion of the study, record the 
start date only.  
• Daily dose: Record single dose of Xeljanz in mg.    
• Daily dosing frequency: Record dosing frequency per day. 
• Reason for dose adjustment: If there are any dose adjustments during the study, record 
the reason(s).  
7.2.5.4. Concomitant treatments 
Any concomitant treatments should be recorded on the CRF for each patient.  The 
information should include: 
• Name of the drug: Record generic name of the concomitant medication. 
• Daily dose: Record single dose and dosing frequency of the concomitant medication. 
• Duration of the treatment: Record the start date and stop date (year/month/day) of the 
concomitant medication.  If the medication is being continued at the completion of the 
study, record the start date only and check “ongoing”. 
• Purpose of the treatment: Record purpose of the concomitant treatment in detail. 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 18 of 36 
7.2.5.5. Safety and effectiveness data 
Please refer to Section 7.3 for safety and effectiveness assessment and data collection.  
 
7.3. Variables 
7.3.1. Safety variables 
Safety will be assessed by the investigator based on all AEs that occur during the 24 weeks 
(52 weeks for the long-term users) from the first treatment for all patients who have received 
at least 1 dose of Xeljanz according to the local product document. 
7.3.1.1. Adverse events  
Please refer to Section 9 for the definition of non-serious and serious adverse events (SAEs).   
Any AEs observed and reported within the reporting period will be recorded on the CRF by 
the investigator, regardless of the causal relationship with Xeljanz (see Section 9.2).  The 
AEs can be reported by the patients.  The investigator will also collect AE data by asking the 
patient questions such as “Have you had any health problem since the last visit?” 
Check either “yes” or “no” in the AE section of CRF.  If “yes”, record the following 
information: 
Event name: Record the name of the AE according to the MedDRA(Medical Dictionary for 
Regulatory Activities). If there is no appropriate term in the MedDRA, record the name of 
the AE according to the Medical Terminology Dictionary written by the Korean Medical 
Society.  If possible, specify diagnosis, not individual symptoms.  
Date of onset: Record the onset date of the AE.  Record approximate date if an actual date is 
unknown. 
Date of recovery: Record the stop date of the AE if the outcome of the AE is recovered or 
recovered with sequelae (see below).  Record approximate date if an actual date is unknown. 
Seriousness: Check either “yes” or “no” to indicate if the event is a SAE.  If “yes’ record 
appropriate category of the seriousness (see Section 9for the definition and reporting of 
SAEs).  
Severity: Evaluation of AE severity must be done according to the following categories: 
• Mild: Not causing any significant problem to the patient.  Administration of medicinal 
product continues without dose adjustment.  
• Moderate: Causes a problem that does not interfere significantly with usual activities or 
the clinical status.  Dose of the medicinal product is adjusted or other therapy is added 
due to the AE. 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 19 of 36 
• Severe: Causes a problem that interferes significantly with usual activities or the clinical 
status.  The medicinal product is stopped due to the AE. 
If the severity of an AE changes, the AE must be entered separately.  Record the stop date of 
the previous severity and onset date of the new severity – along with completion of all other 
related items. 
Causality assessment: The causal relationship of AEs to the medicinal product must be 
allocated by the investigator according to the following criteria in alignment with the 
requirements of MFDS: 
• Certain 
o It follows a reasonable time sequence from administration of the drug (before and 
after the study medication); 
o It could not be explained by other drugs, chemical substances or accompanying 
diseases; 
o It has clinically reasonable reaction on cessation of the drug; 
o It has pharmacological or phenomenological reaction to re-administration of the 
drug, where necessary. 
• Probable/likely 
o It follows a reasonable time sequence from administration of the drug (before and 
after the study medication); 
o It could not be explained by other drugs, chemical substances or accompanying 
diseases; 
o It has clinically reasonable reaction on cessation of the drug (no information on 
re-administration).  
• Possible 
o It follows a reasonable time sequence from administration of the drug;  
o It could also be explained by other drugs, chemical substances or accompanying 
diseases; 
o It lacks information or has unclear information on discontinuation of the drug. 
• Unlikely 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 20 of 36 
o It is not likely to have a reasonable causal relationship from administration of the 
drug.  Rather, it seems to be temporary; 
o It could also be reasonably explained by other drugs, chemical substances or latent 
diseases. 
• Conditional/unclassified 
o It needs more data to make an appropriate assessment or its additional data are being 
reviewed. 
• Unassessible/unclassifiable 
o Lack of sufficient information or conflicting information hampers accurate causality 
assessment or supplementation or confirmation. 
• Not applicable 
o Causality is assessed but does not fall into any categories 
All AEs, except for those with a causality of “unlikely”, are considered as AEs whose causal 
relationship to the study drug can not be excluded (ie, adverse drug reaction [ADR]).  
Action taken: With regard to the medicinal product, actions will include:  
• Permanently discontinued; 
• Temporarily discontinued or delayed; 
• Dose reduced; 
• Dose increased; 
• No change; 
• Not applicable.  
Outcome: Evaluation of outcome will include:  
• Recovered;  
• Recovered with sequelae; 
• Recovering; 
• Not recovered;  

