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Clinical Trial Results:
A Phase 3b/4, Multi-Center, Double-Blind, Randomized, Parallel Group Study of Tofacitinib (CP-690,550) in Subjects With Ulcerative Colitis in Stable Remission

Summary
EudraCT number	2017-002274-39
Trial protocol	SK CZ BE HU NL GB AT ES IT
Global end of trial date	18 Mar 2022

Results information
Results version number	v1(current)
This version publication date	10 Mar 2023
First version publication date	10 Mar 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

A3921288

ISRCTN number

US NCT number

NCT03281304

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Aug 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Mar 2022

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy and safety of tofacitinib in subjects in stable remission on 10 milligram (mg) twice daily (BID) who decrease the dose to and remain on 5 mg BID (“5 mg BID dose group”) compared to subjects remaining on 10 mg BID.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 9

Country: Number of subjects enrolled

Canada: 3

Country: Number of subjects enrolled

Czechia: 3

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Hungary: 7

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Japan: 16

Country: Number of subjects enrolled

Korea, Republic of: 12

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

New Zealand: 4

Country: Number of subjects enrolled

Poland: 5

Country: Number of subjects enrolled

Russian Federation: 3

Country: Number of subjects enrolled

Serbia: 9

Country: Number of subjects enrolled

Slovakia: 13

Country: Number of subjects enrolled

South Africa: 9

Country: Number of subjects enrolled

Spain: 5

Country: Number of subjects enrolled

Ukraine: 12

Country: Number of subjects enrolled

United Kingdom: 1

Country: Number of subjects enrolled

United States: 23

Worldwide total number of subjects

140

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

122

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study enrolled subjects from A3921139(NCT01470612) who were on tofacitinib 10 mg BID for at least 2 consecutive years, who were in stable remission for at least 6 months prior to baseline of A3921288, not receiving any corticosteroid treatment to treat their ulcerative colitis (UC) for at least 4 weeks prior to enrollment.

Screening details

The Baseline visit of this study was the last visit in study A3921139. All procedures done at the last visit in A3921139 for subjects enrolled into this study were used as the Baseline data for this study. The study was conducted in 18 countries from 16-Nov-2017 to 18-Mar-2022.

Period 1 title

Treatment Phase (up to 42 Months)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Tofacitinib 5 mg BID

Arm description

Subjects received tofacitinib 5 mg tablet with one tablet of matching placebo, orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tofacitinib 5 mg tablet orally BID.

Tofacitinib 10 mg BID

Arm description

Subjects received tofacitinib 10 mg tablets (2 tablets of 5 mg), orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tofacitinib 10 mg tablet orally BID.

Number of subjects in period 1	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Started	70	70
Completed	36	27
Not completed	34	43
Adverse event, not serious	3	1
Consent withdrawn by subject	5	12
Death	-	1
Pregnancy	1	-
Study terminated by sponsor	15	16
Adverse event, serious non-fatal	7	8
Unspecified	-	2
Adverse event, serious (fatality unknown)	-	1
Lack of efficacy	3	2

Period 2 title

Follow-up Phase (up to 4 Weeks)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Tofacitinib 5 mg BID

Arm description

Subjects received tofacitinib 5 mg tablet with one tablet of matching placebo, orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tofacitinib 5 mg tablet orally BID.

Tofacitinib 10 mg BID

Arm description

Subjects received tofacitinib 10 mg tablets (2 tablets of 5 mg), orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received tofacitinib 10 mg tablet orally BID.

Number of subjects in period 2	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Started	63	57
Completed	61	56
Not completed	2	1
Unspecified	2	1

Baseline characteristics

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Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects received tofacitinib 5 mg tablet with one tablet of matching placebo, orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects received tofacitinib 10 mg tablets (2 tablets of 5 mg), orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Reporting group values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Total
Number of subjects	70	70	140
Age Categorical
Units: subjects
<=18 years	0	0	0
Between 18 and 65 years	59	63	122
>=65 years	11	7	18
Age continuous
Units: years
arithmetic mean (standard deviation)	47.81 ( 14.15 )	47.81 ( 13.55 )	-
Sex: Female, Male
Units: subjects
Female	26	22	48
Male	44	48	92
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	15	14	29
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	3	0	3
White	50	50	100
More than one race	0	1	1
Unknown or Not Reported	2	5	7
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	1	2
Not Hispanic or Latino	68	67	135
Unknown or Not Reported	1	2	3

End points

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Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects received tofacitinib 5 mg tablet with one tablet of matching placebo, orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects received tofacitinib 10 mg tablets (2 tablets of 5 mg), orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects received tofacitinib 5 mg tablet with one tablet of matching placebo, orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects received tofacitinib 10 mg tablets (2 tablets of 5 mg), orally, BID up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Primary: Number of Subjects With Remission Based on Modified Mayo Score at Month 6

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End point title

Number of Subjects With Remission Based on Modified Mayo Score at Month 6

End point description

Remission as per modified mayo score was defined as an endoscopic subscore of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding subscore of 0 at Month 6. Modified mayo score consisted of 3 components: stool frequency subscore, rectal bleeding subscore and endoscopic subscore: higher scores for each score = more severe disease. These scores were summed up to give a total modified mayo score range of 0 to 9; where higher scores indicating more severe disease. Full analysis set (FAS) included all subjects who were randomised and received at least 1 dose of investigational product (IP).

