A Non-Interventional Multinational Study of Tofacitinib in Patients Treated for Psoriatic Arthritis
Conditions: Psoriatic Arthritis
Sponsor: Pfizer

Tofacitinib (CP-690,550)
A3921332 NON-INTERVENTIONAL STUDY PROTOCOL
Version 2.0, 14 February 2023
PFIZER CONFIDENTIAL
CT24-WI-GL02-RF01 5.0 Non-Interventional Study Protocol Template For Primary Data Collection Study 01-
Jun-2022
Page 1 of 59
NON-INTERVENTIONAL STUDY PROTOCOL
Study Information
Title
A Non-Interventional Multinational Study of Tofacitinib in Patients
Treated for Psoriatic Arthritis
Protocol number
A3921332
Protocol version 
identifier
2.0
Date
14 February 2023
Active substance
L04AA29
tofacitinib citrate
Medicinal product
Tofacitinib (Xeljanz®)
Research question 
and objectives
The aim of this study is to evaluate the effectiveness of treatment 
with tofacitinib on disease activity, remission, and quality of life 
(QoL) in patients with Psoriatic Arthritis (PsA) over a 12-month 
observation period.
Primary Objective
To evaluate the proportion of patients achieving low disease 
activity (LDA) after 6 months of follow-up.
Secondary Objectives
1. To evaluate the proportion of patients achieving LDA after 
3 and 12 months of follow-up.
2. To evaluate the proportion of patients achieving minimum 
disease activity (MDA) after 3, 6, and 12 months of
follow-up.
3. To evaluate the proportion of patients achieving remission
after 3, 6, and 12 months of follow-up.
4. To evaluate change from baseline in Psoriatic Arthritis 
Impact of Disease 12 Questions (PsAID12) score after 3, 6, 
and 12 months of follow-up.
5. To evaluate change from baseline in Spondylarthritis 
Research Consortium of Canada Enthesitis Index
090177e19d31ca1c\Approved\Approved On: 24-May-2023 13:53 (GMT)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 of 5 9
( S P A R C C-EI ) sc ore after 3, 6, a n d 1 2 m o nt hs of f oll o w- u p.
6.
T o i de ntif y  pr o g n ostic i n dicat ors f or ac hie vi n g L D A after 3, 
6, a n d 1 2 m o nt hs of f oll o w - u p.
7.
T o e val uate c ha n ge fr o m baseli ne i n Q o L sc ores after 3, 6, a n d 
1 2 m o nt hs of f oll o w - u p.
E x pl or at or y o bjecti ves
T o e val uate c ha n ges i n meas ures of disease acti vit y ( Ps oriatic
Art hritis Disease
Acti vit y Sc ore [ P A S D A S] a n d Disease Acti vit y i n
Ps oriatic Art hritis [ D A P S A]) fr o m baseli ne after 3, 6, a n d 1 2 m o nt hs 
of f oll o w -u p.
A ut h or
M ai n A ut h or : Pr of.
Tel A vi v Me dical Ce nter,
Israel
C o -A ut h or :
, Pfizer 
Israel
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer.  E xce pt as ot her w ise a gree d t o i n writi n g, b y 
acce pti n g or re vie wi n g t his d oc u me nt, y o u a gree t o h ol d t his i nf or mati o n i n c o nfi de nce a n d n ot c o p y or discl ose it 
t o ot hers (e xce pt w here re q uire d b y a p plica ble la w ) or use it f or u na ut h orize d p ur p oses.  I n t he e ve nt of a n y act ual 
or s us pecte d breac h of t his o bli gati o n, Pfizer m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)
P P D
P P D

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 of 5 9
1. T A B L E O F C O N T E N T S
1. T A B L E O F C O N T E N T S .......................................................................................................3
2. LI S T O F A B B R E VI A TI O N S ................................................................................................5
3. R E S P O N SI B L E P A R TI E S ....................................................................................................9
4. A B S T R A C T .........................................................................................................................1 0
5. A M E N D M E N T S A N D U P D A T E S .....................................................................................1 1
6. MI L E S T O N E S .....................................................................................................................1 3
7. R A TI O N A L E A N D B A C K G R O U N D ................................................................................1 3
8. R E S E A R C H Q U E S TI O N A N D O BJ E C TI V E S .................................................................1 5
8. 1. Researc h Q uesti o n ...................................................................................................1 5
8. 2. O bjecti ves ................................................................................................................1 5
9. R E S E A R C H M E T H O D S................................ ....................................................................1 6
9. 1. St u d y  Desi g n...........................................................................................................1 6
9. 1. 1. E n d p oi nts ....................................................................................................1 7
9. 2. Setti n g ......................................................................................................................1 8
9. 2. 1. I ncl usi o n Criteria................................ ........................................................1 8
9. 2. 2. E xcl usi o n Criteria .......................................................................................1 9
9. 3. Varia bles ..................................................................................................................1 9
9. 3. 1. E nr oll me nt Visit ( Visit 1) ...........................................................................2 0
9. 3. 2. F oll o w -u p Visits 2, 3, 4 (at a p pr o xi matel y M o nt hs 3, 6, a n d 1 2) ...............2 2
9. 3. 3. E n d of St u d y ...............................................................................................2 4
9. 3. 4. Deri ve d Varia bles .......................................................................................2 4
9. 4. Data S o u rces............................................................................................................2 7
9. 4. 1. P h y sical Assess me nts .................................................................................2 7
9. 4. 2. P R Os ...........................................................................................................2 8
9. 4. 3. Pr o g n ostic Fact ors ......................................................................................2 9
9. 5. St u d y  Size................................................................................................................3 0
9. 6. Data Ma na ge me nt ...................................................................................................3 0
9. 6. 1. Case Re p ort F or ms ( C R Fs) .........................................................................3 1
9. 6. 2. Rec or d Rete nti o n ........................................................................................3 1
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 of 5 9
9 . 7. Data A nal ys is ..........................................................................................................3 2
9. 7. 1. A nal y sis P o p ulatio ns ................................ ..................................................3 2
9. 7. 2. Effecti ve ness A nal yses ...............................................................................3 2
9. 7. 3. Safet y A nal ys es ..........................................................................................3 3
9. 7. 4. I nteri m A nalys is..........................................................................................3 3
9. 8. Q ualit y  C o ntr ol........................................................................................................3 3
9. 9. Li mitati o ns of t he Researc h Met h o ds................................ ......................................3 4
9. 1 0. Ot her As pects ........................................................................................................3 4
1 0. P R O T E C TI O N O F H U M A N S U BJ E C T S ........................................................................3 5
1 0. 1. Patie nt I nf or mati o n ................................................................................................3 5
1 0. 2. Patie nt C o nse nt ......................................................................................................3 5
1 0. 3. Patie nt Wit h dra wal................................ ................................................................3 6
1 0. 4. I nstit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee (IE C) ............3 6
1 0. 5. Et hical C o n d uct of t he St u d y ................................................................................3 7
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S ......................................................................................................................3 8
1 2. P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S ........4 6
1 3. R E F E R E N C E S ..................................................................................................................4 7
1 4. LI S T O F T A B L E S .............................................................................................................5 1
1 5. LI S T O F FI G U R E S ...........................................................................................................5 1
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S .........................................................5 1
A N N E X 2. A D DI TI O N A L  I N F O R M A TI O N.........................................................................5 1
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 5 of 5 9
2. LI S T O F A B B R E VI A TI O N S
A b bre vi ati o n
Defi niti o n
A C R 2 0
A merica n C olle ge of R he u mat ol o g y ( Criteria) 2 0 %
A E
a d verse e ve nt
A E M
a d verse e ve nt m o nit ori n g
A L K P H
al kali ne p h os p hatase
A L T
ala ni ne tra nsa mi nase
A S T
as partate tra nsa mi nase
b D M A R D
bi ol o gic Disease - M o dif yi n g A ntir he u matic Dr u g
B S A
B o d y S urface Area
C B C
c o m plete bl o o d c o u nt
CI
c o nfi de nce i nter val
C R F
case re p ort f or m
C R O
c o ntract researc h or ga nizati o n
C R P
C- reacti ve pr otei n
cs D M A R D
c o n ve nti o nal s ynt hetic Disease -M o dif y i n g
A ntir he u matic Dr u g
D A P S A
Disease Acti vit y i n Ps oriatic Art hritis
D M A R D
Disease -M o dif y i n g A ntir he u matic Dr u g
D M P
data ma na ge me nt p la n
e C R F
electr o nic case re p ort f or m
E D C
electr o nic data ca pt ure
E D P
e x p os ure d uri n g pre g na nc y
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 6 of 5 9
A b bre vi ati o n
Defi niti o n
E M A
E ur o pea n Me dici nes A ge nc y
E N R
all e nr olle d set
E S R
er yt hr oc yte se di me ntati o n rate
E U
E ur o pea n U ni o n
E U L A R
E ur o pea n Lea g ue A gai nst R he u matis m
F A S
f ull a nal ysis set
G P P
g o o d p har mac oe pi de mi ol o g y practice
H A Q -DI
Healt h Assess me nt Q uesti o n naire – Disa bilit y I n de x
H b A 1 C
he m o gl o bi n A 1 C
H D L
hi g h -de nsit y li p o pr otei n
I B M-C D
I nter nati o nal B usi ness Mac hi nes Cli nical
De vel o p me nt
I CF
i nf or me d c o nse nt f or m
IE C
I n de pe n de nt Et hics C o m mittee
I F N
i nterfer o n ga m ma
I L
i nterle u ki n
I SP E
I nter nati o nal S ociet y f or P har mac oe pi de mi ol o g y
I RB
I nstit uti o nal Re vie w B oar d
J A K
Ja n us ki nase
JIA
j u ve nile i di o pat hic art hritis
L D A
l o w disease acti vit y
L D I
Lee ds Dact y litis I nde x
L D L
l o w-de nsit y li p o pr otei n
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 7 of 5 9
A b bre vi ati o n
Defi niti o n
L E I
Lee ds E nt hesitis I n de x
M D A
mi ni m u m disease acti vit y
Me d D R A
Me dical Dicti o nar y
f or Re g ulat or y Acti vities
M T X
met h otre xate
NI S
n o n -i nter ve nti o nal st u d y
N R S
N u merical Rati n g Scale
N S T E MI
n o n -S T -ele vati o n m yocar dia l i nfarcti o n
P A S D A S
Ps oriatic Art hritis Disease Acti vit y Sc ore
P A SI
Ps oriasis Area a n d Se verit y I n de x
P D E 4
p h os p h o diesterase 4
P R O
patie nt re p orte d o utc o me
Ps A
ps oriatic art hritis
Ps AI D 1 2
Ps oriatic Art hritis I mpact of Disease 1 2 Q uesti o ns
P V
p har mac o vi gila nce
Q o L
q ualit y of life
R A
r he u mat oi d art hritis
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S A S
Statistical A nal y sis S oft ware
S F -3 6
S h ort F or m 3 6
SJ C
s w olle n j oi nts c o u nt
S m P C
s u m mar y of pr o d uct c haracteristics
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 8 of 5 9
A b bre vi ati o n
Defi niti o n
S P A R C C -EI
S p o n d y loart hritis Researc h C o ns orti u m of Ca na da
E nt hesitis I nde x
S S Z
salaz o p yri ne
S T E MI
S T -ele vati o n m yocar dial i nfarcti o n
T h
T- hel per (cell)
TJ C
te n der j oi nts c o u nt
T N Fi
t u m or necr osis fact or i n hi bit ors
ts D M A R D
tar gete d s ynt hetic Disease -M o dif y i n g A ntir he u matic
Dr u g
U A
uric aci d
V A S
Vis ual A nal o g ue Scale
V T E
ve n o us t hr o m b oe m b olis m
W H O
W orl d Healt h Or ga nizati o n
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 9 of 5 9
3. R E S P O N SI B L E P A R TI E S
Pri nci p al I n vesti g at or (s) of t he Pr ot oc ol
N a m e, de gree(s)
J o b Title
Affili ati o n
A d dress
Pr of. Ori El ka y a m
Hea d,
R he u mat ol o g y
I nstit ute
Tel A vi v S o uras k y
Me dical Ce nter
Weis ma n
6, Tel
A vi v, Israel
Dr. Merie m
Kess o uri
N o n -I nter ve nti o nal
St u d y Lea d
Pfizer Fra nce
2 3 - 2 5 A ve n ue d u
D octe ur
La n nel o n g ue
Paris, Fra nce
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 0 of 5 9
4. A B S T R A C T
Sta n d Al o ne D oc u me nt
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 1 of 5 9
5. A M E N D M E N T S A N D U P D A T E S
A m e n d me nt 
n u m ber
D ate 
Pr ot oc ol 
secti o n(s) 
c h a n ge d
S u m m ar y of 
a m e n d me nts(s)
Re as o n
1
1 4 Fe br uar y 
2 0 2 3
Secti o n 4. 
A bstract
Ali g ne d wit h c ha n ges t o 
mai n te xt.
C o nsiste nc y.
Secti o n 6. 
Milest o nes
C ha n ge d dates of e n d of dat a 
c ollecti o n a n d fi nal st u d y 
re p ort.
A d de d ac t ual start of data 
c ollecti o n.
E nr ol me nt peri o d e xte n de d 
b y 8 m o nt hs.
Secti o n 7. 
Rati o nale a n d 
Bac k gr o u n d
A d de d ne w f or m ulati o n of 
1 1 m g e xte n de d release.
U p date d S m P C a n d 
rec o m me n de d d ose.
Secti o n 9. 1. 
St u d y Desi g n
C ha n ge d t he patie nt n u m ber 
fr o m ‘ 50 0 ’ t o ‘ 2 0 0’ i n Fi g ure 
1.
T o reflect c ha n ge i n sa m ple 
size.
Secti o n 9. 2. 
Setti n g
C ha n ge d pla n ne d e nr ol lme nt
t o 2 0 0 patie nts, u p date d 
c o u ntr y list, c ha n ge d 
e nr ol me nt peri o d t o 2 5
m o nt hs, a n d t otal st u d y 
d urati o n t o 3 7 m o nt hs.
C ha n ge d e nr ol me nt 
pr ojecti o ns a n d e xte n de d 
e nr ol me nt peri o d.
Secti o n 9. 4. 
Data S o urces
Clarifie d t hat I Q VI A will 
e nter P R Os i nt o t he E D C 
rat her t ha n t he sites.
C ha n ge i n pr oce d ure.
C orrecte d n o n -o bser vati o nal 
t o n o n-i nter ve nti o nal
T y p o.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 2 of 5 9
A m e n d me nt 
n u m ber
D ate 
Pr ot oc ol 
secti o n(s) 
c h a n ge d
S u m m ar y of 
a m e n d me nts(s)
Re as o n
Secti o n 9. 4. 2. 
P R Os
A d de d te xt descri bi n g t he 
Ps oriatic Art hri tis I m pact of 
Disease 1 2 q uesti o n naire. 
T o ali g n wit h t he list of 
varia bles i n secti o n 9. 3
Secti o n 9. 5. 
St u d y Size
U p date d e nr ol me nt t o 2 0 0 
patie nts, e x pecte d e val ua ble
patie nts t o 1 5 4 pa tie nts, a n d 
precisi o n esti mate t o 6. 3 %.
T o reflect c ha n ges i n 
enr ol me nt pr ojecti o ns.
Secti o n 1 0. 4
A d di n g t hat d ue t o t he 
o bser vati o nal nat ure of t his 
st u d y, I R B/I E C a p pr o val is 
n ot re q uire d i n De n mar k
Clarificati o n.
Secti o n 1 1
U p dati n g t he n o n -serio us 
A d vers e E ve nt t o be 
re p orte d t o Pfizer safet y.
Ne w  te xt a d de d re gar di n g 
e x p os ure d uri n g pre g na nc y
T he pre vi o us list is n ot 
re prese ntati ve of A E SI, b ut 
t he ris k cate g or y.
Clarif yi n g w hat e ve nts ar e 
re p orta ble d uri n g pre g na nc y
A n ne x 2
A N N E X 2. E N C E P P 
C H E C K LI S T F O R S T U D Y 
P R O T O C O L S
Re m o ve d a n ne x as E N Ce P P 
c hec klist n ot re q uire d.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 3 of 5 9
6. MI L E S T O N E S
Milest o ne
Pl a n ne d d ate
Pla n ne d start of data c ollecti o n
3 1 A u g ust 2 0 2 0
Act ual start of data c ollecti o n
1 7 Ma y  2 0 2 1
E n d of data c ollecti o n
2 2 J ul y  2 0 24
Fi na l st u d y rep ort
2 2 N o ve m ber 2 0 2 4
7. R A TI O N A L E A N D B A C K G R O U N D
Ps oriatic art hritis ( Ps A) is a c hr o nic pr o gressi ve i nfla m mat or y disease i n v ol vi n g s ki n
( ps oriasis), nails, a n d j oi nts ( peri p heral as well as s o meti mes s pi nal). I nv ol ve me nt of t he
m usc ul os keletal s yste m i n PsA ma y ca use i nfla m mati o n of j oi nts, periartic ular tiss ues
(e nt hesitis, te nos y n o vitis, dact y litis), a n d s pi ne (sacr oiliitis a n d/ or s p o n d ylitis) a n d
irre versi ble artic ular a n d periartic ular str uct ural da ma ge. Ps A has a si g nifica nt ne gati ve
i m pact on t he pati e nt’s ge neral c o n diti o n, m o o d, a n d q ualit y of life ( Q o L) wit h pr o gressi ve
disa bilit y if u ntreate d. T he pre vale nce of Ps A is esti mate d t o be u p t o 1 % of t he ge neral 
p o p ulati o n, a n d it is m o re pre vale nt a m o n g patie nts wit h ps oriasis, ra n gi n g fr o m 6% t o 
4 2 %. 1 -6
Ps A is ofte n acc o m pa nie d wit h m ulti ple c o- m or bi dities s uc h as dia betes mellit us, o besit y , 
n o nal c o h olic fatt y li ver disease, meta b olic s y n dr o me, g o ut, h y p erte nsi o n, m o o d dis or ders, 
a n d fi br o m yal gia. 7 -1 1 Ps A prese nts si g nifica nt healt h a n d s oci oec o n o mic b ur de ns f or t he 
i n di vi d ual a n d s ociet y. T here is c urre ntly n o c ure f or Ps A. The p ur p ose of treat me nt is t o 
c o ntr ol disease acti vit y, alle viate si g ns a n d sy m pt o ms, mai ntai n p h y sical f u ncti o n, o pti mize 
Q o L , a n d, if p ossi ble, i n d uce c o m plete re missi o n.1 2
C urre ntl y , t here are n o widel y  a greed u p o n defi niti o ns of disease se verit y  i n Ps A a n d it is 
j u d ge d o n a case-b y -case basis b y patie nts a n d healt h care pr o vi ders. H o we ver, se verit y is 
assesse d usi n g b ot h le vel of disease acti vit y  at a gi ve n ti me p oi nt, a n d t he prese nce or 
a bse nce of p o or pr o g n ostic fact ors a n d l o n g -ter m da ma ge. I n cli nical trials, se vere ps oriasis 
has bee n defi ne d as a Ps oriasis Area a n d Se verit y  I n de x ( P A SI) sc ore of ≥1 2 a n d a B o d y  
S urface Area ( B S A) sc ore of ≥1 0. 1 3
T here is relativel y  little e xisti n g e vi de nce t o s u p p ort t he effecti ve ness of c o n ve nti o nal 
s ynt hetic Disease -M o dif y i n g A ntir he u matic Dr u gs (cs D M A R Ds) i n Ps A (e g, met h otre xate 
[ M T X], salaz o p yri ne [ S S Z]). T he cs D M A R Ds d o n ot a p pear t o c o nsiste ntl y sl o w or pre ve nt 
pr o gressi v e j oi nt da ma ge, a n d dr u g i nt olera nce a n d safet y iss ues are ofte n prese nt. 1 4 -1 6
Use of bi ol o gical Disease -M o dif y i n g A ntir he u matic Dr u gs ( b D M A R Ds) re mai ns limite d 
wit h t he i nc o n ve nie nce of t he re q uire d r o utes of pare nteral a d mi nistrati o n (i ntra ve n o us 
i nf usi o ns or s u bc uta ne o us i njecti o ns) a n d a p pare nt l oss of i nitial effecti ve ness wit h c o nti n ue d 
use i n a si g nifica nt pr o p orti o n of patie nts. 1 4 -1 6 I n p u blis he d st u dies, t u m or necr osis fact or 
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 4 of 5 9
i n hi bit ors ( T N Fi) ha ve de m o nstrate d b ot h effecti ve ness (re d ucti o n of j oi nt disease acti vit y,
ps oriasis s ki n i m pr o ve me nt, a n d retar dati o n o f j oi nt dama ge) a n d acce pta ble safet y .1 4 -1 6 Ne w
b D M A R Ds ha ve bee n i ntr o d uce d, s uc h as a nti-i nterle u ki n (I L)-1 2/I L - 2 3 p 4 0 c o m m o n
s u b u nit uste ki n u ma b, a nti-I L- 1 7 A sec u ki n u ma b a n d i xe kiz u ma b, a n d selecti ve T- cell c o-
sti m ulati o n m o d ulat or a batace pt. 1 7 Rece ntl y , effecti ve ness of I L -2 3/ 1 2 a n d I L - 1 7 
i nfla m mat or y a xis dr u gs was de m o nstrate d i n Ps A. Treat me nt fail ure wit h t hese dr u gs ca n 
re prese nt a si g nifica nt cli nical pr o ble m a n d treat me nt wit h t hese a ge nts ca n be hi n dere d i n 
dail y  cli nical practice b y t he prese nce of c o-m or bi di ties, s uc h as n o nalc o h olic 
steat o he patitis.1 8
T heref or e, t here is a p ot e ntial u n met me dical nee d f or ne w Disease- M o dif yi n g A ntir he u matic 
Dr u gs ( D M A R Ds) i n t he Ps A patie nt p o p ulati o n. 1 4 -1 6 T he disc o ver y of pr o -i nfla m mat ory 
i ntracell ular pat h wa ys i n v ol ve d i n Ps A pat h o ge nesis, s uc h as tra nscri pti o n fact ors Ja n us 
ki nase (J A K) has le d t o t he de vel o p me nt of differe nt tar gete d s y nt hetic Disease -M o dif y i n g 
A ntir he u matic Dr u gs (ts D M A R Ds). A pre milast ( Otesla ®, P D E 4 [ p h os p h o diesteras e 4] 
i nhi bit or) a n d t ofaciti ni b ( Xelja nz ®, J A K i n hi bit o r) are t he o nl y ts D M A R Ds a p pr o ve d i n t he 
treat me nt of Ps A.
T ofaciti ni b ( C P -6 9 0, 5 5 0) is a n oral J A K i n hi bit or t hat tar gets i nfla m mati o n b y  re d uci n g 
pr o - i nfla m mat or y c yt o ki ne si g nali n g a n d pr o d ucti o n.1 9 T ofaciti ni b is i n dicate d f or t he 
treat me nt of i nfla m mat or y diseases i ncl u di n g r he u mat oi d art hritis ( R A), Ps A, a n d ulcerati ve 
c olitis. 
T ofaciti ni b i n c o m bi nati o n wit h M T X is i n dicate d f or t he treat me nt of acti v e Ps A in a d ult 
patie nts w h o ha ve ha d a n i na de q uate res p o nse or w h o ha ve bee n i nt olera nt t o a pri or 
D M A R D t hera p y, t he rec o m me n de d d ose is 5 m g a d mi nistere d t wice dail y or 1 1 m g
pr ol o n ge d release ta blets a d mi nistere d o nce dail y (s u m mar y of pr o d uct c haracteristics 
[ S m P C] date d 1 4 Dece m ber 2 0 2 1 [ E M A/ 1 0 3 8 9 8/ 2 0 1 7]).2 0 T he use of t ofaciti ni b is 
c o ntrai n dicate d i n patie nts wit h h y perse nsiti vit y  t o t he acti ve s u bsta nce or t o a n y of t he 
e xci pie nts, acti ve t u bercul osis, seri o us infecti o ns s uc h as se psis or o p p o rt u nistic i nfecti o ns, 
se vere he patic i m pair me nt, pre g na nc y, a n d lactati o n.2 0
T ofaciti ni b acts i nsi de t he cell b y prefere ntiall y i n hi biti n g si g nali n g b y  c yt o ki ne rece pt ors 
ass ociat e d wit h J A K 1 or J A K 3. 2 1 I nhi biti o n of J A K 1 a n d J A K 3 b y  t ofaciti ni b bl oc ks 
si g nali n g t hr o u g h t he c o m m o n ga m ma c hai n c ontai ni n g rece pt ors f or se veral c y t o ki nes, 
i ncl u di n g 
I L - 2, - 4, - 7, - 9, - 1 5, a n d - 2 1. T hese c yt o ki nes are i nte gral t o l ym p h oc y te acti vati o n, 
de vel o p me nt, h o me ostasis, pr oliferati o n, a n d f u ncti o n; t heref ore, i n hi biti o n of t heir si g nali n g 
ma y  res ult i n t he mo d ulati o n of m ulti ple as pects of t he i m m u ne res p o nse. I n a d diti o n, 
i n hi biti o n of J A K 1 will res ult i n atte n uati o n of si g nali n g b y a d diti o nal pr o -i nfla m mat or y 
c yt o ki nes, s uc h as I L- 6 a n d i nterfer o n ga m ma (I F Nγ).2 2 ,2 3 I n a d diti o n t o i nterferi n g wit h T-
h el per ( T h)1 a n d T h 2 cell differe ntiati o n, t ofaciti ni b has bee n s h o w n t o i nterfere wit h t he 
pr o d ucti o n of i nfla m mat or y  T h 1 7 cells.2 4 T hese effects pr o vi de t he basis f or use i n diseases 
i n w hic h t he i m m u ne res p o nse pla ys a pat h o ge nic r ole s uc h as R A a n d Ps A. 2 5 ,2 6
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 5 of 5 9
T he effecti ve ness of t ofaciti ni b was de m o nstrate d i n 2 P hase 3 ra n d o mize d, d o u b le-bli n d, 
place b o -c o ntr olle d cli nical trials (N C T 0 1 8 7 7 6 6 8 [ O P A L  B R O A D E N: 4 2 2 patie nts e nr olle d] 
a n d N C T 0 1 8 8 2 4 3 9 [ O P A L B E Y O N D: 3 9 5 patie nts e nr olle d]) t hat e nr olle d a d ult patie nts 
wit h acti ve Ps A at scree ni n g a n d baseli ne, a n d wit h i na de q uate res p o nse t o pr i or 
cs D M A R Ds. N C T 0 1 8 7 7 6 6 8 e nr olle d 4 2 2 Ps A pat ie nts naï ve t o T N Fi b ut all o wi n g 
c o nc urre nt treat me nt wit h M T X, lefl u n o mi de, or s ulfasalazi ne, a n d ha d 1 2 m o nt hs of t otal 
f oll o w- u p; a n d N C T 0 1 8 8 2 4 3 9 e nr olle d 3 9 5 Ps A patie nts wit h i na de q uate res p o nse or lac k of
t olerati o n t o pre vi o usl y a d mi nistere d T N Fi a n d ha d 6 m o nt hs of t otal f oll o w -u p. B ot h st u dies 
ha d c ha n ge i n A merica n C olle ge of R he u mat ol o g y  ( Criteria) 2 0 % ( A C R 2 0) a n d Healt h 
Assess me nt Q uesti o n naire - Disa bilit y  In de x ( H A Q -DI ) at M o nt h 3 as pri mar y e n d p oi nts, a n d 
s h o we d s u peri or efficac y o ver place b o at 3 m o nt hs of treat me nt. 2 7 ,2 8 I n b ot h st u dies, a d verse 
e ve nts ( A Es) were c o m para ble t o t h ose o bser ve d i n R A st u dies. T o date, t ofaciti ni b is t he 
o nl y J A K i n hi bit or t hat has bee n a p pr o ve d f or t he treat me nt of Ps A b y t he U nite d States 
F o o d a n d Dr u g A d mi nistrati o n (a p pr o ve d 1 4 Dece m ber 2 0 1 7) a n d t he E ur o pea n C o m missi o n 
(a p pr o ve d 2 8 J u ne 2 0 1 8). 1 7
Cli nical trial res ults reflect res p o nses i n selecte d p o p ulati o ns, ofte n e xcl u di n g patients wit h 
si g nifica nt c o-m or bi dities. E val uati o n of R A patie nts e nr olle d i n a disease re gistr y  a n d w h o 
were treate d wit h a T N Fi esti mate d t hat o nl y  2 1-3 3 % of patie nts w o ul d ha ve met t h e 
eli gibilit y  criteria of maj or trials. Re gistr y patie nts t hat were c o nsidere d i neli gi ble f or t he 
cli nical trials ha d l o wer baseli ne disease acti vit y , m ore c o m or bi dit y, a n d l o wer f u ncti o nal 
stat us.2 9 T his st u d y  will e v al uate t he effecti ve ness of t ofaciti ni b i n Ps A patie nts i n a real-
w orl d setti n g o ver a 1 2- m o nt h peri o d.
8. R E S E A R C H Q U E S TI O N A N D O B J E C TI V E S
8. 1. Rese arc h Q uesti o n
T he ai m of t his st u d y is t o e val uate t he effecti ve ness of treat me nt wit h t ofaciti ni b o n diseas e 
acti vit y, re missi o n, a n d Q o L i n patie nts wit h Ps A, o ver a 1 2-m o nt h o bser vati o n peri o d.
8. 2. O bjecti ves
Pri m ary O bjective