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 21 of 36 
• Unknown. 
Please refer to Section 9 for the requirements for reporting safety events to Pfizer Safety 
during the study. 
7.3.1.2. Laboratory test  
Recommended laboratory tests and time points are included in Table 4.  Test results of chest 
X-ray, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), other blood chemistry, 
hematology, and tuberculin test should be recorded, if conducted.   
Table 4 Recommended Laboratory Test 
 
Lymphocyte 
Neutrophils 
Hemoglobin 
Lipids (TC, HDL, LDL) 
Baseline 
X 
X 
X 
X 
4 to 8weeks after treatment 
 
X 
X 
X 
Every 3 months 
X 
X 
X 
 
Abbreviations: TC=total cholesterol, HDL= high density lipoprotein, LDL=low density lipoprotein. 
In case there are any clinically significant laboratory abnormalities (as per the investigator’s 
judgment) that occur after the treatment of Xeljanz compared to baseline, the tests should be 
recorded in detail on the CRF, including test results before and after Xeljanz treatment, a 
causal relationship to Xeljanz, and any comments from the investigator. 
Please refer to Section 9.4.1 for the criteria for determining whether an abnormal objective 
test finding should be reported as an AE.  
7.3.2. Effectiveness variables 
The Mayo score or the Partial Mayo score at week 8, 16, 24 and also 52 for the long-term 
users is assessed is assessed to see the remission, clinical response or mucosal healing. 
Investigator will perform the final effectiveness evaluation of the drug into 4 categories 
based on the clinical impression plus Mayo score or Partial Mayo score (‘Improved’, 
‘Unchanged’, ‘Aggravated’, ‘Not assessible’). 
7.3.3. Effectiveness evaluation 
Effectiveness assessment will be performed by the accredited investigator in the Korean 
health care center.  The investigator will perform the final effectiveness evaluation at 
baseline and after 8, 16 and 24 weeks of treatment based on the clinical impression and any 
of the commonly used effectiveness assessment criteria such as Mayo score or Partial Mayo 
score, and record the assessment results in each patient’s CRF. 52nd week will be added for 
the long-term users. If the patient does not complete the 24 or 52 weeks of treatment, relevant 
data should be collected based on the last assessment performed at the time of treatment 
discontinuation. The final evaluation of the effectiveness will be determined by the 
investigator  into 4 categories(‘Improved’, ‘Unchanged’, ‘Aggravated’, ‘Not assessible’). 