End point type

Primary

End point timeframe

Month 6

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects	54	63

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

12.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

Secondary: Time to Loss of Remission Based on Modified Mayo Score Using Kaplan-Meier Method

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End point title

Time to Loss of Remission Based on Modified Mayo Score Using Kaplan-Meier Method

End point description

Time to loss of remission(flare):time from first drug administration until time of meeting loss of remission criteria based on modified mayo score(MMS). Loss of remission: meeting >=1 criteria: increase from Baseline in rectal bleeding subscore by >=1 point, increase in endoscopic subscore by >=1 point; increase from Baseline in rectal bleeding subscore by >=2 points, endoscopic subscore >0; increase in stool frequency subscore by >=2 points, increase in endoscopic subscore by >=1point; increase in endoscopic subscore by >=2points. MMS included 3 components: stool frequency, rectal bleeding and endoscopic subscores, each subscore graded from 0 to 3 with higher scores for each score=more severe disease. All scores summed up to give total modified mayo score range from 0 to 9; higher scores=more severe disease. FAS: all subjects who were randomised and received at least 1 dose of IP. 999=Median was not estimated due to insufficient number of subjects with event.

End point type

Secondary

End point timeframe

Up to Month 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Days
median (full range (min-max))	999 (29 to 1268)	1270 (28 to 1270)

No statistical analyses for this end point

Secondary: Number of Subjects With Remission Based on Modified Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

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End point title

Number of Subjects With Remission Based on Modified Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point description

Remission as per modified partial mayo score was defined as stool frequency subscore of 0 or 1, and rectal bleeding sub score of 0 at the specified time points. Modified partial mayo scores consisted of 2 components: stool frequency and rectal bleeding: each subscore graded from 0 to 3 with higher scores for each score = more severe disease. These scores were summed up to give a total modified partial mayo score range of 0 to 6; where higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
Month 1	62	64
Month 3	57	65
Month 6	57	67
Month 9	52	66
Month 12	50	61
Month 15	48	58
Month 18	45	55
Month 21	46	51
Month 24	47	51
Month 27	43	49
Month 30	44	46
Month 33	42	43
Month 36	42	44
Month 39	40	37
Month 42	26	29

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 1: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

13.4

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 3: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

11.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

22.8

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 6: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

14.3

Confidence interval

level

95%

sides

2-sided

lower limit

2.9

upper limit

25.2

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 9: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

31.8

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 12: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

28.7

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 18: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

14.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

28.5

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 15: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

14.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

27.9

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 21: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

7.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

21.9

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 24: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

5.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

20.4

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 27: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

8.6

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

23.6

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 30: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-12.8

upper limit

18.3

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 33: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

17.2

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 36: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

18.5

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 39: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

-4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-20.2

upper limit

11.9

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 42: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

19.9

Secondary: Number of Subjects With Remission Based on Total Mayo Score at Months 6, 18, 30 and 42

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End point title

Number of Subjects With Remission Based on Total Mayo Score at Months 6, 18, 30 and 42

End point description

Remission as per total mayo score was defined by a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and physician global assessment (PGA), each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: subject’s recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Months 6, 18, 30 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
Month 6	53	61
Month 18	33	47
Month 30	35	44
Month 42	22	24

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 6: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

11.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

24.1

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 18: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.6

upper limit

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 30: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

12.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

28.3

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 42: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-12.5

upper limit

Secondary: Number of Subjects With Remission Based on Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

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End point title

Number of Subjects With Remission Based on Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point description

Remission as per partial mayo score was defined as partial mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: subject’s recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score ranges from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease. Full analysis set included all subjects who were randomised and received at least 1 dose of investigational product.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
Month 1	62	64
Month 3	57	65
Month 6	56	66
Month 9	52	66
Month 12	50	61
Month 15	48	58
Month 18	44	55
Month 21	46	50
Month 24	46	51
Month 27	42	49
Month 30	43	46
Month 33	42	43
Month 36	42	44
Month 39	39	37
Month 42	26	28

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 3: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

11.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

22.8

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 1: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

13.4

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 6: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

14.3

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

25.6

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 9: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

31.8

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 12: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

28.7

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 18: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

29.9

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 15: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

14.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

27.9

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 21: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

5.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.5

upper limit

20.6

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 24: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

7.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

21.9

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 27: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

25.1

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 30: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.4

upper limit

19.7

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 33: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

17.2

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 36: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

18.5

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 39: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

-2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-18.8

upper limit

13.3

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 42: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

18.5

Secondary: Number of Subjects With Remission Based on Modified Mayo Score at Months 18, 30 and 42

Top of page

End point title

Number of Subjects With Remission Based on Modified Mayo Score at Months 18, 30 and 42

End point description

Remission as per modified mayo score was defined as an endoscopic subscore of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding subscore of 0. Modified mayo score consisted of 3 components: stool frequency subscore, rectal bleeding subscore and endoscopic subscore: higher scores for each score = more severe disease. These scores were summed up to give a total modified mayo score range of 0 to 9; where higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Months 18, 30 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
Month 18	37	48
Month 30	35	44
Month 42	23	24

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 18: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

30.8

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 42: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

16.7

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 30: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