T o e val uate t he pr o p orti o n of patie nts ac hie vi n g l o w disease acti vit y ( L D A) after 
6 m o nt hs of f oll o w - u p.
Sec o n d ary O bjectives

T o e val uate t he pr op orti o n of patie nts ac hie vi n g L D A after 3 a n d 1 2 m o nt hs of 
f oll o w- u p.

T o e val uate t he pr o p orti o n of patie nts ac hie vi n g mi ni m u m disease acti vit y ( M D A) 
after 3, 6, a n d 1 2 m o nt hs of f oll o w - u p.

T o e val uate t he pr o p orti o n of patie nts ac hie vi n g re missi o n after 3, 6, a n d 12 m o nt hs
of f oll o w - u p.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 6 of 5 9

T o e val uate c ha n ge fr o m baseli ne i n Ps oriatic Art hritis I mpact of 
Disease 1 2 Q uesti o ns ( Ps AI D 1 2) sc ore after 3, 6, a n d 1 2 m o nt hs of f oll o w - u p.

T o e val uate c ha n ge fr o m baseli ne i n S p o n d y lart hritis Researc h C o ns orti u m of Ca na da 
E nt hesi tis In de x ( S P A R C C-EI ) sc ore after 3, 6, a n d 1 2 m o nt hs of f oll o w- u p.

T o i de ntif y pr o g n ostic i n dicat ors f or ac hie vi n g L D A after 3, 6, a n d 1 2 m o nt hs of 
f oll o w- u p.

T o e val uate c ha n ge fr o m baseli ne i n Q o L s c ores after 3, 6, a n d 1 2 m o nt hs of f oll o w-
u p.
E x pl or at o ry O bjectives
T o e val uate c ha n ges i n meas ures of disease acti vit y ( Ps oriatic Art hritis Disease Acti vit y  
Sc ore [ P A S D A S] a n d Disease Acti vit y i n Ps oriatic Art hritis [ D A P S A]) fr o m baseli ne after 3, 
6, a n d 1 2 m o nt hs of f oll o w - u p.
9. R E S E A R C H M E T H O D S 
9. 1. St u d y D esi g n
T his is a pr os pecti ve, n o n- i nter ve nti o nal, m ulti nati o nal, m ulti-ce nter st u d y t o e val uate t he 
effecti ve ness of t ofaciti ni b i n patie nts wit h Ps A i n r o uti ne cli nical practice wit h u p t o
1 2 m o nt hs of f oll o w-u p. Patie nts m ust be treat me nt naï ve f or t ofaciti nib at t he ti me of 
e nr oll me nt.
All assess me nts descri be d i n t his pr ot oc ol are perf or me d as part of r o uti ne cli nical practice or 
f oll o wi n g sta n dar d practice g ui deli nes, f or t he patie nt p o p ulati o n a n d healt hcare pr o vi der 
s pecialt y i n t he c o u ntries w here t his n o n- i nter ve nti o nal st u d y is bei n g c o n d ucte d. T he 
me dici nal pr o d uct(s) will be prescri be d i n r o uti ne cli nical care i n acc or da nce wit h t he ter ms 
of l ocal c o u ntr y rei m b urse me nt g ui deli nes. N o st u d y  dr u g will be pr o vi de d as a part of t his 
st u d y, a n d this pr ot oc ol d oes n ot rec o m me n d t he use of a n y  s pecific treat me nts. T he 
assi g n me nt of t he patie nts t o a partic ular t hera pe utic strate g y  is n ot deci de d b y t his pr ot oc ol 
b ut falls wit hi n c urre nt practice a n d t h e cli nical decisi o n f or t he prescri pti o n of t ofa citi ni b 
s ho ul d be clearl y se parate d fr o m t he decisi o n t o i ncl u de t he patie nt i n t he st u d y . D ose a n d 
d urati o n of treat me nt s h o ul d be base d o n cli nical a n d i n di vi d ual nee ds a n d are deter mi ne d b y  
t he treati n g p hys icia n.
N o a d diti o nal dia g n ostic or m o ni t ori n g pr oce d ures are ma n date d, a n d f oll o w- u p visits are 
ca pt ure d as part of n or mal me dical practice. E pi de mi ol o gical met h o ds will be use d f or t he 
a nal ys is of c ollecte d data. Patie nts will be f oll o we d u p d uri n g r o uti ne cli nic visits c o nsiste nt 
wit h t he E ur o pea n L ea g ue A gai nst R he u matis m ( E U L A R) g ui deli nes f or f oll o w -u p of 
patie nts wit h Ps A ( Fi g ure 1 ). D oc u me nte d visits f or t he pur p ose of t his st u d y  will be at 
e nr oll me nt, t he n at a p pr o xi matel y M o nt hs 3 ( visit 2), 6 ( visit 3), a n d 1 2 ( visit 4, e n d of st u d y  
visit) f oll o wi n g i nitiati o n of treat me nt wit h t ofaciti ni b. Patie nts t hat per ma ne ntl y  disc o nti n ue 
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 7 of 5 9
treat me nt wit h t ofaciti ni b will be disc o nti n ue d fr o m t he st u d y. St u d y f oll o w-u p will st o p at 
M o nt h 1 2 u nless a patie nt has alrea d y disc o nti n ue d.
Fi g ure 1 .
St u d y Desi g n
Start of d oc u me ntati o n
E n d of d oc u me ntati o n 
E nr oll me nt
M o nt h 3
M o nt h 6
M o nt h 1 2 
A p pr o xi m ate sc he d ule of pl a n ne d visits
9. 1. 1. E n d p oi nts
Pri m ary e n d p oi nt

Pr o p orti o n of patie n ts ac hie vi n g L D A defi ne d as P A S D A S sc ore ≤3. 2 at M o nt h 6.
Sec o n d ary e n d p oi nts

Pr o p orti o n of patie nts ac hie vi n g L D A defi ne d as P A S D A S sc ore ≤3. 2 at M o nt hs 3
a n d 1 2.