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 22 of 36 
 
Improved 
(Symptoms of ulcerative colitis have improved or showed adequate 
maintenance effect after taking Xeljanz) 
 
Unchanged 
(Symptoms have not changed much since taking Xeljanz) 
 
Aggravated (Symptoms have worsened after taking Xeljanz) 
 
Not assessible ( Reason :  
                   ) 
If the overal effectiveness assessment is evaluated as ‘Improved’, ‘Unchanged’ or 
‘Aggrevated’, it is analyzed to be clinically significant. If the overall effectiveness assessment 
is evaluated as ‘Not assessible’, it is analyzed as not clinically significant. Among the 4 
categories, ‘Improved’ is considered that the drug is effective. ‘Unchanged’ and ‘Aggravate’ 
are considered that there is a lack of effectiveness.   
The Mayo score or the Partial Mayo score, which is referred in the effectiveness evaluation, 
are commonly used in actual medical practice. The Mayo score or the Partial Mayo Score at 8, 
16 and 24 weeks(also 52 for the long-term users) will be assessed after the administration of 
Xeljanz, and Mayo Score measures the number of stool frequency, rectal bleeding, findings of 
endoscopy, and physician’s global assessment. In total, based on the total score of 12 points, 
0-2 points is rated as Remission, 3-5 as Mild, 6-10 as Moderate, and 11-12 as Severe. Partial 
Mayo Score is calculated by the sum of the remaining evaluations, except for the findings of 
endoscopy score. Based on the total score of 9 points, 0-1 is rated as Remission, 2-4 as Mild, 
5-6 as Moderate and 7-9 as Severe.  
Remission is defined as Mayo score being less than or equal to 2 (in case of partial Mayo 
score, the score is less than or equal to 1) and other subscores not greater than 1 and rectal 
bleeding score of 0. Clinical response is defined as a decrease of Mayo score of more than 3 
points and 30% from the baseline and a decrease of 1 or more in rectal bleeding score or 
rectal bleeding score of 0 or 1. Clinical response per partial Mayo score is a decrease of 
partial Mayo score of 2 or more and 30 % from the baseline and a decrease of 1 or more in 
rectal bleeding score or rectal bleeding score of 0 or 1. Clinical remission is defined as Mayo 
score being less than or equal to 2 and other subscores not bigger than 1. Endoscopic 
remission is endoscopic subscore of 0 and mucosal healing is defined as an endoscopic score 
of 0 or 1. 
 
 
7.4. Data sources  
7.4.1. Case report forms 
The investigator will review source documents and complete an electronic CRF for each 
included patient.  The completed original CRFs are the sole property of Pfizer and should not 
be made available in any form to the third parties, except for authorized representatives of 
Pfizer or appropriate regulatory authorities, without written permission from Pfizer. 

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CCI

Xeljanz® (Tofacitinib Citrate) 
A3921343 NON-INTERVENTIONAL STUDY PROTOCOL 
Amendment 7, 25 Mar 2022 
 
 
PFIZER CONFIDENTIAL  
 
Page 24 of 36 
7.7. Data analysis  
Analysis will be performed for the pooled data collected by each investigator during the 
re-examination period.  Total number of centers participating, total number of cases enrolled 
and retrieved, and total number of cases included in the analysis will be presented in summary 
tables.  Evaluation of data will primarily consist of summary displays (eg, descriptive statistics, 
tables, and graphs).   
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 Pfizer.  The SAP may modify the plans outlined in the protocol; any major modifications 
of primary endpoint definitions or their analyses will be reflected in a protocol amendment. 
7.7.1. Safety analysis 
The primary interest of this study is the incidence of AEs investigated during the 
re-examination period.  Incidence of each AE will be presented with 95% confidence 
interval.  Serious, related, and/or unexpected AEs will be summarized separately. 
Safety analysis will be performed for all patients registered for this study who are prescribed 
at least 1 dose of Xeljanz according to the local label and followed up for safety data. 
To identify the factors that affect safety, subgroup analysis for various factors will be 
performed, including the classification of AEs by body system, and comparison of incidence 
of AEs by sex, age, presence of concurrent diseases, presence of concomitant medications, 
baseline disease activity, etc. 
In case the drug was administered to special populations such as elderly people over 65, or 
patients with renal or hepatic disorders during the study, subgroup analysis will also be 
performed for each of those populations. The safety and effectiveness of Xeljanz in pediatric 
patients have not been established. 
Unexpected AEs/ADRs will be classified by medical review with reference to the local 
product document.  Events already included in the “Precautions for use” section of the local 
product document will be classified as “expected”.  All other events that are not included in 
the “Precautions for use” section of the local product document will be classified as 
“unexpected”.  An unexpected AE includes any events that may be symptomatically and 
patho-physiologically related to an event listed in the labeling, but differs from the labeled 
event because of greater severity or specificity.  
In the case of an adverse event with important potential risks and important identified risks in 
relation to the safety specification under the risk management plan, or if missing information 
patient group is recruited, actions according to the label will be taken, and the safety 
information is presented separately. 