12.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

28.3

Secondary: Change From Baseline in Modified Mayo Score at Month 6

Top of page

End point title

Change From Baseline in Modified Mayo Score at Month 6

End point description

Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, ‘Number of Subjects Analysed’ =subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Month 6

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	67	68
Units: Units on a scale
least squares mean (standard error)	0.6 ( 0.2 )	0.3 ( 0.2 )

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.1

Secondary: Change From Baseline in Modified Mayo Score at Months 18, 30 and 42

Top of page

End point title

Change From Baseline in Modified Mayo Score at Months 18, 30 and 42

End point description

Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease. FAS included all subjects who were randomised and received at least 1 dose of investigational product. Here, ‘Number of Subjects Analysed’ =subjects evaluable for this endpoint and n= number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 18, 30 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	48	57
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Month 18 (n= 48, 57)	0.5 ( 1.3 )	0.3 ( 1.5 )
Change at Month 30 (n= 44, 45)	0.3 ( 1.2 )	0.1 ( 0.9 )
Change at Month 42 (n= 40, 34)	0.3 ( 0.9 )	0.2 ( 1.1 )

No statistical analyses for this end point

Secondary: Change From Baseline in Modified Partial Mayo Score at Months 1, 3 and 6

Top of page

End point title

Change From Baseline in Modified Partial Mayo Score at Months 1, 3 and 6

End point description

Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total modified partial mayo score range from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint and n = number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 1, 3 and 6

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	67	69
Units: Units on a scale
least squares mean (standard error)
Change at Month 1 (n= 67, 66)	0.1 ( 0.1 )	0.2 ( 0.1 )
Change at Month 3 (n= 64, 68)	0.2 ( 0.1 )	0.1 ( 0.1 )
Change at Month 6 (n= 60, 69)	0.1 ( 0.1 )	0.2 ( 0.1 )

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Least Squares (LS) Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.3

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.2

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.3

Secondary: Change From Baseline in Modified Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Top of page

End point title

Change From Baseline in Modified Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point description

Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total modified partial mayo score range from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, ‘Number of Subjects Analysed’ =subjects evaluable for this endpoint and n= number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	53	67
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Month 9 (n= 53, 67)	0.1 ( 0.7 )	0.1 ( 0.6 )
Change at Month 12 (n= 51, 63)	0.1 ( 0.5 )	0.1 ( 0.7 )
Change at Month 15 (n= 51, 57)	0.2 ( 0.8 )	0.1 ( 0.6 )
Change at Month 18 (n= 47, 56)	0.1 ( 0.6 )	0.1 ( 0.8 )
Change at Month 21 (n= 48, 54)	0.1 ( 0.5 )	0.2 ( 1.1 )
Change at Month 24 (n= 47, 50)	0.0 ( 0.5 )	0.0 ( 0.6 )
Change at Month 27 (n= 45, 48)	0.1 ( 0.5 )	0.1 ( 0.7 )
Change at Month 30 (n= 45, 45)	0.1 ( 0.7 )	0.0 ( 0.6 )
Change at Month 33 (n= 42, 41)	0.0 ( 0.4 )	0.2 ( 0.7 )
Change at Month 36 (n= 43, 41)	0.0 ( 0.5 )	0.0 ( 0.5 )
Change at Month 39 (n= 40, 34)	0.0 ( 0.5 )	0.0 ( 0.5 )
Change at Month 42 (n= 26, 26)	0.1 ( 0.4 )	0.1 ( 0.7 )

No statistical analyses for this end point

Secondary: Change From Baseline in Total Mayo Score at Month 6

Top of page

End point title

Change From Baseline in Total Mayo Score at Month 6

End point description

Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease. Full analysis set included all subjects who were randomised and received at least 1 dose of investigational product. Here, ‘Number of Subjects Analysed’ =subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Month 6

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	67	68
Units: Units on a scale
least squares mean (standard error)	0.9 ( 0.2 )	0.4 ( 0.3 )

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.1

Secondary: Change From Baseline in Total Mayo Score at Months 18, 30 and 42

Top of page

End point title

Change From Baseline in Total Mayo Score at Months 18, 30 and 42

End point description

Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: subject’s recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, ‘Number of Subjects Analysed’ =subjects evaluable for this endpoint and n = number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 18, 30 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	48	57
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Month 18 (n= 48, 57)	0.7 ( 1.7 )	0.4 ( 1.9 )
Change at Month 30 (n= 44, 45)	0.4 ( 1.4 )	0.1 ( 1.2 )
Change at Month 42 (n= 40, 34)	0.4 ( 1.2 )	0.2 ( 1.4 )

No statistical analyses for this end point

Secondary: Change From Baseline in Partial Mayo Score at Months 1, 3 and 6

Top of page

End point title

Change From Baseline in Partial Mayo Score at Months 1, 3 and 6

End point description

Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: subject’s recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score ranges from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, n= number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 1, 3 and 6

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Units on a scale
least squares mean (standard error)
Change at Month 1 (n= 67, 66)	0.2 ( 0.1 )	0.2 ( 0.1 )
Change at Month 3 (n= 64, 68)	0.3 ( 0.1 )	0.2 ( 0.1 )
Change at Month 6 (n= 60,69)	0.3 ( 0.1 )	0.3 ( 0.1 )