Pr o p orti o n of patie nts ac hie vi n g M D A defi ne d as at least 5 of 7 criteria (see Ta ble 3 )
met at M o nt hs 3, 6, a n d 1 2.

Pr o p orti o n of patie nts ac hie vi n g re missi o n defi ne d as P A S D A S sc ore ≤1. 9 at M o nt hs 
3, 6, a n d 1 2.

Pr o p orti o n of patie nts ac hie vi n g re missi o n defi ne d as D A P S A sc ore ≤4. 0 at M o nt hs 
3, 6, a n d 1 2.

C ha n ge fr o m basel i ne i n Ps AI D 1 2 sc ore at M o nt hs 3, 6, a n d 1 2.

C ha n ge fr o m baseli ne i n S P A R C C -EI  sc ore at M o nt hs 3, 6, a n d 1 2.

Pr o p orti o n of patie nts ac hie vi n g L D A at M o nt hs 3, 6, a n d 1 2 base d o n prese nce of 
pr o g n ostic fact ors liste d i n Sect i o n 9. 4. 3 .

C ha n ge fr o m baseli ne i n Q o L usi n g patie nt re p orte d o utc o me ( P R O) sc ores at M o nt hs 
3, 6, a n d 1 2.
A p pr o xi m atel y 2 0 0 p atie nt s o n t of aciti ni b
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 8 of 5 9
E x pl or at ory e n d p oi nts

C ha n ge fr o m baseli ne i n P A S D A S sc ores at M o nt hs 3, 6, a n d 1 2.

C ha n ge fr o m baseli ne i n D A P S A sc ores at M o nt hs 3, 6, a n d 1 2.
9. 2. Setti n g
T his st u d y  will e nr oll a p pr o xi matel y 2 0 0 patie nts fr o m r he u mat ol o gists a n d/ or Ps A s pecialist 
ce nters i n 8 c o u ntries ( Bel gi u m, De n mar k, Fi nla n d, Fra nce, Israel, Ne t herla n ds, S pai n, a n d 
S we de n ) o ver a n e nr oll me nt peri o d of 2 5 m o nt hs. T he c o u ntries liste d a b o ve are a ntici pate d 
t o partici pate i n t his st u d y, h o we ver a d diti o nal c o u ntries ma y be i ncl u de d at a later ti me. 
Eac h patie nt will ha ve u p t o 1 2 m o nt hs of f oll o w-u p f or a t o tal st ud y  d urati o n of 3 7 m o nt hs.
C o nsec uti ve patie nts atte n di n g a r o uti ne cli n ical visit will be i n vite d t o partici pate if t he y 
meet t he eli gi bilit y  criteria f or t he st u d y a n d are t o start o n treat me nt wit h t ofaciti ni b f or 
acti ve Ps A. A n e nr oll me nt/s cree ni n g l o g will be mai ntai ne d b y  t he sites t o rec or d basic 
de m o gra p hics a n d reas o ns f or n o n -e nr oll me nt f or patie nts t hat c h o ose n ot t o e nr oll.
All visits s hall be sc he d ule d acc or di n g t o l ocal cli nical practice. Wit hi n t his st u d y, a t otal of 
4 visits are i ncl u ded: at e nr oll me nt, t he n at a p pr o xi matel y  M o nt h 3, M o nt h 6, a n d M o nt h 1 2 
f oll o wi n g i nitiati o n of treat me nt wit h t ofaciti ni b. All patie nts will be f oll o we d fr o m 
e nr oll me nt u ntil t he e n d of f oll o w -u p (i ncl u di n g disc o nti n ua ti o ns), deat h, l oss t o f oll o w- u p, 
or w it h dra wal of c o nse nt ( w hic he ver occ urs first).
9. 2. 1. I ncl usi o n Criteri a
Patie nt eli gi bilit y s h o ul d be re vie we d by a n I n vesti gat or bef ore patie nts are i ncl u de d i n t he
st u d y. Patie nts m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble f or i nclusi o n i n
t he st u d y:
1.
Patie nts a ge d ≥1 8 ye ars.
2.
M o derate t o se vere Ps A disease ac ti vit y dia g n ose d.
3.
Patie nts f or w h o m t he p h ysicia n’s decisi o n has bee n ma de t o i nitiate treat me nt wit h 
t ofaciti ni b, i n us ual cli nical practice c o n diti o ns a n d i n c o m plia nce wit h t he l ocal la bel.
4.
Patie nts are treat me nt naï ve t o t ofaciti ni b o n t he date of pr o v i di n g i nf or me d c o nse nt.
5.
E vi de nce of a pers o nall y si g ne d a n d date d i nf or me d c o nse nt d oc u me nt i n dicati n g t hat 
t he patie nt ( or a le gall y acce pta ble represe ntati ve) has bee n i nf or me d of all perti ne nt 
as pects of t he st u d y.
6.
Patie nts o n D M A R Ds m ust ha ve n ot ha d a treat me nt c ha n ge i n t he past 3 m o nt hs.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 1 9 of 5 9
9. 2. 2. E xcl usi o n Criteri a
Patie nts meeti n g a n y of t he f oll o wi n g criteria will n ot be i ncl u de d i n t he st u d y:
1.
C o ntra i n dicati o ns acc or di n g t o t he Xelja nz ® (t ofaciti ni b) prescri bi n g i nf or mati o n.
2.
Recei pt of a n y i n vesti gati o nal dr u g wit hi n 3 m o nt hs bef ore st u d y i ncl usi o n.
3.
Patie nt is pre g na nt or breastfee di n g.
4.
Rece nt her pes z oster i nfecti o n ( wit hi n past 6 m o nt hs) or hist or y of se vere 
disse mi nate d her pes z oster i nfecti o n.
5.
Acti ve treat me nt f or a mali g n a nc y.
6.
C o nc o mita nt treat me nt wit h bi ol o gical Disease -M o dif y i n g A ntir he u matic Dr u gs 
( b D M A R D).
9. 3. V ari a bles
T he Sc he d ule of Acti vities (Ta ble 1) pr o vi des a n o ver vie w of t he re q ueste d data t o be
c ollecte d at eac h visit, wit h f urt her details descri be d bel o w.
T a ble 1. Sc he d ule of Acti vities
A p pr o xi m ate sc he d ule of pl a n ne d visits
E nr oll me nt
( Visit 1)
M o nt h 3 
( Visit 2)
M o nt h 6
( Visit 3)
M o nt h 1 2 
( Visit 4)
I nf or me d c o nse nt
X
Eli gi bilit y
X
De m o gra p hics
X
Ps A disease hist o r y
X
Me dical hist or y
X
Pre vi o us Ps A treat me nts
X
C o -m or bi dities
X
X
C o nc o mita nt Ps A treat me nts
X
X
X
X
T ofaciti ni b treat me nt
X
X
X
X
P h ysical e xa mi nati o n 1
X
X
X
X
Bl o o d bi oc he mistr y/ he mat ol o g y 2
X
X
X
X
I nfla m mat or y mar kers 3
X
X
X
X
Disease acti vit y meas ures 4
X
X
X
X
Patie nt re p orte d o utc o mes 5
X
X
X
X
E n d of st u d y
X
A d verse e ve nts
C o nti n u o us
A b bre viati o ns: Ps A = Ps oriati c Art hritis.
1.
Hei g ht ( o nl y c ollecte d at e n roll me nt ), wei g ht, calc ulate d b o d y mass i n de x, waist circ u mfere nce, s m o ki n g stat us
(c urre nt/ q uit < 1 yr/f or mer/ ne ver/ u n k n o w n).
2.
C o m plete bl o o d c o u nt ( C B C), creati ni ne, uric aci d ( U A), al kali ne p h os p hatase ( A L K P H), as partate tra nsa mi nase ( A S T), 
ala ni ne tra nsa minase ( A L T), gl uc ose, he m o gl o bi n A 1 C ( H b A 1 C), t otal c h olester ol, tri gl yceri des,
l o w-de nsit y li p o pr otei n ( L D L), hi g h - de nsit y li p o pr otei n ( H D L).
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 0 of 5 9
3.
Er yt hr oc yte se di me ntati o n rate ( E S R), C -reacti ve pr otei n ( C R P).
4.
S w o lle n j oi nt c o u nt ( SJ C 6 6), te n der j oi nt c o u nt ( TJ C 6 8), Patie nt Gl o bal Assess me nt, P h ysicia n Gl o bal Assess me nt, Patie nt Pai n
Assess me nt, Lee ds E nt hesitis I n de x ( L EI), Lee ds Dact ylitis I n de x ( L DI), te n der e nt hesial p oi nts, Ps oriasis Ar ea a n d Se verit y 
I n de x ( PA S I), B o d y S urface Area ( B S A), S p o n d yl oart hriti s Researc h C o ns orti u m of Ca na da E nt hesitis I n de x ( S P A R C C-
EI), a n d ra di ol o gical re p orts sc ore d usi n g S har pe -V a n de Heij de m o difie d
sc ori n g f or Ps A.
5.
S h ort F or m 3 6 ( S F-3 6), Healt h Assess me nt Q uesti o n naire – Di sa bilit y I n de x ( H A Q-DI), Ps oriatic Art hritis I mpact of Disease
1 2 Q uesti o ns ( Ps AI D 1 2).
9. 3. 1. E nr oll me nt V isit ( Visit 1)

I nf or me d C o nse nt.

I ncl usi o n/ E xcl usi o n criteria.

De m o gra p h y ( date of birt h, se x).

Ps A disease hist or y ( date of di a g n osis).

D urati o n of s y m pt o ms pri or t o e nr oll m e nt (ie, c urre nt e pis o de of s y m pt o ms [if
a p plica ble]).

Prese nce of r he u mat oi d n o d ules [ prese nt/a bse nt/ n ot a vaila ble].

Art hritis of ha n d j oi nts [ prese nt/a bse nt/ n ot a vaila ble].

C o u nts of j oi nts affecte d b y arthr itis at e nr oll me nt (s pecifie d b y: s mall j oi nts,
me di u m j oi nts, lar ge j oi nts, ha n d j oi nts).

U ne q ui v ocal ra di ol o gical er osi o n [ prese nt/a bse nt/ n ot a vaila ble].

U ne q ui v ocal b o n y decalcificati o n i n ha n d a n d wrist j oi nts [ prese nt/a bse nt/ n ot 
a vaila ble].

T ofaciti ni b d osi n g ( d osa ge, start date).

C o nc o mita nt Ps A treat ment ( ge neric na me, d osa ge, start/st o p dates, reas o n f or 
disc o nti n uati o n [if a p plica ble]).

Pri or treat me nt hist or y of Ps A ( ge neric na me, d osa ge, start/st o p dates, reas o n f or
disc o nti n uati o n [if a p plica ble ]).

Ot her rele va nt me dical hist or y a n d c o -m or bi dities (s pecif y, date of dia g n osis, e n d
date [if a p plica ble]), i ncl u di n g:

Hist or y  of ve n o us t hr o m b oe m b olis m ( V T E) ( date of e ve nt, t ype of e ve nt [ dee p 
ve n o us t hr o m b osis, p ul m o nar y e m b olis m]);
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 1 of 5 9

M y ocar dial i nfarct i o n wit hi n pre vi o us 3 m o nt hs ( date of e ve nt, t yp e of e ve nt
[ S T-ele vati o n m y ocar dial i nfarcti o n ( S T E MI), n o n -S T -ele vati o n m y ocar dial
i nfarcti o n ( N S T E MI), u n k n o w n]);

Dia g n osis of heart fail ure ( date of dia g n osis);

Dia betes ( date of dia g n osis, s pecif y [t ype 2 /t ype 1]);

H y perte nsi o n ( date of dia g n osis, treate d [ Yes/ N o/ u n k n o w n], treat me nt resista nt
[ Yes/ N o/ u n k n o w n]);

I n herite d c oa g ulati o n dis or der ( date of dia g n osis, s pecif y);

Mali g na nc y
( date of dia g n osis, s pecif y);

Use of c o m bi ne d h or m o nal c o ntrace pti ves or h o r m o ne re place me nt t hera py 
( ge neric na me, start/e n d dat e, reas o n f or disc o nti n uati o n [if a p plica ble]);

A n y ot her rele va nt me dical hist or y .

P h y sical e xa mi nati o n ( hei g ht, wei g ht, calc ulate d b o d y mass i n de x, waist
circ u mfere nce, s m o ki n g stat us [c urre nt/ q uit < 1 yr/ f or mer/ ne ver/ u n k n o w n]).

Bl o o d bi oc he mistr y  & he mat o l o g y (res ult, u nit, refere nce ra n ge [ w he n a p plica ble], 
cli nicall y si g nifica nt [ Yes/ N o]).

C o m plete bl o o d c o u nt ( C B C).

Creati ni ne, uric aci d ( U A), al kali ne p h os p hatase ( A L K P H), as partate
tra nsa mi nase ( A ST), ala ni ne tra nsa mi nase ( A L T), gl uc ose, he m o gl o bi n A 1 C 
( H b A 1 C), t otal c h olester ol, tri gl yceri des, l o w-de nsit y  li p o pr otei n ( L D L), hi g h-
de nsit y  li po pr otei n ( H D L).

I nfla m mat or y mar kers (res ult, u nit, refere nce ra n ge, cli nicall y si g nifica nt [ Yes/ N o]).

Er y t hr oc yte se di me ntati o n rate ( E S R).

C- reacti ve pr otei n ( C R P).

Disease acti vit y meas ures.

N u m ber of s w olle n a n d te n der j oi nts (s w olle n j oi nt c o u nt [ SJ C 66]/te n der j oi nt c o u nt 
[ TJ C 6 8]).

Patie nt Gl o bal Assess me nt.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 2 of 5 9

P h y sicia n Gl o bal Assess me nt.

Patie nt Pai n Assess me n t.

Lee ds E nt hesitis I n de x ( L EI).

Lee ds Dact yl itis I n dex ( L DI).

Te n der e nt hesial p oi nts.

P A SI .

B S A.

S p o n d y l oart hritis Researc h C o ns orti u m of Ca na da E nt hesitis I n de x ( S P A R C C-
EI ).

Ra di ol o gical re p orts sc ore d usi n g S har pe -Va n der Heij de m o difie d sc ori n g f or
Ps A. 3 0

P R O s.

S h ort F or m 3 6 ( S F -3 6).

H A Q -DI .

Ps AI D 1 2.
9. 3. 2. F oll o w -u p Visits 2, 3, 4 ( at a p pr o xi m atel y M o nt hs 3, 6, a n d 1 2)

T ofaciti ni b d osi n g ( d osa ge, start/st o p dates, reas o n f or disc o nti n uati o n [if 
a p plica ble]).

C o nc o mita nt Ps A treat me nt ( ge neric na me, d ose, start /st o p dates, reas o n f or 
disc o nti n uati o n [if a p plica ble]).

Rele va nt c o -m or bi dities (s pecif y, date of dia g n osis, e n d date [if a p plica ble]) at
M o nt h
6 o nl y .

P h y sical e xa mi nati o n ( wei g ht, calc ulate d b o d y mass i n de x, waist circ u mfere nce,
s m o ki n g stat us [c urre nt/ q uit < 1 y r/f or mer/ ne ver/ u n k n o w n]).

Bl o o d bi oc he mistr y & he mat ol o g y (res ult, u nit, refere nce ra n ge [if a p plica ble],
cli nicall y si g nifica nt [ Yes/ N o]).

C B C.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 3 of 5 9

Creati ni ne, U A, A L K P H, A S T, A L T, gl uc ose, H b A 1 C, t otal c h olester ol, 
tri glyceri des, L D L, H D L.

I nfla m mat or y ma r kers (res ult, u nit, refere nce ra n ge, cli nicall y si g nifica nt [ Yes/ N o]).

E S R.

C R P.

Disease acti vit y meas ures.

N u m ber of s w olle n a n d te n der j oi nts ( SJ C 6 6/ TJ C 6 8).

Patie nt Gl o bal Assess me nt.

P h y sicia n Gl o ba l Assess me nt.

Patie nt Pai n Assess me nt.

L EI.

L D I.

Te n de r e nt hesial p oi nts.

P A SI .

B S A.

S P A R C C -EI .

Ra di ol o gical re p orts sc ore d usi n g S har pe - Va n der Heij de m o difie d sc ori n g f or 
Ps A.

P R Os.