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conducted 
according 
to 
Pfizer’s 
procedures 
and 
the 
guidelines 
for 
Good 
Pharmacoepidemiology Practices (GPP) (see Section 8.4). 
7.7.4 Statistical consideration 
For the safety and effectiveness outcome variables, the statistically significant differences for 
each classification group are statistically processed using the χ2 test (p≤0.05). The incidence 
of each anomaly is presented with a 95% confidence interval. In order to analyze the factors 
affecting safety, a list of abnormal case expressions was prepared by the types of abnormal 
cases and by the background factors of the subjects (by gender, age  and the presence or 
absence of accompanying diseases). Analyze the factors using a categorical data analysis 
method (Chi-square test, Fisher's Exact test). For statistically significant items, the 
pharmacological significances are described, and major adverse events, drug adverse reactions, 
and unexpected adverse events will be summarized in a table. 
 
7.8. Limitations of the research methods 
This is a non-interventional PMS study conducted in the Republic of Korea to satisfy the 
requirements of MFDS:  The protocol is determined by regulation of MFDS and not the 
specific disease and drug characteristics.  The observational, non-controlled, and 
non-randomized design of this study has intrinsic limitations. 
7.9. Other aspects 
Not applicable. 
 
8. PROTECTION OF HUMAN SUBJECTS 
8.1. 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 data privacy statement (in place of an informed consent form) must be in compliance 
with local regulatory requirements and legal requirements. 
The data privacy statement used in this study, and any changes made during the course of the 
study, must be prospectively approved by both Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) and Pfizer before use. 
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 

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risks associated with participation.  The investigator, or a person designated by the 
investigator, will obtain the written data privacy statement from each patient or the patient’s 
legally acceptable representative before any study-specific activity is performed.  The 
investigator will retain the original of each patient’s signed data privacy statement. 
8.2. 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 Pfizer for safety, behavioral, or 
administrative reasons.  In any circumstance, every effort should be made to document the 
patient outcome, if possible.  The investigator should inquire about the reason for withdrawal 
and follow-up with the patient regarding any unresolved AEs. 
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. 
8.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
The study protocol will be submitted to MFDS prior to the study.  The ethical consideration 
on this study will be evaluated by the IRB/ IEC in each clinical site prior to the study, if the 
site has an approval process for this PMS study according to the local standard operation 
procedure of the site.  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, and other relevant documents, 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.  
8.4. 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 GPP issued by the International Society for 
Pharmacoepidemiology (ISPE), Pharmaceutical Research and Manufacturers Association 
(PhRMA) guidelines, and Korea PMS regulations and/or guidelines.  
 
9. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS  
9.1. Requirements 
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the non-interventional study (NIS) adverse event monitoring 
(AEM) Report Form to Pfizer Safety.  These requirements are delineated for three types of 
events: (1) SAEs; (2) non-serious AEs (as applicable); and (3) scenarios involving drug 

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exposure, including exposure during pregnancy, exposure during breast feeding, medication 
error, overdose, misuse, extravasation, and occupational exposure.  These events are defined 
in Section 9.4.   
Safety event 
Recorded on the CRF  
Reported on the NIS AEM 
Report Form to Pfizer Safety 
within 24 hours of awareness 
SAE 
All 
All 
Non-serious AE 
All 
None 
Scenarios involving exposure to a 
drug under study, including exposure 
during pregnancy, exposure during 
breast feeding, medication error, 
overdose, misuse, extravasation; lack 
of efficacy; and occupational 
exposure 
All (regardless of whether 
associated with an AE), except 
occupational exposure  
All (regardless of whether 
associated with an AE) 
 