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 1

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.3

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 6

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.3

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 3

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.2

Secondary: Change From Baseline in Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Top of page

End point title

Change From Baseline in Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point description

Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: subject’s recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score ranges from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, ‘Number of Subjects Analysed’=subjects evaluable for this endpoint and n= number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	53	67
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Month 9 (n= 53, 67)	0.2 ( 0.8 )	0.2 ( 0.9 )
Change at Month 12 (n= 51, 63)	0.1 ( 0.7 )	0.2 ( 0.9 )
Change at Month 15 (n= 51, 57)	0.3 ( 1.2 )	0.1 ( 0.8 )
Change at Month 18 (n= 47, 56)	0.2 ( 0.8 )	0.2 ( 1.2 )
Change at Month 21 (n= 48, 54)	0.1 ( 0.7 )	0.4 ( 1.7 )
Change at Month 24 (n= 46, 50)	0.1 ( 0.6 )	0.0 ( 0.8 )
Change at Month 27 (n= 44, 48)	0.1 ( 0.6 )	0.1 ( 0.9 )
Change at Month 30 (n= 45, 45)	0.2 ( 0.8 )	0.1 ( 0.8 )
Change at Month 33 (n= 42, 41)	0.0 ( 0.5 )	0.2 ( 1.0 )
Change at Month 36 (n= 43, 41 )	0.0 ( 0.6 )	-0.1 ( 0.6 )
Change at Month 39 (n= 39, 34 )	0.1 ( 0.6 )	-0.1 ( 0.6 )
Change at Month 42 (n= 26,25)	0.1 ( 0.5 )	0.2 ( 1.1 )

No statistical analyses for this end point

Secondary: Number of Subjects With Mucosal Healing at Months 6, 18, 30 and 42

Top of page

End point title

Number of Subjects With Mucosal Healing at Months 6, 18, 30 and 42

End point description

Mucosal healing in subjects was defined as the mayo endoscopic subscore of 0 or 1. The Mayo endoscopic subscore consisted of the findings of centrally read flexible sigmoidoscopy, graded from 0 to 3 with higher scores indicated more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Months 6, 18, 30 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
Month 6	56	64
Month 18	43	56
Month 30	38	47
Month 42	36	36

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 6: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

11.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

23.1

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 18: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

18.6

Confidence interval

level

95%

sides

2-sided

lower limit

3.5

upper limit

32.6

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 30: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

12.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

28.1

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 42: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-16.1

upper limit

16.1

Secondary: Number of Subjects With Clinical Response Based on Mayo Score at Months 6, 18, 30 and 42

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End point title

Number of Subjects With Clinical Response Based on Mayo Score at Months 6, 18, 30 and 42

End point description

Clinical response was defined as a decrease from baseline in mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: subject’s recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a mayo score range of 0 to 12, where higher scores indicating more severe disease. FAS included all subjects who were randomised and received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Months 6, 18, 30 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
Month 6	59	67
Month 18	42	50
Month 30	41	48
Month 42	26	28

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 6: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

11.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 18: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

11.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

26.4

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 30: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

25.2

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

Statistical analysis description

Month 42: Adjusted (weighted) difference and its 95% CI based on normal approximation for the difference in binomial proportions.

Comparison groups

Tofacitinib 5 mg BID v Tofacitinib 10 mg BID

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Adjusted (weighted) difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

18.5

Secondary: Change From Baseline in Fecal Calprotectin at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

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End point title

Change From Baseline in Fecal Calprotectin at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point description

Change from baseline in fecal calprotectin (in micrograms per gram [mcg/g]) was reported. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, ‘Number of Subjects Analysed’ =subjects evaluable for this endpoint and n= number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	63	67
Units: Micrograms per gram
arithmetic mean (standard deviation)
Change at Month 1 (n= 63, 62)	-137.5 ( 980.6 )	-21.9 ( 304.7 )
Change at Month 3 (n= 57, 63)	-45.3 ( 1075.8 )	-38.5 ( 313.6 )
Change at Month 6 (n= 52, 67)	-24.1 ( 1444.6 )	-47.3 ( 331.4 )
Change at Month 9 (n= 48, 62)	-173.5 ( 1106.5 )	-59.3 ( 380.8 )
Change at Month 12 (n= 46, 54)	-28.8 ( 1113.4 )	-45.0 ( 350.7 )
Change at Month 15 (n= 45, 49)	-104.8 ( 1210.2 )	69.3 ( 480.5 )
Change at Month 18 (n= 39, 44)	-51.0 ( 1114.6 )	6.6 ( 565.4 )
Change at Month 21 (n= 43, 46)	-71.0 ( 1254.6 )	-29.3 ( 462.7 )
Change at Month 24 (n= 41, 43)	118.3 ( 1591.4 )	-69.8 ( 407.0 )
Change at Month 27 (n= 38, 39)	87.3 ( 478.8 )	-49.1 ( 366.3 )
Change at Month 30 (n= 36, 40)	-8.5 ( 458.5 )	-8.9 ( 518.5 )
Change at Month 33 (n= 36,38)	84.4 ( 434.5 )	-4.9 ( 484.8 )
Change at Month 36 (n= 38, 36)	230.7 ( 1162.5 )	-0.4 ( 449.4 )
Change at Month 39 (n= 28, 26)	-116.2 ( 472.8 )	-98.3 ( 532.9 )
Change at Month 42 (n= 24, 23)	-44.7 ( 278.9 )	-101.0 ( 452.0 )

No statistical analyses for this end point

Secondary: Change From Baseline in High Sensitivity C-Reactive Protein (hs-CRP) Level at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

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End point title

Change From Baseline in High Sensitivity C-Reactive Protein (hs-CRP) Level at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point description

Change From baseline in hs-CRP level (in milligrams per liter [mg/L]) was reported. FAS included all subjects who were randomised and received at least 1 dose of IP. Here, ‘Number of Subjects Analysed’ =subjects evaluable for this endpoint and n= number of subjects evaluable for each specified time point.