S F - 3 6.

H A Q -DI .

Ps AI D 1 2.

A Es.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 4 of 5 9
9. 3. 3. E n d of St u d y
T he f oll o wi n g a d diti o nal para m eters will be re q ueste d at t he e n d of st u d y vis it:

St u d y disc o nti n uati o n ( date of disc o nti n uati o n, reas o n f or st u d y disc o nti n uati o n);

T ofaciti ni b treat me nt stat us at disc o nti n uati o n;

Alter nati ve D M A R D treat me nt ( ge neric na me, d ose, start date).
9. 3. 4. Deri ve d V ar i a bles
T he st u d y e n d p oi nts are Ps A disease asse ss me nts, w hic h are deri ve d gl o bal sc ores fr o m
differe nt disease i n dicat ors. Ta ble 2 s h o ws t he disease i n dicat ors use d t o pre pare t he disease
assess me nt sc ores.
T a ble 2. Assess me nts Re q uire d f or Deri v a ti o n of St u d y E n d p oi nts
E n d p oi nts
Met h o d
P A S D A S  
D A P S A
M D A
L D A
re missi o n
P h ysicia n gl o bal assess me nt
V A S
x
Patie nt gl o bal assess me nt
V A S
x
x
x
Patie nt pai n assess me nt
V A S
x
S w olle n j oi nts c o u nt
e xa m
x
x
x
Te n der j oi nts c o u nt
e xa m
x
x
x
Te n d er e nt hesial p oi nts
e xa m
x
Lee ds e nt hesitis i n de x
e xa m
x
Lee ds dact ylitis i n de x
e xa m
x
P A SI (calc ulate d)
e xa m
x
B S A
e xa m
x
C R P
bl o o d
x
x
S F -3 6 ( p h ysical c o mp o ne nt)
P R O
x
H A Q -DI
P R O
x
P A S D A S sc ore
x ( ≤3. 2)
x ( ≤1. 9)
A b bre viati o ns: B S A = B o d y S urface Area, C R P = C- reacti ve pr otei n, D A P S A = Disease Acti vit y i n Ps oriatic
Art hritis, H A Q -DI = Healt h Assess me nt Q uesti o n naire - Disa bilit y I n de x, L D A = l o w disease acti vit y, 
M D A =
mi ni m u m disease acti vit y, P A S D A S = Ps oriatic Art hritis Disease Ac ti vit y Sc ore, P A SI = Ps oriasis A rea 
a n d Se verit y I n de x, P R O = patie nt re p orte d o utc o me, S F - 3 6 = S h ort F or m 3 6, V A S = Vis ual A nal o g ue Scale .
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 5 of 5 9
T a ble 3. C alc ul a ti o n of Dise ase Acti vit y I n dic at ors
Dise ase acti vit y 
i n dic at ors
Defi niti o n/ C alc ul ati o n
Ps oriatic Art hritis 
Disease Acti vit y Sc ore 
(P A S D A S) 3 1 -3 3
( 0. 1 8 × √p h ysicia n g l o bal assess me nt [ V A S, 0-1 0 0)
+ ( 0. 1 5 9 × √patie nt gl o bal assess me nt [ V A S, 0 -1 0 0])
– ( 0. 2 5 3 × √S F -3 6 – P h ysical c o m p o ne nt s u m mar y [ P R O])
+ ( 0. 1 0 1 × l n [ S w olle n j oi nt c o u nt [ SJ C 6 6] + 1])
+ ( 0. 0 4 8 × l n [ Te n der j oi nt c o u nt [ TJ C 6 8] + 1])
+ ( 0. 2 3 × l n [ Lee ds e nt hesitis c o u nt [ L EI] + 1])
+ ( 0. 3 7 7 × l n[ Lee ds dact ylitis c o u nt [ L DI] + 1])
+ ( 0. 1 0 2 × l n [ C R P ( m g/ L) + 1)] + 2) × 1. 5
P A S D A S sc ore r a n ge: 1 -1 0
N ote: P A S D A S V A S are b ase d o n a 1 0 0 m m sc ale
Disease Acti vit y i n 
Ps oriatic Art hritis 
( D A P S A)3 2 -3 4
S w olle n j oi nt c o u nt ( SJ C 6 6)
+ Te n der j oi nt c o u nt ( TJ C 6 8)
+ Patie nt gl o bal assess me nt [ V A S, 0 -1 0]
+ Patie nt pai n assess me nt [ V A S, 0-1 0]
+ C R P ( m g/ d L)
D A P S A sc ore r a n ge: 0- 1 6 4
N ote: D A P S A V A S are b ase d o n a 1 0c m sc ale
Mi ni m u m Disease 
Acti vit y ( M D A) 3 3 ,3 5
A patie nt is classifie d as i n M D A w he n t he y meet 5 of 7 of t he f oll o wi n g c riteria:

Te n der j oi nt c o u nt [ TJ C 6 6] ≤1

S w olle n j oi nt c o u nt [ SJ C 6 8] ≤1

P A SI ≤1 or B S A ≤3

Patie nt pai n assess me nt [ V A S, 0 -1 0 0] ≤1 5

Patie nt gl o bal assess me nt [ V A S, 0 -1 0 0] ≤2 0

H A Q - DI ≤0. 5

Te n der e nt hesial p oi nts ≤1
N ote: M D A V A S are b ase d o n a 1 0 0 m m sc ale
Ps oriasis A rea a n d 
Se verit y I n de x ( P A SI) 
F or eac h re gi o n: hea d, u p per li m b, tr u n k, l o wer li m bs
1.
B S A
2.
Pla q ue c haracteristics: er yt he ma + i n d urati o n/t hic k ness + scali n g
0 = N o ne
1 = Sli g ht
2 = M o derate
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 6 of 5 9
Dise ase acti vit y 
i n dic at ors
Defi niti o n/ C alc ul ati o n
3 = Se vere
4 = Ver y se vere
3.
Perce nta ge area affecte d:
0 = 0 %
1 = 1 % - 9 %
2 = 1 0 % - 2 9 %
3 = 3 0 % - 4 9 %
4 = 5 0 % - 6 9 %
5 = 7 0 % - 8 9 %
6 = 9 0 % - 1 0 0 %
Sc ore calc ulati o n:
F or eac h re gi o n: (s u m of pla q u e sc ores) × ( b o d y re gi o n B S A) × ( perce nt of area 
affecte d [ 0 -6])
P A SI sc ore = s u m of res ults o ver all 4 b o d y re gi o ns.
P A SI sc ore r a n ge: 0- 7 2
S p o n d yl oart hritis 
Researc h C o ns orti u m of 
Ca na da E nt hesitis I n de x
( S P A R C C-EI) 3 6
Cli nical e val uati o n of 1 6 sites:
Greater tr oc ha nter ( R/ L)
Q ua drice ps te n d o n i nserti o n i nt o t he patella ( R/ L)
Patellar li ga me nt i nserti o n i nt o t he patella a n d ti bial t u ber osit y ( R/ L)
Ac hilles te n d o n i nserti o n ( R/ L)
Pla ntar fascia i nserti o n ( R/ L)
Me dial e pic o n d yles ( R/ L)
Lateral e pic o n d yles ( R/ L)
S u pras pi nat us i nserti o n ( R/ L)
Te n der ness at eac h site is q ua ntifie d as: 0   =  n o n-te n der a n d 1   =  te n der.
S P A R C C -EI sc ore r a n ge: 0 – 1 6
Ps oriatic Art hritis I m pact 
of Disease 1 2 Q uesti o ns 
( Ps AI D 1 2)3 7
T he Ps AI D 1 2 calc ulati o n is base d o n N u meric Rati n g Scale ( N R S) q uesti o ns. 
Eac h N R S is assesse d as a n u m ber bet wee n 0 a n d 1 0. T he ra n ge of t he fi nal 
Ps AI D 1 2 val ue is 0 – 1 0 w here hi g her n u m bers i n dicate w orse stat us.
( Ps AI D 1 2. Q 1 [ pai n] N R S val ue × 3)
+( Ps AI D 1 2. Q 2 [fati g ue] N R S val ue × 2)
+( Ps AI D 1 2. Q 3 [ s ki n] N R S val ue × 2)
+( Ps AI D 1 2. Q 4 [ W or k a n d/ or leis ure acti vities] N R S val ue × 2)
+( Ps AI D 1 2. Q 5 [f u ncti o n] N R S val ue × 2)
+( Ps AI D 1 2. Q 6 [ disc o mf ort] N R S val ue x 2)
+( Ps AI D 1 2. Q 7 [slee p] N R S val ue × 2)
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 7 of 5 9
Dise ase acti vit y 
i n dic at ors
Defi niti o n/ C alc ul ati o n
+( Ps AI D 1 2. Q 8 [c o pi n g] N R S val ue × 1)
+( Ps AI D 1 2. Q 9 [a n xiet y ] N R S val ue × 1)
+( Ps AI D 1 2. Q 1 0 [e m barrass me nt] N R S val ue × 1)
+( Ps AI D 1 2. Q 1 1 [s ocial life] N R S val ue × 1)
+( Ps AI D 1 2. Q 1 2 [ de pressi o n] N R S val ue × 1)
T he t otal is di vi de d b y 2 0 f or t he fi nal sc ore.
Ps AI D 1 2 sc ore r a n ge: 0- 1 0
A b bre viati o ns: B S A = B o d y  S urface Ar ea, C R P = C-reacti ve pr otei n, D A P S A = Disease Acti vit y i n Ps oriatic 
Art hritis, H A Q -DI = Healt h Assess me nt Q uesti o n naire - Disa bilit y I n de x, L DI = Lee ds Dact ylitis I n de x, L EI = 
Lee ds E nt hesitis I n de x, M D A = mi ni m u m disease acti vit y, N R S = N u meric Rati n g Scale, P A S D A S = Ps oriatic 
Art hritis Disease Acti vit y Sc ore , P A SI = Ps oriasis Area a n d Se verit y I n de x , P R O = patie nt re p orte d o utc o me,
Ps AI D 1 2 = Ps oriatic Art hritis I m pact of Disease 1 2 Q uesti o ns , S P A R C C -EI = S p o n d yl oart hritis Researc h 
C o ns orti u m of Ca na da E nt hesitis I n de x, S F -3 6 = S h ort F or m 3 6, SJ C 6 6 = s w olle n j oi nt c o u nt ( 6 6), TJ C = 
te n der j oi nt c o u nt ( 6 8), V A S = Vis ual A nal o g ue Scale 
9. 4. D at a S o urces
N o visits or e xa mi nati o ns, la b orat or y tests, or pr oce d ures are ma n date d as part of t his st u d y,
data will be c ollecte d fr o m pa tie nt rec or ds a n d d uri n g r o uti ne cli nical care. I n vesti gat ors will
be re q ueste d t o pe rf or m c o m m o nl y use d Ps A disease assess me nts. Patie nts will be re q ueste d
t o c o m plete vali date d P R Os at eac h st u d y visit, w hic h will be c o m plete d i n pa per f or m i n
l ocal la n gua ge .
T his is a pr os pecti ve n o n- i nter ve nti o nal st u d y w here patie nt data will be e ntere d i nt o a n
electr o nic case re p ort f or m (e C R F) l ocate d o n a sec ure we b- base d electr o nic data e ntr y
( E D C) sys te m. T he use of a sta n dar dize d e C R F will e ns ure t hat dat a is ca pt ure d c o nsiste ntl y
acr oss sites. All sites will be trai ne d o n use of t he e C R F, a n d data e ntr y g ui deli nes will be
pr o vi de d. T he e C R F is t o be c o m plete d base d o n data t hat has bee n c ollecte d i n t he p atie nt
file. T he P R O c o m plete d b y patie nts will be e ntere d i nt o t he E D C s y ste m b y I QVI A.
9. 4. 1. P h ysic al Assess me nts 
P hysici a n Gl o b al Assess me nt
T he p h y sicia ns’ gl o bal o pi ni o n of t he s ki n a n d j oi nts rec or de d o n a 0 - 1 0 0 m m scale.
P atie nt Gl o b al Assess me nt
T he patie nts’ gl o bal o pi ni o n of t he s ki n a n d j oi nts rec or de d o n a 0 - 1 0 0 m m scale. 3 3
P atie nt P ai n Assess me nt
Patie nts will assess t he se verit y of t heir art hriti s pai n usi n g a 1 0 0 m m V A S b y placi n g a mar k 
o n t he scale bet wee n 0 ( n o pai n) a n d 1 0 0 ( m ost se vere pai n), w hic h c orres p o n ds t o t he
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 8 of 5 9
ma g nit u de of t heir pai n. T he mi ni m u m cli nicall y i m p orta nt differe nce of pai n V A S is
c o nsi dere d t o be 1 0 m m.
S w olle n J oi nt C o u nt ( S J C 6 6)
T he j oi nt assess or will als o assess 6 6 j oi nts f or s welli n g usi n g t he f oll o wi n g scale:
Prese nt/ A bse nt/ N ot D o ne/ N ot A p plica ble (f or artificial j oi nts). 3 8 Artificial j oi nts will n ot be
assesse d.
Te n der/ P ai nf ul J oi nt C o u nt ( T J C 6 8)
Si xt y -ei g ht ( 6 8) j oi nts will be assesse d t o deter mi ne t he n u m ber of j oi nts t hat are c o nsi dere d
te n der or pai nf ul. T he res p o nse t o press ure/ m oti o n o n eac h j oi nt wi ll be assesse d usi n g t he
f oll o wi n g scale: Prese nt/ A bse nt/ N ot D o ne/ N ot A p plica ble (f or artificial j oi nts).3 8 Artificial
j oi nts will n ot be assesse d.
Lee ds E nt hesitis I n de x ( L EI)
E val uate pai n /te n der ness o n press ure at 6 sites: ac hilles te n d o n i nserti o ns (ri g ht/left), me dial 
fe m oral c o n d yles (ri g ht/left), lateral e pico n d y les of t he h u mer us (ri g ht/left). Te n der ness o n
e xa mi nati o n is rec or de d as eit her 1 = prese nt or 0 = a bse nt f or eac h of t he 6 sites.3 9
Lee ds D actylitis I n de x ( L DI)
T he cli nicia n s q ueezes t he affecte d fi n gers wit h m o derate press ure a n d d oc u me nts t he 
patie nt’s res p o nse: 0 = n o te n der ness, 1 = te n der, 2 = te n der a n d wi nces, a n d 3 = te n der a n d
wit h dra ws. 4 0
B o dy S urf ace Are a ( B S A)
T he n u m ber of a patie nt’s ha n d areas affecte d, o n t he ass u m pti o n t hat o ne “ ha n d pri nt”
reflects a p pr o xi matel y 1 % of B S A.
9. 4. 2. P R Os
S h ort F or m 3 6 ( S F - 3 6)
T he S F -3 6 meas ures a patie nt’s f u ncti o nal healt h a n d well -bei n g base d o n 3 6 q uesti o ns a b o ut
p h y sical a n d me ntal healt h c o nce pts t hat are rele va nt acr oss a g e, disease, a n d treat me nt.
T hese q uesti o ns are c o m bi ne d i nt o gr o u pi n gs t o f or m 2 s u m mar y meas ures a n d 8 scales: t he
P h y sical C o m p o ne nt S u m mar y a n d its 4 scales ( p h ysical f u ncti o ni n g, r ole-p h y sical, b o dil y
pai n, a n d ge neral healt h); a n d t he Me ntal
C o m p o ne nt S u m mar y a n d its 4 scales ( vitalit y,
s ocial f u ncti o ni n g, r ole-e m oti o nal, a n d me ntal healt h). T he ra w sc ores are rec o de d t o a 1 0 0 -
p oi nt scale usi n g a sc ori n g ke y , a n d s u m mar y meas ure sc ores are calc ulate d. Hi g her sc ores
i n dicate a better Q o L.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 2 9 of 5 9
He alt h Assess m e nt Q uesti o n n aire - Dis a bility I n de x ( H A Q-DI)
T he H A Q -DI 4 1 assesses t he de gree of diffic ult y a patie nt has e x perie nce d d uri n g t he past
wee k i n 8 d o mai ns of dail y li vi n g acti vities: dressi n g a n d gr o o mi n g, arisi n g , eati n g, wal ki n g,
h y gie ne, reac h, gri p , a n d ot her acti vities. Eac h acti vit y cate g or y c o nsists of 2 - 3 ite ms. F or
eac h q uesti o n i n t he q uesti o n naire, t he le vel of diffic ult y is sc ore d fr o m 0 t o 3 wit h 0 
re prese nti n g “ n o diffic ult y,” 1 as “s o me diffic ult y ,” 2 as “ m uc h diffic ult y,” a n d 3 as “ u na ble 
t o d o”. A n y acti vit y t hat re q uires assista nce fr o m a n ot her i n di vi d ual or re q uires t he use of a n 
assisti ve de vice a dj usts t o a mi ni m u m sc ore of 2 t o re prese nt a m ore li mite d f u ncti o nal stat us. 
T he f or m s h o ul d t he n be c hec ke d b y t he site staff f or c o m plete ness.
Ps ori atic Art hritis I m p act of Dise ase 1 2 Q uesti o ns ( Ps AI D 1 2)
T he Ps AI D 1 2 is a Ps A s pecific q uesti o n naire desi g ne d t o meas ure i m pact of t he disease. It is 
c o m p ose d of 1 2 n u meric rati n g scales (ra n gi n g 0-1 0) , eac h assessi n g a differe nt d o mai n of 
healt h (pai n, fati g ue, s ki n pr o ble ms, w or k a n d/ or le is ure acti vities, f u ncti o nal ca pacit y ,
disc o mf ort, slee p dist ur ba nce, c o pi n g, a n xiet y , e m barrass me nt a n d/ or s ha me, s ocial 
partici pati o n, de pressi o n). T he f or m ula t o calc ul ate t he o verall sc ore uses wei g hts o n eac h 
d o mai n t o re bala nce t he c o ntri b uti o n of eac h d o mai n t o t he fi nal sc ore (Ta ble 3 ). T he wei g hts 
were deri ve d fr o m a s ur ve y of 4 7 4 patie nts wit h Ps A fr o m 1 3 c o u ntries .3 7
9. 4. 3. Pr o g n ostic F act ors
T he f oll o wi n g Ps A pr o g n ostic fact ors will be c o nsi dere d base d o n i nf or mati o n c ollecte d at
e nr oll me nt a n d ma y be use d t o stratif y res ults.