For each AE, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a SAE 
(see section "Serious Adverse Events” below)  
Safety events listed in the table above must be reported to Pfizer within 24 hours of 
awareness of the event by the investigator regardless of whether the event is determined 
by the investigator to be related to a drug under study.  In particular, if the SAE is fatal or 
life-threatening, notification to Pfizer must be made immediately, irrespective of the extent of 
available event information.  This timeframe also applies to additional new (follow-up) 
information on previously forwarded safety event reports.  In the rare situation that the 
investigator does not become immediately aware of the occurrence of a safety event, the 
investigator must report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the events. 
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 CRF.  In general, this will include a description of the AE 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.  
9.2. Reporting period  
For each patient, the safety event reporting period begins at the time of the patient’s first dose 
of Xeljanz or the time of the patient’s data privacy statement if s/he is already exposed to 

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Xeljanz, 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 Xeljanz; 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 data privacy statement is the same as the date of enrollment.  In some 
situations, there may be a lag between the dates of data privacy statement and enrollment.  In 
these instances, if a patient provides data privacy statement but is never enrolled in the study 
(eg, patient changes his/her mind about participation), 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 Xeljanz, the SAE must also be reported to 
Pfizer Safety.   
9.3. 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 AE.  For AEs with a causal relationship to Xeljanz, 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 Xeljanz caused or contributed to an AE.  If the investigator’s final 
determination of causality is “unknown” and s/he cannot determine whether Xeljanz 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 Xeljanz 
did not cause the event, this should be clearly documented on the CRF and the NIS AEM 
Report Form.  
9.4. Definition of safety events  
9.4.1. 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 AEs include but are not limited to:   
• Abnormal test findings (see below for circumstances in which an abnormal test 
finding constitutes an AE); 
• Clinically significant symptoms and signs; 
• Changes in physical examination findings; 

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• 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. 
Abnormal test findings 
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE 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 AE by the investigator or sponsor. 

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Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
9.4.2. Serious adverse events 
A SAE 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 AEs); 
• 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. 
In this study, the onset of disease includes but is not limited to the following, which should 
be considered as medically important SAEs of special interest: serious infection, 
tuberculosis, cancer, or lymphocyte proliferative disorders.  These events will be monitored, 
analyzed, and reported.   
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 pharmacovigilance personnel.  Such cases are also considered for reporting as product 
defects, if appropriate. 
Hospitalization 

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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). 
9.4.3. 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. 
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) Xeljanz or the female becomes, or is found to be, 
pregnant after discontinuing and/or being exposed to Xeljanz (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). 

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2. A male has been exposed, either due to treatment or environmental exposure to 
Xeljanz 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 Xeljanz, this information must be submitted to 
Pfizer, irrespective of whether an AE has occurred using the NIS AEM Report Form and the 
EDP Supplemental Form.  
In addition, the information regarding environmental exposure to Xeljanz in a pregnant 
woman (eg, a patient 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). 
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 includes:  
• 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 the investigational product 

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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). 
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; 

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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. 
9.5. Single reference safety document 
The local product document will serve as the SRSD 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. 
10. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
For the first 2 years, 6-month reports will be submitted to MFDS (ie, reports 1-1, 1-2, 2-1, and 
2-2,).  Thereafter, data collected in the 3rd and finally 4th year will be reported to MFDS 
annually.  The final study report (ie, re-examination report) will be submitted to MFDS in the 
4th year to include all data collected during the whole study period (see Section 4).  
11. REFERENCES 
1. MFDS. Basic standards for the re-examination of new medicines. Notification No. 
2013-185.  
2. MFDS. Guidelines for re-examination of new medicines. July 2012.  
3. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. 
Br Med J 1955;2:1041–8. 
4. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for 
mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 
1987;317:1625–9. 
 

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12. LIST OF TABLES  
Table 1. 
Mayo score for Ulcerative Colitis 
Table 2. 
Recommended Dosage for Ulcerative Colitis Patients 
Table 3. 
Recommended Laboratory Test 
 
 
13. LIST OF FIGURES 
None 
ANNEX 1. LIST OF STAND ALONE DOCUMENTS 
None 
ANNEX 2. ADDITIONAL INFORMATION 
Not applicable