End point type

Secondary

End point timeframe

Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	63	67
Units: Milligrams per liter
arithmetic mean (standard deviation)
Change at Month 1 (n= 63, 67)	1.1 ( 9.8 )	-0.7 ( 3.4 )
Change at Month 3 (n= 56, 66)	0.7 ( 7.9 )	-0.2 ( 3.7 )
Change at Month 6 (n= 55, 66)	0.9 ( 5.8 )	0.1 ( 4.0 )
Change at Month 9 (n= 50, 63)	0.7 ( 11.1 )	1.1 ( 8.4 )
Change at Month 12 (n= 48, 59)	-0.3 ( 3.5 )	-0.2 ( 2.2 )
Change at Month 15 (n= 46, 51)	-0.7 ( 3.2 )	0.2 ( 2.4 )
Change at Month 18 (n= 43, 48)	1.0 ( 6.4 )	0.2 ( 1.9 )
Change at Month 21 (n= 44, 49)	-0.5 ( 3.3 )	-0.1 ( 1.4 )
Change at Month 24 (n= 40, 43)	-0.6 ( 3.0 )	-0.5 ( 2.2 )
Change at Month 27 (n= 39, 42)	-0.3 ( 2.8 )	0.7 ( 6.1 )
Change at Month 30 (n= 39, 44)	0.6 ( 4.1 )	-0.3 ( 1.9 )
Change at Month 33 (n= 38, 39)	0.1 ( 2.2 )	0.0 ( 3.9 )
Change at Month 36 (n= 38, 36)	-0.1 ( 3.1 )	-0.1 ( 3.9 )
Change at Month 39 (n= 37, 34)	-0.3 ( 3.5 )	2.8 ( 8.6 )
Change at Month 42 (n= 27, 25)	0.6 ( 3.7 )	5.9 ( 28.1 )

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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End point title

Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

End point description

An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE (TEAE) was defined as an event that emerged during the treatment period that was absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs included both serious and all non-serious adverse events (irrespective of frequency threshold used to report other AEs in safety section). Safety analysis set (SAS) included all subjects who received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Baseline up to 43 months

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
TEAEs	55	58
SAEs	7	16

No statistical analyses for this end point

Secondary: Number of Subjects With Serious Infections

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End point title

Number of Subjects With Serious Infections

End point description

Serious infections were defined as any infections (viral, bacterial, and fungal) requiring parenteral antimicrobial therapy, hospitalisation for treatment, or meeting other criteria that require the infection to be classified as serious adverse event. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. SAS included all subjects who received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Baseline up to 43 months

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects	3	6

No statistical analyses for this end point

Secondary: Number of Subjects With Clinical Laboratory Abnormalities

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End point title

Number of Subjects With Clinical Laboratory Abnormalities

End point description

Abnormality criteria: Haematology: haemoglobin(Hg):<0.8* lower limit of normal(LLN); haematocrit:<0.8*LLN; lymphocytes:<0.8*LLN; lymphocytes/leukocytes: <0.8*LLN; erythrocytes(ery.):<0.8*LLN; ery. mean corpuscular volume: <0.9*LLN; ery. mean corpuscular Hg: <0.9*LLN; reticulocytes, reticulocytes/ery.:>1.5*upper limit of normal(ULN); neutrophils, neutrophils/leukocytes: >1.2*ULN; basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes/leukocytes: >1.2*ULN; leukocyte esterase: >=1; Clinical chemistry: bicarbonate:<0.9*LLN, bilirubin(bil): >1.5*ULN; indirect bil: >1.5*ULN; aspartate aminotransferase(AT): >3.0*ULN; alanine AT: >3.0*ULN; gamma glutamyl transferase: >3.0*ULN; creatine kinase: >2.0*ULN; potassium: >1.1*ULN; blood urea nitrogen: >1.3*ULN; creatinine: >1.3*ULN; urate: >1.2*ULN; cholesterol: >1.3*ULN; HDL-cholesterol: <0.8*LLN; LDL-cholesterol: >1.2*ULN; triglycerides: >1.3*ULN; glucose: >1.5*ULN; urine Hg:>=1. SAS:all subjects who received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Baseline up to 27 months

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects	33	51

No statistical analyses for this end point

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities Leading to Study Treatment Discontinuation

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End point title

Number of Subjects With Clinically Significant Laboratory Abnormalities Leading to Study Treatment Discontinuation