B MI  at e nr oll me nt ( < 1 8. 5, 1 8. 5 t o < 2 5, 2 5 t o < 3 0, ≥3 0).

Tr eat me nt li ne (t ofaciti ni b as m o n ot hera p y or c o m bi nati o n t hera p y wit h M T X).

D urati o n of s y m pt o ms of at least 6 wee ks pri or t o e nr oll me nt.

A b n or mal (a b o ve t he n or mal ra n ge) C R P or E S R.

T he f oll o wi n g will be deri ve d base d o n c o u nts of j oi nts affecte d b y art hritis at
e nr oll me nt, s pecifie d b y: s mall j oi nts, me di u m j oi nts, lar ge j oi nts, ha n d j oi nts:

Art hritis ≥3 j oi nt areas;

Art hritis of t he ha n d j oi nts;

S y m metric art hritis;

Art hritis of o nl y  1 me di u m -lar ge j oi nt;

Art hritis of 2 - 1 0 me di u m -lar ge j oi nts a n d/ or 1- 3 s mall j oi nts;
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 0 of 5 9

Art hritis of 4 - 1 0 s mall j oi nts wit h or wit h o ut i n v ol ve me nt of lar ge j oi nts;

Art hritis of > 1 0 j oi nts ( wit h at least o ne s mall j oi nt).
T he f oll o wi n g will b e re q ueste d fr o m ra di ol o gical re p orts at e nr oll me nt:

R he u mat oi d n o d ules;

U ne q ui v ocal ra di ol o gical er osi o n;