End point description

Laboratory abnormalities leading to study treatment discontinuation: 2 sequential neutrophil counts <750 neutrophils per cubic millimeter (mm^3); 2 sequential lymphocyte counts <500 lymphocytes/mm^3; 2 sequential hemoglobin <8.0 grams per deciliter; 2 sequential platelet counts <75000 platelets/mm^3; 2 sequential AST or ALT elevations >=3*ULN with at least one total bilirubin value >=2*ULN; 2 sequential AST or ALT elevations >=3*ULN accompanied by signs or symptoms consistent with hepatic injury; 2 sequential AST or ALT elevations >=5*ULN; 2 sequential increases in creatinine >50% and >0.5 milligrams per deciliter over A3921139 baseline; 2 sequential CK elevations >10*ULN unless the causality is known not to be medically serious (eg, exercise induced). SAS: all subjects who received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Baseline up to 43 months

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects	1	1

No statistical analyses for this end point

Secondary: Number of Subjects With Vital Sign Abnormalities

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End point title

Number of Subjects With Vital Sign Abnormalities

End point description

Vital signs abnormality criteria included: 1) a) diastolic blood pressure (DBP) of (less than) <50 millimeter of mercury (mmHg), b) change greater than or equal to (>=) 20 mmHg increase, c) change >=20 mmHg decrease; 2) a) systolic blood pressure (SBP) of <90 mmHg, b) change >=30 mmHg increase, c) change >=30 mmHg decrease; 3) a) pulse rate value of <40 beats per minute (bpm), b) pulse rate >120 bpm. SAS included all subjects who received at least 1 dose of IP. Only those categories in which at least 1 subject had data were reported.

End point type

Secondary

End point timeframe

Baseline up to 43 months

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
DBP: <50 mmHg	3	0
DBP: Change >= 20mmHg increase	9	5
DBP: Change >= 20mmHg decrease	7	7
SBP: <90mmHg	2	0
SBP: Change >= 30mmHg increase	7	4
SBP: Change >= 30mmHg decrease	6	6

No statistical analyses for this end point

Secondary: Number of Subjects With Clinically Significant Physical Examinations Abnormalities

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End point title

Number of Subjects With Clinically Significant Physical Examinations Abnormalities

End point description

Physical examination included assessment of the weight, general appearance, eyes, mouth, lungs, heart, abdomen, musculoskeletal, extremities, skin and lymph nodes. Clinical significance was assessed by the investigator. SAS included all subjects who received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Baseline up to 43 months

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects	28	27

No statistical analyses for this end point

Secondary: Number of Subjects With Opportunistic Infections, all Malignancy, Gastrointestinal Perforation and Cardiovascular Events Adjudicated by Adjudication Committee

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End point title

Number of Subjects With Opportunistic Infections, all Malignancy, Gastrointestinal Perforation and Cardiovascular Events Adjudicated by Adjudication Committee

End point description

Number of subjects with adjudicated opportunistic infections including herpes zoster (non-adjacent or >2 adjacent dermatomes); all malignancies including non-melanoma skin cancer; gastrointestinal perforation and cardiovascular events including pulmonary embolism and cerebrovascular accident, adjudicated by adjudication committee were reported. SAS included all subjects who received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Baseline up to 43 months

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	70	70
Units: Subjects
Opportunistic Infections	0	1
All Malignancy	4	3
Gastrointestinal Perforation	0	0
Cardiovascular Events	2	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 43 months

Adverse event reporting additional description

Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorised as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Safety analysis set: all subjects who received at least 1 dose of investigational product.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects received tofacitinib 10 mg tablets (2 tablets of 5 mg), orally, twice daily up to 42 months. Subjects were followed-up to 4 weeks after the last dose.

Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects received tofacitinib 5 mg tablet with one tablet of matching placebo, orally, twice daily up to 42 months. Subjects were followed up to 4 weeks after the last dose.