U ne q ui v ocal b o n y decalcificati o n l ocalize d t o t he j oi nts of t he ha n ds a n d wrists.
9. 5. St u d y S ize
Base d o n feasi bilit y t his n o n -i nter ve nti o nal st u d y will i ncl u de a p pr o xi matel y 2 0 0 patie nts .
F or a sa m ple size of 1 5 4 e val ua ble patie nts (ass u mi n g a 2 3 % dr o p -o ut rate), a 2-si de d 
9 5 % c o nfi de nce i nter val ( CI) f or a si n gle pr o p orti o n usi n g t he lar ge sa m ple n or mal 
a p pr o xi mati o n will e xte n d 0. 0 6 3 fr o m t he o bser ve d pr o p orti o n f or a n e x pecte d pr o p orti o n of 
0. 2.
T here are n o pla ns t o c o n d uct a n y h y p ot hesis testi n g or c o m paris o ns bet wee n gr o u ps
t heref ore n o f or mal sa m ple size calc ulati o n has bee n perf or me d.
9. 6. D at a M a n a ge me nt 
A data ma na ge me nt pla n ( D M P) will be create d bef ore t he start of data c ollecti o n a n d will
descri be all f u ncti o ns, pr ocesses, a n d s pecificati o ns f or data c ollecti o n, clea ni n g a n d
vali dati o n t o e ns ure t hat t he data are as clea n a n d as acc urate as p ossi ble w he n prese nte d f or
a nal ysis. Data c ollecti o n a n d vali dati o n pr oce d ures will be detaile d i n a p pr o priate o perati o nal
d oc u me nts. T he e C R Fs will i ncl u de pr o gra m ma ble e dit c hec ks t o o bt ai n i m me diate fee d bac k
if data are missi n g, o ut of ra n ge, ill o gical, or p ote ntiall y err o ne o us. C o nc urre nt ma n ual data
re vie w will be perf or me d base d o n para meters dictate d b y t he D M P. Q ueries will be
ge nerate d wit hi n t he E D C s yste m a n d f oll o we d u p f or res ol uti o n. C o nfir mati o n of t he data
c ollecte d is re q uire d b y t he p h y sicia n’s electr o nic si g nat ure.
All st u d y data will be rec or de d b y t he st u d y sites i n t he E D C s yste m I nter nati o nal B usi ness
Mac hi nes
Cli nical De vel o p me nt (I B M-C D) w hic h f ulfills all re q uire me nts of 2 1 C o de of
Fe deral Re g ulati o ns Part 1 1 a n d t h e ce ntral ser ver is bac ke d u p o nce a da y . Access t o t he
s yste m ta kes place via a sec ure we bsite. Access is o nl y gi ve n t o re gistere d users w h o l o g i n
wit h a u ni q ue user na me a n d pass w or d. De pe n di n g o n t heir f u ncti o n i n t he st u d y, i n di vi d ual
users are assi g ne d defi ne d access ri g hts. Access ri g hts t o t he E D C s yste m are m o nit ore d b y
a ut h orize d c o ntract researc h or ga nizati o n ( C R O) e m pl o y ees.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 1 of 5 9
9. 6. 1. C ase R e p ort F or ms ( C R Fs)
As use d i n t his p r ot oc ol, t he ter m C R F s h o ul d be u n derst o o d t o refer t o eit her a pa per f or m or 
a n electr o nic data rec or d or b ot h, de pe n di n g o n t he data c ollecti o n met h o d use d i n t his st u d y .
A C R F is re q uire d a n d s h o ul d be c o m plete d f or eac h i ncl u de d patie nt. T he c o m plete d
ori gi nal C R Fs are t he s ole pr o pert y of Pfizer a n d s h o ul d n ot be ma de a vaila ble i n a n y f or m t o 
t hir d parties, e xce pt f or a ut h orize d re prese ntati ves of Pfizer or a p pr o priate re g ulat or y 
a ut h orities, wit h o ut writte n per missi o n fr o m Pfizer. T he I n vesti gat or s ha ll e ns ure t hat t he 
C R Fs are sec urel y st ore d at t he st u d y  site i n a n e ncr ypte d ele ctr o nic f or m a n d will be 
pass w or d pr otecte d t o pre ve nt access b y u na ut h orize d t hir d parties.
T he I n vesti gat or has ulti mate res p o nsi bilit y  f or t he c ollecti o n a n d re p orti n g of all cli nical, 
safety, a n d la b orat or y data e ntere d o n t he C R Fs a n d a n y ot her data c ollecti o n f or ms (s o urce 
d oc u me nts) a n d e ns uri n g t hat t he y are acc urate, a ut he ntic/ ori gi nal, attri b uta ble, c o m plete, 
c o nsiste nt, le gi ble, ti mel y (c o nte m p ora ne o us), e n d uri n g, a nd a vaila ble w he n re q uire d. T he 
C R Fs m ust be si g ne d b y t he In vesti gat or or b y  a n aut h orize d staff me m ber t o attest t hat t he 
data c o ntai ne d o n t he C R Fs are tr ue. A n y c orrecti o ns t o e ntries ma de i n t he C R Fs or s o urce 
d oc u me nts m ust be date d, i nitiale d, a n d e x plai ne d (if necessar y ) a n d s h o ul d n ot o bsc ure t he 
ori gi nal e ntr y .
I n m ost cases the s o urce d oc u me nts are t he h os pital or t he p h y sicia n's c hart. In t hese cases, 
data c ollecte d o n t he C R Fs m ust matc h t h ose c harts.
I n s o me cases, t he C R F ma y als o ser ve as t he s o urce d oc u me nt. I n t hese cases, a d oc u me nt 
s h o ul d be a vaila ble at t he In vesti ga t or site a n d at Pfizer t hat clearly i de ntifies t h ose data t hat 
will be rec or de d o n t he C R F, a n d f or w hic h t he C R F will sta n d as t he s o urce d oc u me nt.
T he Me dical Dicti o nar y  f or Re g ulat or y Acti vities ( Me d D R A) sys te m or ga n class a n d 
preferre d ter m, will be us e d t o classif y (s yste m or ga n class a n d preferre d ter m) ver bati m
ter ms c ollecte d f or safet y e ve nts, me dical hist or y , a n d c o-m or bi dities. T he m ost u p date d
versi o n of Me d D R A
at t he ti me of c o n d ucti n g t he data a nal ysis will be use d. All c o nc o mita nt
me dicati o ns will be c o de d usi n g W orl d
Healt h Or ga nizati o n ( W H O) Dr u g Dicti o nar y versi o n
vali d at st u d y start.
9. 6. 2. Rec or d R ete nti o n
T o e na ble e val uati o ns a n d/ or i ns pecti o ns/a u dits fr o m re g ulat or y  a ut h orities or Pfizer, t he 
I n vesti gat or a grees t o kee p rec or ds, i ncl u di n g t he i de ntit y of all partici pati n g patie nts 
(s ufficie nt i nf or mati o n t o li n k rec or ds, e g, C R Fs a n d h os pital rec or ds), all ori gi nal si g ne d 
i nf or me d c o nse nt d oc u me nts, c o pies of all C R Fs, safet y re p orti n g f or ms, s o urce d oc u me nts, 
detaile d rec or ds of treat me nt di s p ositi o n, a n d a de q uate d oc u me ntati o n of rele va nt 
c orres p o n de nce (e g, letters, meeti n g mi n utes, a n d tele p h o ne call re p orts). T he rec or ds s h o ul d 
be retai ne d b y t he I n vesti ga t or acc or di n g t o l ocal re g ulati o ns or as s pecifie d i n t he cli nical 
st u d y a gree me nt, w hic he ver is l o n ger. T he I n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue 
t o be st ore d sec urely f or s o l o n g as t he y are retai ne d.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 2 of 5 9
If t he I n vesti gat or bec o mes u na ble f or an y  reas o n t o c o nti n ue t o retai n st u d y rec or ds f or t he 
re q uire d peri o d (e g, retire me nt, rel ocati o n), Pfizer s h o ul d be pr os pecti vely n otifie d. T he 
st u d y rec or ds m ust be tra nsferre d t o a desi g nee acce pta ble t o Pfizer, s uc h as a n ot her 
I n vesti gat or, a n ot her i nstit uti o n, or a n i n de pe n de nt t hir d part y arra n ge d b y Pfizer.
I n vesti gat or rec or ds m ust be ke pt f or a mi ni m u m of 1 5 years after c o m pleti o n or 
disc o nti n uati o n of t he st u d y or f or l o n ger if re q uire d b y  a p plica ble l ocal re g ulati o ns. 
T he I n vesti gat or m ust o btai n Pfizer's writte n per missi o n bef ore dis p osi n g of a n y rec or ds, 
e ve n if rete nti o n re quire me nts ha ve bee n met.
9. 7. D at a A n al ysis 
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of data c ollecte d i n t his st u d y will 
be d oc u me n te d i n a statistical a nalys is pla n ( S A P), w hic h will be date d, file d a n d mai ntai ne d 
b y  t he s p o ns or. T he S A P ma y m o dif y  t he pla ns o utli ne d i n t he pr ot oc ol; a n y maj or 
m o dificati o ns of pri mar y e n d p oi nt defi niti o ns or t heir a nal ys es w o ul d be reflecte d i n a 
pr o t oc ol a me n d me nt.
Ha n dli n g of missi n g data will be descri be d i n t he S A P, u nless ot her wise s pecifie d i n t he S A P
n o i m p utati o n will be perf or me d, a n d if c o nsi dere d necessar y se nsiti vit y a nal ysis c o ul d be 
perf or me d a n d will be descri be d i n t he S A P. Varia bles t o be use d i n t he a nal y ses will be 
deri ve d as descri be d i n Ta ble 3 .
Sta tistical A nal y sis S oft ware ( S A S® , Versi o n 9. 1 or a b o ve) will be use d f or all statistical
a nal yses descri be d.
9. 7. 1. A n al ysis P o p ul ati o ns
All e nr olle d set ( E N R) will c o ntai n all s u bjects w h o pr o vi de i nf or me d c o nse nt a n d met all 
eli gi bilit y criteria t o partici pate i n t his st u d y.
F ull a nal ys is set ( F A S) will c o ntai n all e nr olle d patie nts w h o ha ve recei ve d at least o ne d ose 
(i ncl u di n g partial d ose) of st u d y me dicati o n.
9. 7. 2. Effecti ve ness A n al yses
Descri pti ve statistics will be use d t o prese nt t he res ults of t his st u d y f or t he e n d p oi nts
d escri be d i n Secti o n 9. 1. 1 . C o nti n u o us varia bles will be prese nte d as t he n u m ber of
o bser vati o ns, mea n, me dia n, sta n dar d de viati o n, i n ter q uartile ra n ge, a n d ra n ge. Cate g orical
varia bles will be pr ese nte d as n u m ber of o bser vati o ns, fre q ue nc y , a n d perce nta ge, 2-si de d
9 5 % CI s will be i ncl u de d as a p pr o priate. Gra p hical s u m maries ma y als o be prese nte d.
Details of a n y statistical m o deli n g a n d s uita ble s u b -gr o u p a nal ys es, if a p plica ble, will be
defi ne d i n t he S A P.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 3 of 5 9
Pr o p orti o ns will be calc ulate d usi n g all patie nts wit h t he re q uire d meas ure me nts as t he
de n o mi nat or, a n d t he n u m ber of patie nts ac hie vi n g t he s pecifie d e n d p oi nt as t he n u merat or, 
as a p pr o priate.
C ha n ges fr o m baseli ne will use mi xe d effects m o dels f or re peat meas ures w he n a p pr o priate, 
wit h ti me p oi nt as a fi xe d effect, a n d baseli ne val ues i ncl u de d as c o variates. A d diti o nal 
p ote ntial c o nf o u n di n g varia bles will be e val uate d a n d i ncl u de d as c o variates w he n
a p pr o priate (e g, a ge, disease se verit y at e nr oll me nt, pr o g n ostic fact ors i n Secti o n 9. 4. 1 ).
9. 7. 3. S afet y A n al yses
Safet y data will be prese nte d i n ta b ular a n d/ or listi n g f or mat a n d s u m marize d desc ri pti vel y,
w here a p pr o priate. E ve nt c o u nt a n d A E fre q ue nc y will be re p orte d. N u m ber ( % of s u bjects)
wit h A Es, S A Es, a n d disc o nti n uati o ns d ue t o a n A E will be re p orte d.
9. 7. 4. I nteri m A n al ysis
N o i nteri m a nal ysis is pla n ne d as part of t his st u d y.
9. 8. Q u alit y C o ntr ol
D uri n g t he site i nitiati o n visit, t he m o nit or wil l pr o vi de trai ni n g o n t he c o n d uct of t he st u d y 
t o t he I nvesti gat or, c o -I nvesti gat or(s), a n d all site staff i n v ol ve d i n t he st u d y. I n or der t o
e ns ure t he i nte grit y of t he data , sites will be m o nit ore d. Site m onit ori n g will be perf or me d b y
I QVI A t o e xa mi ne co m plia nce wit h t he pr ot oc ol a n d a d here nce t o t he data c ollecti o n
pr oce d ures, t o assess t he acc u rac y a n d c o m plete ness of s u b mitte d cli nical data, a n d t o verif y
t hat rec or ds a n d d oc u me nts are bei n g pr o perl y mai ntai ne d f or t he d urati o n of t he st u d y. T he
m o nit or will perf or m s o urce data verificati o n b y re vie w of ori gi nal patie nt rec or ds.
T he m o nit or will cl ose o ut eac h site after t he last patie nt’s fi nal f oll o w -u p assess me nt is 
c o m plete d, all data ha ve bee n e ntere d a n d all o utsta n di n g m o nit ori n g iss ues ha ve bee n 
res ol ve d or a d dresse d. All m o nit ori n g pr oce d ures a n d fre q ue nc y of m o nit ori n g visits will be 
descri be d i n a m o nit ori n g pla n. M o nit or c o ntact details f or eac h partici pati n g site will be 
mai ntai ne d i n t he I n ve sti gat or Site File.
T he e C R Fs will i ncl u de pr o gr a m ma ble e dits t o o btai n i m me diate fee d bac k if data are 
missi n g, o ut of ra n ge, ill o gical or p ote ntiall y  err o ne o us. C o nc urre nt ma n ual data re vie w will 
be perf or me d base d o n para meters dictate d b y t he pla n. A d h oc q ueries will be ge nerate d 
wit hi n t he E D C s yst e m a n d f oll o we d u p f or res ol uti o n. All c orr ecti o ns of e ntries o n t he 
e C R Fs m ust be e x plai ne d (reas o n f or c ha n ge) a n d si g ne d off (electr o nic si g nat ures).
C orrecti o ns of e ntries are a ut o maticall y  rec or de d b y t he s ys te m (i ncl u di n g date of c ha n ge, 
user c ha n gi n g data, ol d a n d ne w val ue, reas o n f or c ha n ge).
Hi g h data q ualit y  sta n dar ds will be mai ntai ne d a n d pr ocesses a n d pr oce d ures utilize d t o 
re peate dl y e ns ure t hat t he data are as clea n a n d acc urate as p ossi ble w he n prese nte d f or
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 4 of 5 9
a nal ysis. Data q ualit y will be e n ha nce d t hr o u g h a series of pr o gra m me d data q ualit y  c hec ks
t hat a ut o maticall y detect o ut of ra n ge or a n o mal o us data .
9. 9. Li mit ati o ns of t he R ese arc h M et h o ds
O bser vati o nal st u dies are use d t o e val uate t he effecti v e ness a n d safet y of p har mac ol o gical
treat me nts in a real - w orl d setti n g.
Selecti o n bi as
Patie nts w h o e nr oll i n t he st u d y m a y differ fr o m patie nts w h o c h o ose n ot t o e nr oll, li ke wise
Ps A patie nts w h o are treate d wit h t ofaciti ni b ma y differ fr o m Ps A patie nts w h o are n ot. T he
eli gi bilit y criteria are n ot res tricti ve i n or der t o all o w e nr oll me nt of all Ps A patie nts i n dicate d
f or treat me nt wit h t ofaciti ni b. A scree ni n g l o g has bee n i ncl u de d t o c ollect de- i de ntifie d
i nf or mati o n o n patie nts w h o c h o ose n ot t o be e nr olle d, i ncl u di n g t heir reas o n f or n o n -
e nr oll me nt; t his will all o w f or a c o mparis o n t o deter mi ne if t he 2 p o p ulati o ns are differe nt.
I nf or m ati o n bi as
At t he I n vesti gat or le vel, i nf or mati o n bias ca n be miti gate d b y  caref ul C R F desi g n, e ns uri n g 
t hat all re q ueste d data is pr o perly c ollecte d. T he data c ollect e d fr o m me dical rec or ds re flect 
real-w orl d me dical practice a n d i n here ntl y i ncl u des missi n g data.
At a patie nt le vel, misclassificati o n of dr u g e x p os ure s h o ul d be c o nsi dere d. Me dical rec or ds 
pr o vi de detaile d i nf or mati o n o n prescri be d me dicati o n b ut ma y n ot c o ntai n i nf or mati o n o n 
t he act ual use of t he me dicati o n b y t he patie nt. It is als o p ossi ble t hat ot her c o nc o mita nt 
me dicati o ns will n ot be re p orte d b y t he patie nt a n d will be missi n g fr o m t he data base.
C o nf o u n di n g
Stratifie d a nal ys is a n d/ or a dj uste d a nal yses mi g ht be use d t o assess t he i m pact of p ote ntial 
c o nf o u n di n g varia bles. F urt her details will be gi ve n i n t he S A P. T h o u g h eff orts ha ve bee n 
ma de t o i de ntif y  a n d c ollect p ote ntial c o nf o u n di n g fact ors, it is p ossi ble t hat ot hers e xist.
Patie nts selecte d f or st u d y i ncl usi o n re prese nt a p o p ulati o n w h o are i nitiate d o n t ofaciti ni b as 
part of r o uti ne cli nical care. T he sa m ple of patie nts will be o btai ne d fr o m p h y sicia ns w h o are 
willi n g t o partici pate i n t he st u d y  a n d t here is a p ossi bilit y t hat certai n ty pes of patie nts will 
be selecte d t o be prescri be d t ofaciti ni b (selecti o n bias) a n d j oi n t he st u d y a n d t his c o ul d
p ote ntiall y ha ve a n i m pact o n ge neraliza bilit y of res ults (if t he ‘ty p e’ is e x pecte d t o i m pact
t he effecti ve ness). T heref ore, st u d y fi n di n gs ma y n ot be ge neraliza ble t o all Ps A patie nts.
9. 1 0. Ot her A s pects
N ot a p plica ble.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 5 of 5 9
1 0. P R O T E C TI O N O F H U M A N S U B J E C T S
1 0. 1. P atie nt Inf or m ati o n 
All parties will c o m pl y  wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical meas ures t o e ns ure t he pr otecti o n of patie nt pers o nal data.
S uc h meas ures will i ncl u de o mitti n g patie nt na mes or ot her directl y  i de ntifia ble data i n a ny 
re p orts, p u blicati o ns, or ot her discl os ures, e xce pt w here re q uire d b y  a p plica ble la ws.
T he pers o nal dat a will be store d at t he st u d y  site i n a n e ncr ypte d electr o nic f or m a n d will be 
pass w or d pr otecte d t o e ns ure t hat o nl y  a ut h orize d st u d y staff ha ve access. T he st u d y site will 
i m ple me nt a p pr o priate tec h nical a n d or ga nizatio nal meas ures t o e ns ure t hat t he per s o nal data 
ca n be rec o vere d i n t he e ve nt of disaster. I n t he e ve nt of a p ote ntial pers o nal data breac h, t he 
st u d y site s hall be res p o nsi ble f or deter mi ni n g w het her a pers o nal data breac h has i n fact 
occ urre d a n d if s o, p r o vi di n g breac h n otificati o ns as re quire d b y l a w.
T o pr otect t he ri g hts a n d free d o ms of nat ural pers o ns wit h re gar d t o t he pr ocessi n g of 
pers o nal data, w he n st u d y  data are c o m pile d f or tra nsfer t o Pfizer a n d ot her a ut h orize d 
parties, patie nt na mes will be re m o ve d a n d will be re place d by a si n gle, s pecif ic, n u merical 
c o de, base d o n a n u m beri n g s ys te m defi ne d b y Pfizer. All ot her i de ntifia ble data tra nsferre d 
t o Pfizer or ot her a ut h orize d parties will be i de ntifie d b y t his si n gle, patie nt-s pecific c o de.
T he I n vesti gat or site will mai ntai n a c o n fi de ntial list of patie nts w h o partici pate d i n t he 
st u d y, li n ki n g eac h patie nt’s n u merical c o de t o his or her act ual i de ntit y. I n case of data 
tra nsfer, Pfizer will mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr otecti o n of patie nts’
pers o nal data c o nsis te nt wit h t he cli nical st u d y a gree me nt a n d a p plica ble pri vac y la ws.
1 0. 2. P atie nt C o nse nt
T he i nf or me d c o nse nt d oc u me nts a n d a n y patie nt recr uit me nt materials m ust be i n
c o m plia nce wit h l ocal re g ulat or y re q uire me nts a n d le gal re q uire me nts, i ncl u di n g a p plica ble 
p ri vac y la ws.
T he i nf or me d c o nse nt d oc u me nts use d d uri n g t he i nf or me d c o nse nt pr ocess a n d a n y  patie nt 
recr uit me nt materials m ust be re vie we d a n d a p pr o ve d b y Pfizer, a p pr o ve d b y t he i nstit uti o nal 
re vie w b oar d (I R B)/i n de pe n de nt et hics c o m mittee (I E C) bef ore use, a n d a vaila ble f or 
i ns pecti o n.
T he I n vesti gat or m ust e ns ure t hat eac h st u d y  patie nt or his or her le gally acce pta ble 
re prese ntati ve is f ull y i nf or me d a b o ut t he nat ure a n d o bjecti ves of t he st u d y, t he s hari n g of 
data r elati n g t o t he st u d y a n d p ossi ble ris ks ass ociate d wit h partici pati o n, i ncl u di n g t he ris ks 
ass ociate d wit h t he pr ocessi n g of t he patie nt’s pers o nal data. T he I n vesti gat or f urt her m ust 
e ns ure t hat eac h st u d y patie nt or his or her le gall y acce pta ble re prese n tati ve is f ull y i nf or me d 
a b o ut his o r her ri g ht t o access a n d c orrect his or her pers o nal data a n d t o wit h dra w c o nse nt 
f or t he pr ocessi n g of his or her pers o nal data.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 6 of 5 9
W he ne ver c o nse nt is o btai ne d fr o m a patie nt’s le gall y  acce pta ble re prese ntati ve, t he patie nt’s 
asse nt (affir mati ve a gree me nt) m ust s u bse q ue ntl y be o btai ne d w he n t he patie nt has t he 
ca pacit y t o pr o vi de asse nt, as deter mi ne d b y t he I R B/IE C. I f t he I nvesti gat or deter mi nes t hat
a patie nt’s decisi o nal ca pacit y is s o li mite d t hat he or s he ca n n ot reas o na bl y be c o ns ulte d,
t he n, as per mitte d b y t he I RB/I E C a n d c o nsiste nt wit h l ocal re g ulat or y a n d le gal
re q uire me nts, t he patie nt’s asse nt ma y be wai ve d wit h s o urce d oc u me ntati o n of t he reas o n
asse nt was n ot o btai ne d. If t he st u d y patie nt d oes n ot pr o vi de his or her o w n c o nse nt, t he
s o urce d oc u me nts m ust rec or d w h y t he patie nt di d n ot pr o vi de c o nse nt (e g, mi n or,
decisi o nall y i m paire d a d ult), h o w t he I nvesti gat or deter mi ne d t hat t he pers o n si g ni n g t he
c o nse nt was t he patie nt’s le gall y acce pta ble re prese ntative, t he c o nse nt si g ner’ s relati o ns hi p
t o t he st ud y patie nt (e g, pare nt, s p o use), a n d t hat t he patie nt’s asse nt was o btai ne d or wai ve d.
If asse nt is o btai ne d ver ball y , it m ust be d oc u me nte d i n t he s o urce d oc u me nts.
T he I n vesti gat or, or a pers o n desi g nate d b y t he I n vesti gat or, will o btai n writte n i nf or me d
c o nse nt fr o m eac h patie nt or t he patie nt’s le gall y acce pta ble re prese ntati ve bef ore a n y st u d y-
s pecific acti vit y is perf or me d. T he I n vesti gat or will retai n t he ori gi nal of eac h patie nt's
si g ne d c o nse nt d oc u ment.
1 0. 3. P atie nt W it h dr a w al
Patie nts ma y wit h dra w fr o m t he st u d y at a n y ti me at t heir o w n re q uest, or t he y m a y be
wit h dra w n at a n y ti me at t he discreti o n of t he I n vesti gat or or s p o ns or f or safet y, be ha vi oral, 
or a d mi nistrati ve reas o ns. I n a n y  circ u msta nce, e very eff ort s h o ul d be ma de t o d oc u me nt 
patie nt o utc o me, if a p plica ble. T he I n vesti gat or w o ul d i n q uire a b o ut t he reas o n f or
wit h dra wal a n d f oll o w- u p wit h t he patie nt re gar di n g a n y u nres ol ve d A Es.
If t he patie nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nsent f or discl os ure of f ut ure 
i nf or mati o n, n o f urther e val uati o ns s h o ul d be perf or me d, a n d n o a d diti o nal data s h o ul d be 
collecte d . T he s p o ns or ma y retai n a n d c o nti n ue t o use a n y data c ollecte d bef ore s uc h
wit h dra wal of c o nse nt.
1 0. 4. I nstit uti o n al R e vie w B o ar d (I R B)/ I n de pe n de nt Et hics C o m mittee ( IE C)
It is t he res p o nsi bilit y of t he i n vesti gat or t o ha ve pr os pecti ve a p pr o val of t he st u d y pr ot oc ol, 
pr ot oc ol a me n d me nts, a n d i nf or me d c o nse nt f or ms, a n d ot her rele va nt d oc u me nts, (e g, 
recr uit me nt a d vertise me nts), if a p plica ble, fr o m t he IR B/I E C. All c orres p o n de nce wit h t he 
I RB/I E C s h o ul d be retai ne d b y  t he I n vesti gat or. C o pies of IR B/I E C a p pr o vals s h o ul d be 
f or war de d t o Pfizer. D ue t o t he o bser vati o nal nat ure of t his st u d y, I R B/I E C a p pr o val is n ot 
re q uire d i n De n mar k.
C o n siste nt wit h l ocal re g ulati o ns a n d pri or t o e nroll me nt of patie nts at a gi ve n site, t he st u d y  
pr ot oc ol will be s u b mi tte d t o get her wit h its ass ociate d d oc u me nts (e g, i nf or me d c o nse nt f or m 
[IC F]) t o t he res p o nsi ble I R B/I E C f or its re vie w. Patie nt e nr oll me nt will n ot start at a n y site 
bef ore t he Clie nt ha s o btai ne d writte n c o nfir mati o n of a fa v ora ble o pi ni o n/a p pr o val fr o m t he 
rele va nt ce ntral or l ocal I R B/I E C. T he I R B/I E C will be as ke d t o pr o vi de d oc u me ntati o n of 
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 7 of 5 9
t he date of t he meeti n g at w hic h t he fa v ora ble o pi ni o n/a p pr o val was gi ve n t hat clearl y 
i de ntifies t he st u d y, t he pr ot oc ol versi o n, a n d t he I C F versi o n re vie we d.
Be f ore i m ple me ntati o n of a n y s u bsta ntial c ha n ges t o t he pr ot oc ol, pr ot oc ol a me n d me nts will 
als o be s u b mitte d t o t he rele va nt I R B/ I E C i n a ma n ner c o nsiste nt wit h l ocal re g ulati o ns.
Perti ne n t safety i nf or mati o n will be s u b mitte d t o t he rele va nt I E Cs d uri n g t he c o urse of t he 
st u d y i n acc or da nce wit h l ocal re g ulati o ns a n d re q uire me nts. It is t he res p o nsi bilit y of t he
I nvesti gat or t o ha ve pr os pecti ve a p pr o val of t he st u d y pr ot oc ol, pr ot oc ol a me nd me nts, a n d
I CF, a n d ot her rele va nt d oc u me nts, if a p plica ble, fr o m t heir l ocal I RB/I E C a n d pr o vi de
d oc u me ntati o n of a p pr o val t o Pfizer. All c orres p o n de nce wit h t he I R B/I E C s h o ul d be
retai ne d i n t he I nvesti gat or file.
S h o ul d t he st u d y be ter mi nate d earl y f or a n y u na ntici pa te d reas o n, t he I nvesti gat or will be
res p o nsi ble f or i nf or mi n g t he I RB/I E C of t he e arl y ter mi nati o n.
1 0. 5. Et hic al C o n d uct of t he S t u d y
T he st u d y  will be c o n d ucte d i n acc or da nce wit h le gal a n d re g ulator y  re q uire me nts, as well as 
wit h scie ntific p u r p ose, val ue a n d ri g or a n d f oll o w ge nerally acce pte d researc h practices 
descri be d i n t he g ui deli nes of g o o d p har mac oe pi de mi ol o g y  practices ( G P P)4 2 iss ue d b y t he 
I nter nati o nal S ociet y f or P har mac oe pi de mi ol o g y  (IS P E), t he Declarati o n of Helsi n ki 4 3 a n d its 
a me n d me nts, a n d a n y a p plica ble nati o nal g ui deli nes.
Pri or t o t he e nr oll me nt of a n y patie nts i n t he st u d y, t he f oll o wi n g d oc u me nts m ust be
pr o vi de d b y t he site t o t he Clie nt ( or t heir desi g nee):

C o p y of t he I RB/I E C a p pr o val letter f or t he pr ot oc ol a n d i nf or me d c o nse nt (all
writte n i nf or mati o n pr o vi de d t o t he patie nt m ust be a p pr o ve d b y t he IR B/I E C);

C o p y of t he I RB/I E C -a p pr o ve d i nf or me d c o nse nt d oc u me nt t o be use d;

C o p y o f t he pr ot oc ol si g n-off pa ge si g ne d b y t he I nvesti gat or;

F ull y e xec ute d site a gree me nt.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 8 of 5 9
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S 
SI N G L E R E F E R E N C E S A F E T Y D O C U M E N T
T he Xelja nz (t ofaciti ni b) prescri bi n g i nf or mati o n will ser ve as t he si n gle refere nce safet y
d oc u me nt d uri n g t he c o urse of t he st u d y, w hic h will be use d b y Pfizer Safet y t o assess a n y 
safety e ve nts re p orte d t o Pfizer Safet y b y t he I n vesti gat or d uri n g t he c o urse of t his st u d y.
T he si n gle refere nce safet y  d oc u me nt s h o ul d be use d b y t he I n vesti gat or f or prescri bi n g 
p ur p oses a n d g ui da nce.
Patie nts e x perie nci n g e ve nts as liste d i n t he Xelja nz (t ofaciti ni b) prescri bi n g i nf or mati o n 
[ wit h partic ular atte nti o n pai d t o Secti o ns 4 ( C o ntrai n dicati o ns), 5 ( S pecial Warni n gs) a n d 
6 ( Preca uti o ns)] s h o ul d be m o nit ore d a n d if i n dicate d, treat me nt s h o ul d be wit h dra w n
acc or di n g t o t he pr o visi o n of t he res pecti ve prescri bi n g i nf or mati o n.
R E Q UI R E M E N T S
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or din g safety e ve nts o n t h e C R F a n d f or 
re p orti n g safet y e ve nts o n t he n o n-i nter ve nti o nal st u d y ( NIS) a d verse e ve nt m o nit ori n g 
( A E M) Re p ort F or m t o Pfizer Safety. T hese re q uire me nts are deli neate d f or t hree t y pes of 
e ve nts: ( 1) seri o us a d verse e ve nts ( S A Es); (2) n o n -seri o us A Es (as a p plica ble); a n d ( 3) 
scenari os i n v ol vi n g dr u g e x p os ure, i ncl u di n g e x p os ure d uri n g pre g na nc y , e x p os ure d uri n g 
breast fee di n g, me dicati o n err or, o ver d ose, mis use, e xtra vasati o n, lac k of efficac y , a nd 
occ u pati o nal e x p os ure .  T hese e ve nts are defi ne d i n t he secti o n “Defi niti o ns of safet y 
e ve nts.”
F or eac h A E, t he i n vesti gat or m ust p urs ue a n d o btai n i nf or mati o n a de q uate b ot h t o deter mi ne 
t he o utc o me of t he A E a n d t o assess w het her it meets t he criteria f or classificati o n as a S A E 
(refer t o secti o n "Seri o us A d verse E ve nts ” bel o w ).
S afet y e ve nt
Rec or de d o n t he C R F
Re p orte d o n t he NI S A E M Re p ort F or m t o 
Pfizer S afet y wit hi n 2 4 h o urs of a w are ness
S A E
All
All
N o n -seri o us A E
All

0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 3 9 of 5 9
Safet y e ve nts liste d i n t he ta ble a b o ve m ust be re p orte d t o Pfizer wit hi n 2 4 h o urs of 
a ware ness of t he e ve nt b y t he i n vesti gat or re g ar dless of w het her t he e ve nt is deter mi ne d 
b y t he i n vesti g at or t o be rel a te d t o Xelj a nz ® (t of aciti ni b). I n partic ular, if t he S A E is fatal 
or life -t hreate ni n g, n otificati o n t o Pfizer m ust be ma de i m me diatel y, irres pecti ve of t he e xte nt 
of a vaila ble e ve nt i nf or mati o n. T his ti mefra me als o a p plies t o a d diti o nal ne w (f oll o w- u p) 
i nfor mati o n o n pre vi o usl y f or war de d safet y e ve nt re p orts. I n t he rare sit uati o n t hat t he 
i n vesti gat or d oes n ot bec o me i m me diatel y a ware of t he occ urre nce of a safet y e ve nt, t he 
i n vesti gat or m ust re p ort t he e ve nt wit hi n 2 4 h o urs after lear ni n g of it a n d d oc u m ent t he ti me 
of his/ her first a ware ness of t he e ve nts.
F or safety e ve nts t hat are c o nsi dere d seri o us or t hat are i de ntifie d i n t he far-ri g ht c ol u m n of 
t he ta ble a b o ve t hat are re p orta ble t o Pfizer wit hi n 2 4 h o urs of a ware ness, t he i n vesti gat or is
o bli gate d t o p urs ue a n d t o pr o vi de a n y a d diti o nal i nf or mati o n t o Pfizer i n acc or da nce wit h 
t his 2 4-h o ur ti mefra me. I n a d diti o n, a n i n vesti gat or ma y be re q ueste d b y Pfizer t o o btai n 
s pecific f oll o w-u p i nf or mati o n i n a n e x pe dite d fas hi o n. T his i nf or mati o n is m ore det aile d 
t ha n t hat rec or de d o n t he C R F . I n ge neral, t his will i ncl u de a descri pti o n of t he A E i n 
s ufficie nt detail t o all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt 
deter mi nati o n of p ossi ble c a usalit y. A n y i nf or mati o n rele va nt t o t he e ve nt, s uc h as 
c o nc o mita nt me dicati o ns a n d ill nesses, m ust be pr o vi de d.  I n t he case of a patie nt deat h, a 
s u m mar y of a vaila ble a ut o ps y fi n di n gs m ust be s u b mitte d as s o o n as p ossi ble t o Pfizer or its 
desi g nate d re p rese ntati ve.
Re p orti n g peri o d 
F or eac h patie n t, t he safet y e ve nt re p orti n g peri o d be gi ns at t he ti me of  t he patie nt’s first 
d ose of Xelja nz ® (t ofaciti ni b) or t he ti me of t he patie nt’s i nf or me d c o nse nt if s/ he is bei n g 
treate d wit h Xelja nz ® (t ofaciti ni b) at st u d y start, a n d lasts t hr o u g h t he e n d of t he o bser vati o n
peri o d of t he st u d y, w hic h m ust i ncl u de at least 2 8 cale n dar da ys f oll o wi n g t he last 
a d mi nistrati o n of a dr u g u n der st u d y ; a re p ort m ust be s u b mitte d t o Pfizer Safety ( or its 
desi g nate d re prese n tati ve) f or a n y of t he ty pes of safet y e ve nts liste d i n t he ta ble a bo ve 
occ urri n g d uri n g t his peri o d. If a patie nt was a d mi nistere d a dr u g u n der st u d y o n t he last da y 
of t he o bser vati o n peri o d, t he n t he re p orti n g peri o d s h o ul d be e xte n de d f or 2 8 cale n dar d a ys 
Sce nari os i n v ol vi n g 
e x p os ure t o a dr u g u n der 
st u d y, i ncl u di n g 
e x p os ure d uri n g 
pre g na nc y, e x p os ure 
d uri n g breast fe edi n g, 
me dicati o n err or, 
o ver d ose, mis use, 
e xtra vasati o n, lac k of 
efficac y, a n d 
occ u pati o nal e x p os ure
All (re gar dless of w het her 
ass ociate d wi t h a n A E), 
e xce pt occ u p ati o n al 
e x p os ure
All (re gar dless of w het her ass ociate d wit h a n 
A E)
N ote: A n y ass ociate d A E is re p orte d t o get her 
wit h t he e x p os ure sce nari o.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 0 of 5 9
f oll o wi n g t he e n d of o bser vati o n. M ost oft en, t he date of i nf or m e d c o nse nt is t he sa me as t he 
date of e nr oll me nt. I n s o me sit uati o ns, t here ma y  be a la g bet wee n t he dates of i nf or me d 
c o nse nt a n d e nr oll me nt. I n t hese i nsta nces, if a patie nt pr o vi des i nf or me d c o nse nt b ut is ne ver 
e nr olle d i n t he st ud y (e. g., patie nt c ha n ges his/ her mi n d a b o ut partici pati o n), t he re p orti n g 
peri o d e n ds o n t he date of t he decisi o n t o n ot e nr oll t he patie nt.
If t he i n vesti gat or bec o mes a ware of a S A E occ urri n g at a n y ti me aft er c o m pleti o n of t he 
st u d y a n d s/ he c o nsi ders the S A E t o be relate d t o Xelja nz ® (t ofaciti ni b), t he S A E als o m ust 
be re p orte d t o Pfizer Safet y .
C a us alit y assess me nt
T he i n vesti gat or is re q uire d t o assess a n d rec or d t he ca usal relati o ns hi p . F or all A Es , 
s ufficie nt i nf or mati o n s h o ul d be o btai ne d b y t he in vesti gat or t o deter mi ne t he ca usalit y of 
eac h A E. F or A Es wit h a ca usal relati o ns hi p t o Xelja nz ® (t ofaciti ni b), f oll o w-u p b y  t he 
i n vesti gat or is re q uire d u ntil t he e ve nt a n d/or its se q uelae res ol ve or st a bilize at a le vel 
acce pta ble t o t he i n vesti gat or, a n d Pfizer c o nc urs wit h t hat assess me nt.   A n i n vesti gat or’s 
ca usalit y assess me nt is t he deter mi nati o n of w het her t here e xists a reas o na ble p ossi bilit y  t hat 
Xelja nz ® (t ofaciti ni b) ca use d or c o ntri b ute d t o a n A E. If t he i n vesti gat or’s fi nal 
deter mi nati o n of ca usalit y is “ u n k n o w n” a n d s/ he ca n n ot deter mi ne w het her Xelja nz ® 
(t ofaciti ni b) ca use d t he e ve nt, t he safet y e ve nt m ust be re p orte d wit hi n 2 4 h o urs.   
If t he i n vesti gat or ca n n ot deter mi ne t he eti ol o g y of the e v e nt b ut s/ he deter mi nes t hat 
Xelja nz ® (t ofaciti ni b) di d n ot ca use t he e ve nt, t his s h o ul d be clearl y  d oc u me nte d o n t he C R F
a n d t he NI S A E M Re p ort F or m . 
D E FI NI TI O N S O F S A F E T Y E V E N T S
A d verse e ve nts
A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt a d mi ni stere d a me dici nal pr o d uct . 
T he e ve nt nee d n ot necessaril y  ha ve a ca usal relati o ns hi p wit h t he pr o d uct treat me nt or 
usa ge . E xa m ples of A Es i ncl u de b ut are n ot li mite d t o: 
A b n or mal test fi n di n gs (see bel o w f or circ u msta nces i n w hic h a n a b n or mal test 
fi n di ng c o nstit utes a n A E);
Cli nicall y  si g nifica nt sig ns a n d s ym pt o ms ;
C ha n ges i n p h ys ical e xa mi nati o n fi n di n gs;
H y perse nsiti vit y ;
Pr o gressi o n/ w orse ni n g of u n derl yi n g disease ;
Lac k of efficac y; 
Dr u g a b use; 
Dr u g de pe n de nc y .
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 1 of 5 9
A d diti o nall y , f or me dici nal pr o d ucts , t he y ma y i ncl u de t he si g ns or sy m pt o ms res ult in g fr o m:
Dr u g o ver d ose ;
Dr u g wit h dra wal ;
Dr u g mis use;
Off -la bel use; 
Dr u g i nteracti o ns;
E xtra vasati o n ;
E x p os ure d uri n g p re g na nc y;
E x p os ure d uri n g breast fee di n g ;
Me dicati o n err or;
Occ u pati o nal e x p os ure.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 2 of 5 9
A b n o r mal test fi n di n gs
T he criteria f or deter mi ni n g w het her a n a b n or mal o bjecti ve test fi n di n g s h o ul d be re p orte d as 
a n A E are as f oll o ws: 
Test res ult is ass ociate d wit h acc o m pa n yi n g s y m pt o ms, a n d/ or
Test res ult re q uires a d diti o nal dia g n ost ic testi n g or me dical/s ur gical i nter ve nti o n, 
a n d/ or
Test res ult l ea ds t o a c ha n ge i n st u d y d osi n g or disc o nti n uati o n fr o m t he st u d y, 
si g nifica nt a d diti o nal c o nc o mita nt dr u g treat me nt, or ot her t hera py, a n d/ or
Test res ult is c o nsi dere d t o be a n A E b y  t he i nvesti gat or or s p o ns or.
Merel y re peati n g a n a b n or mal test, i n t he abse nce of a n y  of t he a b o ve c o n diti o ns, d oes n ot 
c o nstit ute a n A E . A ny a b n or mal test res ult t hat is deter mi ne d t o be a n err or d oes n ot re q uire 
re p orti n g as a n A E .
Seri o us a d verse e ve nts
A S A E is a n y u nt o war d me dical occ urre nce i n a patie nt a d mi nistere d a me dici nal or 
n utriti o nal pr o d uct (i ncl u di n g pe diatric f or m ulas) at a n y d ose t hat:
Res ults i n deat h;
Is life-t hreate ni n g;
Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n (see bel o w f or 
circu msta nces t hat d o n ot c o nstit ute A Es);
Res ults i n persiste nt or si g nifica nt disa bilit y /i nca pacit y (s u bsta ntial disr u pti o n of t he 
a bilit y t o c o n d uct n or mal life f u ncti o ns);
Res ults i n c o n ge nital a n o mal y / birt h defect.
Me dical a n d scie ntific j u d g me nt is e xerc ise d i n deter mi ni n g w het her a n e ve nt is a n i m po rta nt 
me dical e ve nt. A n i m p orta nt me dical e ve nt ma y  n ot be i m me diatel y life-t hreate ni n g a n d/ or 
res ult i n deat h or h os pitalizati o n. H o we ver, if it is deter mi ne d t hat t he e ve nt ma y je o par dize 
t he patie nt or ma y  re q uire i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he 
defi niti o n a b o ve , t he i m p orta nt me dical e ve nt s h o ul d be re p orte d as seri o us.
E xa m ples of s uc h e ve nts are i nte nsi ve treat me nt i n a n e mer ge nc y  r o om or at h o me f or 
aller gic br o nc h os pas m; bl o o d d y scrasias or c o n v ulsi o ns t hat d o n ot result i n h os pitalizati o n; 
or de vel o p me nt of dr u g de pe n de nc y  or dr u g a b use.
A d diti o nall y , a ny s us pecte d tra ns missi o n via a Pfizer pr o d uct of a n i nfecti o us a ge nt, 
pat h o ge nic or n o n -pat h o ge nic, is c o nsi dere d seri o us. T he e ve nt ma y  be s us pecte d fr o m 
cli nical s ym pt o ms or la b orat or y  fi n di n gs i n dicati n g a n i nfecti o n i n a patie nt e x p ose d t o a 
Pfizer pr o d uct. T he ter ms “s us pecte d tra ns missi o n” a n d “tra ns missi o n” are c o nsi dere d 
s yn o n y m o us. T hese cases are c o nsi dere d u ne x pe cte d a n d ha n dle d as seri o us e x pe dite d cases 
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 3 of 5 9
b y p har mac o vi gila nce ( P V ) pers o n nel. S uc h cases are als o c o nsi dere d f or re p orti n g as 
pr o d uct defects, if a p pr o priate.
H os pitalizati o n
H os pitalizati o n is defi ne d as a n y  i nitial a d missi o n (e ve n if less t ha n 2 4 h o urs) t o a h os pital or 
e q ui vale nt healt hcare faci lit y or a n y  pr ol o n gati o n t o a n e xisti n g a d missi o n. A d missi o n als o 
i ncl u des tra nsfer wit hi n t he h os pital t o a n ac ute/i nte nsi ve care u nit (e. g., fr o m t he ps yc hiatric 
wi n g t o a me dical fl o or, me dical fl o or t o a c o r o nar y care u nit, ne ur ol o gical fl o or t o a 
t u berc ul osis u nit).   A n e mer ge nc y  r o o m visit d oes n ot necessaril y c o nstit ute a h os pitalizati o n; 
h o we ver, a n e ve nt lea di n g t o a n e mer ge nc y r o o m visit s h o ul d be assesse d f or me dical 
i m p orta nce. 
H os pitalizati o n i n t h e a bse nce of a me dical A E is n ot i n itself a n A E a n d is n ot re p orta ble. 
F or e xa m ple, t he f oll o wi n g re p orts of h os pitalizati o n wit h o ut a me dical A E are n ot t o be 
re p orte d. 
S ocial a d missi o n (e. g., patie nt has n o place t o slee p).
A d mi nistrati ve a d missi o n (e. g., f or ye arl y e xa m).
O pti o nal a d missi o n n ot ass ociate d wit h a preci pitati n g me dical A E (e. g., f or electi ve 
c os metic s ur ger y).
H os pitalizati o n f or o bser vati o n wit h o ut a me dical A E .
A d missi o n f or treat me nt of a pre -e xisti n g c o n diti o n n ot ass ociate d wit h t he
de vel o p me nt of a ne w A E or wit h a w orse ni n g o f t he pre-e xisti n g c o n diti o n 
(e. g., f or w or k-u p of persiste nt pre -treat me nt la b a b n or malit y).
Sce n ari os necessit ati n g re p orti n g t o Pfizer S afet y wit hi n 2 4 h o urs
Sc e nari os i n v ol vi n g e x p os ure d uri n g pre g na nc y , ex p os ure d uri n g breastfee di n g, me dicati o n 
err or, o ver d ose, mis use, e xtra vasati o n , lac k of efficac y, a n d occ u pati o nal e x p os ure are 
descri be d bel o w.
E x p os ure d uri n g pre g na nc y
A n e x p os ure d uri n g pre g na nc y  (E D P ) occurs if:
1.
A fe male bec o mes, or is f o u n d t o be, pre g na nt eit her w hile recei vi n g or ha vi n g bee n 
ex p ose d t o (e.g. , e n vir o n me ntal) Xelja nz ® (t ofaciti ni b) or t he fe male bec o mes, or is 
f o u n d t o be, pre g na nt after disc o nti n ui n g a n d/or bei n g e x p ose d t o Xelja nz ®
(t ofaciti ni b) ( mater nal e x p os ure).
A n e xa m ple of e n vir o n me ntal e x p os ure w o ul d be a case i n v ol vi n g direct c o ntact wit h a 
Pfizer pr o d uct i n a pre g na nt w o ma n (e. g., a n urse re p orts t hat s he is pre g na nt a n d has bee n 
e x p ose d t o c he m ot hera pe utic pr o d uct s).
2. A male has bee n e x p ose d , eit her d ue t o treat me nt or e n v ir o n me ntal e x p os ure t o 
Xelja nz ® (t ofaciti ni b) p ri or t o or ar o u n d t he ti me of c o nce pti o n a n d/or is e x p ose d 
d uri n g t he part ner pre g na nc y  ( pater nal e x p os ure).
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 4 of 5 9
F or e x p os ure d uri n g pre g na nc y  i n st u dies of pre g na nt w o me n, data o n t he e x p os ure t o 
dr u g/ vacci ne of i nterest d uri n g pre g na nc y , are n ot re p orta ble u nless ass ociate d wit h seri o us 
or n o n -seri o us a d verse e ve nts. 
As a ge neral r ule, pr os pecti ve a n d retr os pecti v e e x p os ure d uri n g pre g na nc y  re p orts fr o m a n y 
s o urce are re p orta ble irres pecti ve of t he prese nce of an ass ociate d A E a n d t he pr oce d ures f or 
S A E re po rti n g s h o ul d be f oll o we d, wit h t he e xce pti o n of t h ose st u dies c o n d ucte d i n pre g na nt 
w o me n (as descri be d i n a b o ve), f or w hic h data o n t he e x p os ure are n ot re p orta ble u nless
ass ociate d wit h seri o us or n o n -seri o us a d verse e ve nts.
If a st u dy partici pa nt or s tu d y  partici pa nt ’s part ner bec o mes, or is f o u n d t o be, pre g na nt 
d uri n g t he st u d y partici pa nt ’s treat me nt wit h Xelja nz ® (t ofaciti ni b) t his i nf or mati o n m ust be 
s u b mitte d t o Pfizer, irres pecti ve of w het her a n A E h as occ urre d usi n g t he NI S A E M Re p ort 
F or m a n d t he E D P S u p ple me ntal F or m. 
I n a d diti o n, t he i nf or mati o n re gar di n g e n vir o n me ntal e x p os ure t o Xelja nz ® (t ofaciti ni b) i n a 
pre g na nt w o ma n (e . g., a patie nt re p orts t hat s he is pre g na nt a n d has bee n e x p ose d t o a 
c yt ot o xic pr o d uct b y i n halati o n or s pilla ge) m us t be s u b mitte d usi n g t he NI S A E M Re p ort 
F or m a n d t he E D P S u p ple me ntal F or m . T his m ust be d o ne irres pecti ve of w het her a n A E 
has occ urre d.  
Inf or mati o n s u b mitte d s h o ul d i ncl u de t he a ntici pate d date of deli ver y (see bel o w f or 
i nf or mati o n relate d t o ter mi nati o n of pre g na nc y).
F oll o w- u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y ; i n a d diti o n, f oll o w-
u p is c o n d ucte d t o o btai n i nf or mati o n o n E D P o utc o me f or all E D P re p orts wit h pre g na nc y
o utc o me u n k n o w n . A pre g na nc y  is f oll o we d u ntil c o m pleti o n or u ntil pre g na nc y  ter mi nati o n 
(e. g., i n d uce d a b orti o n) a n d Pfizer is n otifie d of t he o utc o me. T his i nf or mati o n is pr o vi de d as 
a f oll o w u p t o t he i nitial E D P re p ort. I n t he case of a li ve birt h, t he str uct ural i nte grity of t he 
ne o nate ca n be assesse d at t h e ti me of birt h. I n t he e ve nt of a ter mi nati o n, t he reas o n(s) f or 
ter mi nati o n s h o ul d be s pecifie d a n d, if cli nically p ossi ble, t he str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be assesse d by gr os s vis ual i ns pecti o n ( u nless pre-pr oce d ure test 
fi n di ng s are c o ncl usi ve f or a c o n ge nital a n o mal y a n d t he fi n di n gs are re p orte d) .
If t he o utc o me of t he pre g na nc y meets t he criteria f or a n S A E (e. g., ect o pic pre g na nc y, 
s p o nta ne o us a b orti o n, i ntra uteri ne fetal de mise, ne o natal deat h, or c o n ge nital a n o maly [i n a 
li ve b or n, a ter mi nate d fet us, a n i ntra uteri ne fetal de mise, or a ne o natal deat h]), t he 
pr oce d ures f or re p orti n g S A Es s h o ul d be f oll o we d.
A d diti o nal i nf or mati o n a b o ut pre g na nc y  o utc o mes t hat are re p orte d as S A Es f oll o ws: 
S p o nta ne o us a b orti o n i ncl u des misc arria ge a n d misse d a b ort i o n;
Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut re gar d 
t o ca usalit y, as S A Es. I n a d diti o n, i nfa nt deat hs after 1 m o nt h s h o ul d be re p orte d as 
S A Es w he n t he i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y relate d t o 
e x p os ure t o i n vesti gati o nal pr o d uct .
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 5 of 5 9
A d diti o nal i nf or mati o n re gar di n g t he e x p os ure d uri n g pre g na nc y  ma y be re q ueste d. F urt her 
f oll o w- u p of birt h o utc o mes will be ha n dle d o n a case-b y -case basis (e. g., f oll o w- u p o n 
preter m i n fa nts t o i de ntif y de vel op me ntal dela y s).  
I n t he case of pater nal e x p os ure, t he st u dy partici pa nt will be pr o vi de d wit h t he Pre g na nt 
Part ner Release of I nf or mati o n F or m t o deli ver t o his part ner. It m ust be d o c u me nte d t hat t he 
st u d y partici pa nt was gi ve n this letter t o pr o vi de t o his part ner .
E x p os ure d uri n g breastfee di n g
Sce nari os of e x p os ure d uri n g breastfee di n g m ust be re p orte d, i rres pecti ve of t he prese nce of 
a n ass ociate d AE .  A n e x p os ure d uri n g breastfee di n g re p ort is n ot create d w he n a Pfizer dr u g 
s pecifically a p pr o ve d f or use i n breastfee di n g w o me n (e. g., vita mi ns) is a d mi nistere d i n 
acc or d wit h a ut h orize d use.  H o we ver, if t h e i nfa nt e x perie nces a n A E ass ociate d wit h s uc h a 
dr u g’s a d mi n istrati o n, t he A E is re p orte d t o get her wit h t he e x p os ure d uri n g breastfee di n g.
Me dicati o n err or
A me dicati o n err or is a n y u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g, or a d mi nistrati o n 
of a me dici nal pr o d uct t hat ma y ca use or lea d t o i na p pr o priate me dicati o n use or patie nt har m 
w hile i n t he c o ntr ol of t he healt h care pr ofessi o nal, patie nt, or c o ns u mer.  S uc h e ve nts ma y 
be relate d t o pr ofessi o nal practice, healt h care pr o d ucts, pr oce d ures, a n d s yste ms i ncl u di n g: 
prescri bi n g; or der c o m m u nicati o n; pr o d u ct la beli n g, pac ka gi n g, a n d n o me nclat ure; 
c o m p o u n di n g; dis pe nsi n g; distri b uti o n; a d mi nistrati o n; e d ucati o n; m o nit ori n g; a n d use.  
Me dicati o n err ors i ncl u de:
Near misses, i n v ol vi n g or n ot i n v ol v i n g a patie nt directl y (e. g., i na d verte nt/err on e o us 
a d mi nistrati o n, w hic h is t he acci de ntal use of a pr o d uct o utsi de of la beli n g or 
prescri pti o n o n t he part of t he healt hcare pr o vi der or t he patie nt/c o ns u mer);
C o nf usi o n wit h re gar d t o i n ve nte d na me (e. g., tra de na me, bra n d na me).
T he i n vesti gat or m ust s u b mit t he f oll o wi n g me dicati o n err ors t o Pfizer, i rres pecti ve of t he 
prese nce of a n ass ociate d A E/ S A E :
Me dicati o n err ors i n v ol vi n g patie nt e x p os ure t o t he pr o d uct, w het her or n ot t he 
me dicati o n err or is acc o m pa nie d b y  a n A E.
Me dicati o n er r ors t hat d o n ot i n v ol ve a patie nt directl y (e. g., p ote ntial me dicati o n 
err ors or near misses ). W he n a me dicati o n err or d oes n ot i n v ol ve patie nt e x p os ure t o 
t he pr o d uct t he f oll o wi n g mi ni m u m criteria c o nstit ute a me dicati o n err or re p ort:

A n i de ntifia ble re p orter ;

A s us pec t pr o d uct ;

T he e ve nt me dicati o n err or.
O ver d ose, Mis use, E xtra vasati o n
Re p orts of o ver d ose, mis use, a n d e xtra vasati o n ass ociate d wit h t he use of a Pfizer pr o d uct are 
re p orte d t o Pfizer by t he i n vesti gat or , irres pecti ve of t he prese nce of a n ass ociate d A E/ S A E.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 6 of 5 9
Lac k of Efficac y
Re p orts of lac k of efficac y t o a Pfizer pr o d uct are re p orte d t o Pfizer b y  t he i n vesti gat or, 
irres pecti ve of t he prese nce of a n ass ociate d A E/ S A E or t he i n dicati o n f or use of t he Pfizer 
pr o d uct.
Occ u pati o nal E x p os ure
Re p orts of occ u pat io nal e x p os ure t o a Pfizer pr o d uct are re p orte d t o Pfizer b y  t he 
i n vesti gat or, irres pecti ve of t he prese nce of a n ass ociate d A E/ S A E .
1 2. P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S
I n t he e ve nt of a ny p r o hi biti o n or restricti o n i m p ose d (e. g., cli nical h ol d) b y a n a p plica ble 
c o m pete nt a ut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a ny ne w 
i nf or mati o n w hic h mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of a Pfizer 
pr o d uc t, Pfizer s h o ul d be i nf or me d i m me diatel y.  
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y  of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y patie nt s a gai nst a ny i m me diate hazar d, a n d of 
a n y seri o us breac hes of t his NI  st u d y pr otoc ol t hat t he i n vesti gat or bec o me s a ware of.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 7 of 5 9
1 3. R E F E R E N C E S
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0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
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[ Availa ble fr o m: htt ps:// w w w.e ma.e ur o pa.e u/e n/ d oc u me nts/ pr o d uct -
i nf or mati o n/ xelja nz-e par-pr o d uct -i nf or mati o n _e n. p df.
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i nfla m mat or y acti vit y a n d ne utr o p hil re d ucti o ns me diate d b y t he J A K 1/J A K 3 i n hi bit or,
C P -6 9 0, 5 5 0, i n rat a dj u va nt -i n d uce d art hritis. J o ur nal of i nfla m mati o n. 2 0 1 0; 7( 1): 4 1.
2 2.
M urra y
PJ. T he J A K-S T A T si g nali n g pat h wa y : i n p ut a n d o ut p ut i nte grati o n. T he
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O' S ulli va n L A, Li o n g ue C, Le wis R S, Ste p he ns o n S E, War d A C. C y t o ki ne rece pt or
si g nali n g t hr o u g h t he Ja k– Stat – S ocs pat h wa y i n disease. M olec ular i m m u n ol o g y.
2 0 0 7; 4 4( 1 0): 2 4 9 7 -5 0 6.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 4 9 of 5 9
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researc h & t hera py. 2 0 0 8; 1 0( 1): R 1 4.
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Mease
P, Hall S, Fitz Geral d O, va n der Heij de D, Mer ola J F, A vila -Za pata F, et al.
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of Me dici ne. 2 0 1 7; 3 7 7( 1 6): 1 5 3 7 -5 0.
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Gla d ma n D, Ri g b y W, Aze ve d o V F,
B e hre ns F, Bla nc o R, Kasz u ba A, et al. T ofaciti n i b
f or ps oriatic art hritis i n patie nts wit h a n i na de q uate res p o nse t o T N F i n hi bit ors. Ne w 
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2 9.
Zi n k A, Stra n gfel d A, Sc h nei der M, Herzer P, Hierse F, St o y a n o va‐ Sc holz M, et al.
Effecti ve ness of t u m or necr osis fact or i n hi bit ors i n r he u mat oi d art hritis i n a n 
o bser vati o nal c o h ort st u d y: c o m paris o n of patie nts acc or di n g t o t heir eli gi bilit y f or 
maj or ra n d o mize d cli nical trials. Art hritis & R he u matis m: Official J o ur nal of t he
A merica n C olle ge of R he u mat ol o g y . 2 0 0 6; 5 4( 1 1): 3 3 9 9 -4 0 7.
3 0.
va n der Heij de D, S har p J, Wasse n ber g
S, Gla d ma n D D. Ps oriatic art hritis i ma gi n g: a 
re vie w of sc ori n g met h o ds. A n nals of t he R he u matic Diseases. 2 0 0 5; 6 4(s u p pl2):ii 6 1 -ii 4.
3 1.
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al. T he de vel o p me nt of ca n di date c o m p osite disease acti vit y a n d res p o n der i n dices f or 
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9 1.
3 2.
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0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 5 0 of 5 9
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L u bra n o E, Perr otta F, Ka va na u g h A. A n o ver vie w of l o w disease acti vit y a n d 
re missi o n i n ps oriatic art hritis. Cli n E x p R he u mat ol. 2 0 1 5; 3 3( 5 S u p pl 9 3): S 5 1 -S 4.
3 6.
Ma ks y m o w y c h W P, Mall o n C, M orr o w S, S h oja nia K, Olsz y ns ki W P,
W o n g R L , et al.
De vel o p me nt a n d vali dati o n of t he s p o n d yl oart hritis researc h c o ns orti u m of Ca na da
( S P A R C C) e nt hesitis i n de x. A n nals of t he R he u matic Diseases. 2 0 0 9; 6 8( 6): 9 4 8 -5 3.
3 7.
G ossec L, de Wit
M,
Kiltz U, Bra u n J , Kal y o nc u U, Scri v o R, et al. A patie nt -deri ve d
a n d patie nt -re p orte d o utc o me meas ure f or assessi n g ps oriatic art hritis: ela b orati o n a n d
preli mi nar y vali dati o n of t he Ps oriatic Art hritis I mpact of Disease ( Ps AI D)
q uesti o n naire, a 1 3-c o u ntr y E U L A R i nitiati ve. A n nals of t he r he u matic diseases.
2 0 1 4; 7 3( 6): 1 0 1 2 - 9.
3 8.
Mease PJ. Meas ures of ps oriatic art hritis: Te n der a n d S w olle n J oi nt Assess me nt, 
Ps oriasis Area a n d Se verit y I n de x ( P A SI), Nail Ps oriasis Se verit y I n de x ( N A P SI),
M o difie d Nail Ps oriasis Se verit y  I n de x ( m N A P SI), Ma n der/ Ne wcastle E nt hesitis I nde x
( M EI), Lee ds E nt hesitis I n de x ( LEI ), S p o n d y l oart hritis Researc h C o ns orti u m of Ca na da
( S P A R C C), Maastric ht A n k y l osi n g S p o n d y litis E nt hesis Sc ore ( M A S E S), Lee ds
Dact y litis I nde x ( L DI), Patie nt Gl o bal f or Ps oriatic Art hrit is, Der mat ol o g y Li fe Q uali t y
I n de x ( D L QI), Ps oriatic Art hritis Q ualit y of Life ( Ps A Q O L), F u ncti o nal Assess me nt of 
C hr o nic Ill ness T hera p y – Fati g ue ( F A CI T -F), Ps oriatic Art hritis Res p o nse Criteria
( Ps A R C), Ps oriatic Art hritis J oi nt Acti vit y I nde x ( Ps AJ AI), Disease Acti vit y i n
Ps oriatic Art hritis ( D A P S A), a n d C o m p osite Ps oriatic Disease Acti vit y I nde x ( C P D AI).
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3 9.
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Art hritis Care & Researc h. 2 0 0 8; 5 9( 5): 6 8 6 -9 1.
4 0.
Helli well P S, Firt h J, I bra hi m G H, Mels o m R D, S ha h I, T ur ner D E. De vel o p me nt of a n
assess me nt t o ol f or dact ylitis i n patie nts wit h ps oria tic art hritis. T he J o ur nal of
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4 1.
Fries J F. T he di me nsi o ns of healt h o utc o mes: t he healt h assess me nt q uesti o n naire, 
disa bilit y a n d pai n scales. j R he u mat ol. 1 9 8 2; 9: 7 8 9 -9 3.
4 2.
P u blic P olic y C o m mittee I So P. G ui deli nes f or g o o d p har mac oe pi de mi ol o g y pr actice
( G P P). P har mac oe pi de mi ol o g y a n d Dr u g Safet y . 2 0 1 6; 2 5( 1): 2 -1 0.
4 3.
W orl d Me dical Ass ociati o n Declarati o n of Helsi n ki: et hical pri nci ples f or me dical 
researc h i n v ol vi n g h u ma n s u bjects. J ama. 2 0 1 3; 3 1 0( 2 0): 2 1 9 1 - 4.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)

T ofaciti ni b (C P -6 9 0, 5 5 0)
A 3 9 2 1 3 3 2 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 2. 0 , 1 4 Fe br uar y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 1 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Pri m ary D at a C ollecti o n St u dy 0 1-
J u n -2 0 2 2
Pa ge 5 1 of 5 9
1 4. LI S T O F T A B L E S 
Ta ble 1 . Sc he d ule of Acti vities
Ta ble 2 . Assess me nts Re q uire d f or Deri va ti o n of St u d y E n d p oi nts
Ta ble 3 . Calc ulati o n of Disease Acti vit y  I n dicat ors
1 5. LI S T O F FI G U R E S
Fi g ure 1 .
St u d y  Desi g n
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S
C o ntact details a n d t he list of all I nvesti gat ors a vaila ble u p o n re q uest.
A N N E X 2 . A D DI TI O N A L I N F O R M ATI O N
N ot a p plica ble.
0 9 0 1 7 7 e 1 9 d 3 1 c a 1 c\ A p pr o v e d\ A p pr o v e d O n: 2 4- M a y- 2 0 2 3 1 3: 5 3 ( G M T)