Serious adverse events	Tofacitinib 10 mg BID	Tofacitinib 5 mg BID
Total subjects affected by serious adverse events
subjects affected / exposed	16 / 70 (22.86%)	7 / 70 (10.00%)
number of deaths (all causes)	1	0
number of deaths resulting from adverse events	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the vulva
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diffuse large B-cell lymphoma
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Limb injury
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Endometrial hyperplasia
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Breast disorder
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Colon dysplasia
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal stenosis
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
COVID-19
subjects affected / exposed	2 / 70 (2.86%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 70 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	2 / 70 (2.86%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Herpes zoster oticus
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 70 (1.43%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Tofacitinib 10 mg BID	Tofacitinib 5 mg BID
Total subjects affected by non serious adverse events
subjects affected / exposed	47 / 70 (67.14%)	47 / 70 (67.14%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
subjects affected / exposed	2 / 70 (2.86%)	1 / 70 (1.43%)
occurrences all number	2	2
Vascular disorders
Hypertension
subjects affected / exposed	5 / 70 (7.14%)	4 / 70 (5.71%)
occurrences all number	5	4
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	2 / 70 (2.86%)	2 / 70 (2.86%)
occurrences all number	2	2
Fatigue
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Chest pain
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Pyrexia
subjects affected / exposed	2 / 70 (2.86%)	5 / 70 (7.14%)
occurrences all number	3	5
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	2 / 70 (2.86%)	1 / 70 (1.43%)
occurrences all number	2	1
Respiratory disorder
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Cough
subjects affected / exposed	1 / 70 (1.43%)	3 / 70 (4.29%)
occurrences all number	2	3
Investigations
Lymphocyte count decreased
subjects affected / exposed	3 / 70 (4.29%)	1 / 70 (1.43%)
occurrences all number	3	1
Faecal calprotectin increased
subjects affected / exposed	3 / 70 (4.29%)	1 / 70 (1.43%)
occurrences all number	3	1
Blood creatine phosphokinase increased
subjects affected / exposed	5 / 70 (7.14%)	2 / 70 (2.86%)
occurrences all number	9	2
Aspartate aminotransferase increased
subjects affected / exposed	3 / 70 (4.29%)	0 / 70 (0.00%)
occurrences all number	5	0
SARS-CoV-2 test positive
subjects affected / exposed	7 / 70 (10.00%)	2 / 70 (2.86%)
occurrences all number	7	2
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	2 / 70 (2.86%)	0 / 70 (0.00%)
occurrences all number	2	0
Nervous system disorders
Headache
subjects affected / exposed	3 / 70 (4.29%)	4 / 70 (5.71%)
occurrences all number	3	5
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 70 (4.29%)	0 / 70 (0.00%)
occurrences all number	4	0
Lymphopenia
subjects affected / exposed	5 / 70 (7.14%)	2 / 70 (2.86%)
occurrences all number	5	2
Gastrointestinal disorders
Colitis ulcerative
subjects affected / exposed	14 / 70 (20.00%)	16 / 70 (22.86%)
occurrences all number	17	16
Large intestine polyp
subjects affected / exposed	3 / 70 (4.29%)	1 / 70 (1.43%)
occurrences all number	4	1
Abdominal pain
subjects affected / exposed	3 / 70 (4.29%)	5 / 70 (7.14%)
occurrences all number	5	8
Nausea
subjects affected / exposed	3 / 70 (4.29%)	3 / 70 (4.29%)
occurrences all number	3	3
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 70 (2.86%)	1 / 70 (1.43%)
occurrences all number	2	1
Diarrhoea
subjects affected / exposed	2 / 70 (2.86%)	4 / 70 (5.71%)
occurrences all number	2	4
Abdominal pain upper
subjects affected / exposed	2 / 70 (2.86%)	2 / 70 (2.86%)
occurrences all number	2	2
Haemorrhoids
subjects affected / exposed	2 / 70 (2.86%)	0 / 70 (0.00%)
occurrences all number	3	0
Rectal haemorrhage
subjects affected / exposed	0 / 70 (0.00%)	3 / 70 (4.29%)
occurrences all number	0	3
Mouth ulceration
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Pruritus
subjects affected / exposed	2 / 70 (2.86%)	1 / 70 (1.43%)
occurrences all number	2	1
Rash pruritic
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	2 / 70 (2.86%)	0 / 70 (0.00%)
occurrences all number	2	0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	2 / 70 (2.86%)	4 / 70 (5.71%)
occurrences all number	2	4
Arthritis
subjects affected / exposed	2 / 70 (2.86%)	1 / 70 (1.43%)
occurrences all number	2	1
Arthralgia
subjects affected / exposed	5 / 70 (7.14%)	4 / 70 (5.71%)
occurrences all number	5	6
Back pain
subjects affected / exposed	2 / 70 (2.86%)	3 / 70 (4.29%)
occurrences all number	2	4
Neck pain
subjects affected / exposed	2 / 70 (2.86%)	0 / 70 (0.00%)
occurrences all number	2	0
Osteoarthritis
subjects affected / exposed	2 / 70 (2.86%)	1 / 70 (1.43%)
occurrences all number	2	1
Infections and infestations
Bronchitis
subjects affected / exposed	5 / 70 (7.14%)	1 / 70 (1.43%)
occurrences all number	5	1
Herpes zoster
subjects affected / exposed	5 / 70 (7.14%)	2 / 70 (2.86%)
occurrences all number	5	2
Influenza
subjects affected / exposed	3 / 70 (4.29%)	1 / 70 (1.43%)
occurrences all number	3	2
Oral herpes
subjects affected / exposed	0 / 70 (0.00%)	5 / 70 (7.14%)
occurrences all number	0	8
Nasopharyngitis
subjects affected / exposed	8 / 70 (11.43%)	7 / 70 (10.00%)
occurrences all number	14	11
Upper respiratory tract infection
subjects affected / exposed	4 / 70 (5.71%)	3 / 70 (4.29%)
occurrences all number	5	5
COVID-19
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Clostridium difficile infection
subjects affected / exposed	0 / 70 (0.00%)	2 / 70 (2.86%)
occurrences all number	0	2
Sinusitis
subjects affected / exposed	1 / 70 (1.43%)	2 / 70 (2.86%)
occurrences all number	1	2
Urinary tract infection
subjects affected / exposed	1 / 70 (1.43%)	2 / 70 (2.86%)
occurrences all number	1	4
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	1 / 70 (1.43%)	2 / 70 (2.86%)
occurrences all number	1	2

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Were there any global substantial amendments to the protocol? Yes

30 Nov 2018

Protocol summary and section 3, study design were revised to change treatment duration from 18 months to 42 months. The purpose of this change was to gather additional long term safety data and to provide a longer time horizon to observe any potential divergence of efficacy between the two dose groups. Protocol summary, section 3, study design and section 9.1 sample size determination were revised to clarify that the final sample size may exceed 130 subjects. The purpose of this revision was to optimize recruitment of potentially eligible subjects from Study A3921139.

19 Jun 2019

As a result of the restrictions for prescriptions of tofacitinib set forth on 17 May 2019 by the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) in the European Union, a global amendment was incorporated. Subjects who were identified as having one or more of the contraindicated risk factors for pulmonary embolism as described by PRAC had their tofacitinib dose adjusted to open label 5 mg BID. Furthermore, any subject identified as having one or more of the contraindicated risk factors for pulmonary embolism as described by PRAC was not permitted to receive tofacitinib 10 mg BID. A risk factor check for pulmonary embolism was added for all study visits.

11 May 2020

As a result of the Sponsor determining that venous thromboembolism is an important identified risk/dose dependent adverse drug reaction for tofacitinib, a further global amendment regarding the monitoring and discontinuation guidelines for venous thromboembolism was incorporated. The changes described in the Protocol Administrative Clarification Letter for Amendment 2 due to COVID-19 were incorporated in the newly added Appendix 9.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
18 Mar 2022	The study terminated early due to business reasons, with the study already meeting its primary objective. The decision to terminate the trial was not based on any safety and/or efficacy concerns.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3b/4, Multi-Center, Double-Blind, Randomized, Parallel Group Study of Tofacitinib (CP-690,550) in Subjects With Ulcerative Colitis in Stable Remission

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects With Remission Based on Modified Mayo Score at Month 6

Primary: Number of Subjects With Remission Based on Modified Mayo Score at Month 6

Secondary: Time to Loss of Remission Based on Modified Mayo Score Using Kaplan-Meier Method

Secondary: Time to Loss of Remission Based on Modified Mayo Score Using Kaplan-Meier Method

Secondary: Number of Subjects With Remission Based on Modified Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Number of Subjects With Remission Based on Modified Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Number of Subjects With Remission Based on Total Mayo Score at Months 6, 18, 30 and 42

Secondary: Number of Subjects With Remission Based on Total Mayo Score at Months 6, 18, 30 and 42

Secondary: Number of Subjects With Remission Based on Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Number of Subjects With Remission Based on Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Number of Subjects With Remission Based on Modified Mayo Score at Months 18, 30 and 42

Secondary: Number of Subjects With Remission Based on Modified Mayo Score at Months 18, 30 and 42

Secondary: Change From Baseline in Modified Mayo Score at Month 6

Secondary: Change From Baseline in Modified Mayo Score at Month 6

Secondary: Change From Baseline in Modified Mayo Score at Months 18, 30 and 42

Secondary: Change From Baseline in Modified Mayo Score at Months 18, 30 and 42

Secondary: Change From Baseline in Modified Partial Mayo Score at Months 1, 3 and 6

Secondary: Change From Baseline in Modified Partial Mayo Score at Months 1, 3 and 6

Secondary: Change From Baseline in Modified Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Change From Baseline in Modified Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Change From Baseline in Total Mayo Score at Month 6

Secondary: Change From Baseline in Total Mayo Score at Month 6

Secondary: Change From Baseline in Total Mayo Score at Months 18, 30 and 42

Secondary: Change From Baseline in Total Mayo Score at Months 18, 30 and 42

Secondary: Change From Baseline in Partial Mayo Score at Months 1, 3 and 6

Secondary: Change From Baseline in Partial Mayo Score at Months 1, 3 and 6

Secondary: Change From Baseline in Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Change From Baseline in Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Number of Subjects With Mucosal Healing at Months 6, 18, 30 and 42

Secondary: Number of Subjects With Mucosal Healing at Months 6, 18, 30 and 42

Secondary: Number of Subjects With Clinical Response Based on Mayo Score at Months 6, 18, 30 and 42

Secondary: Number of Subjects With Clinical Response Based on Mayo Score at Months 6, 18, 30 and 42

Secondary: Change From Baseline in Fecal Calprotectin at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Change From Baseline in Fecal Calprotectin at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Change From Baseline in High Sensitivity C-Reactive Protein (hs-CRP) Level at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Change From Baseline in High Sensitivity C-Reactive Protein (hs-CRP) Level at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Serious Infections

Secondary: Number of Subjects With Serious Infections

Secondary: Number of Subjects With Clinical Laboratory Abnormalities

Secondary: Number of Subjects With Clinical Laboratory Abnormalities

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities Leading to Study Treatment Discontinuation

Secondary: Number of Subjects With Clinically Significant Laboratory Abnormalities Leading to Study Treatment Discontinuation

Secondary: Number of Subjects With Vital Sign Abnormalities

Secondary: Number of Subjects With Vital Sign Abnormalities

Secondary: Number of Subjects With Clinically Significant Physical Examinations Abnormalities

Secondary: Number of Subjects With Clinically Significant Physical Examinations Abnormalities

Secondary: Number of Subjects With Opportunistic Infections, all Malignancy, Gastrointestinal Perforation and Cardiovascular Events Adjudicated by Adjudication Committee

Secondary: Number of Subjects With Opportunistic Infections, all Malignancy, Gastrointestinal Perforation and Cardiovascular Events Adjudicated by Adjudication Committee

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 3b/4, Multi-Center, Double-Blind, Randomized, Parallel Group Study of Tofacitinib (CP-690,550) in Subjects With Ulcerative Colitis in Stable Remission