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Clinical Trial Results:
A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Of Oral CP-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis

Summary
EudraCT number	2011-004580-79
Trial protocol	DK CZ HU EE GB LV BE ES AT DE PL IT SK HR
Global end of trial date	27 May 2016

Results information
Results version number	v1(current)
This version publication date	23 Apr 2017
First version publication date	23 Apr 2017
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

A3921096

ISRCTN number

US NCT number

NCT01458574

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 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, 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

30 Nov 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 May 2016

Was the trial ended prematurely?

Main objective of the trial

1) To demonstrate the efficacy of tofacitinib as maintenance therapy in subjects with ulcerative colitis (UC). 2) To evaluate the safety and tolerability of tofacitinib as maintenance therapy in subjects with UC. 3) To evaluate the efficacy of tofacitinib maintenance therapy in achieving mucosal healing in subjects with UC. 4) To evaluate the tofacitinib pharmacokinetic exposure during maintenance therapy in subjects with UC. 5) To evaluate the effect of tofacitinib as maintenance therapy on quality-of-life in subjects with UC.

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 Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Jul 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 13

Country: Number of subjects enrolled

Belgium: 30

Country: Number of subjects enrolled

Czech Republic: 7

Country: Number of subjects enrolled

Germany: 25

Country: Number of subjects enrolled

Denmark: 7

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

Estonia: 4

Country: Number of subjects enrolled

France: 19

Country: Number of subjects enrolled

United Kingdom: 14

Country: Number of subjects enrolled

Croatia: 1

Country: Number of subjects enrolled

Hungary: 23

Country: Number of subjects enrolled

Israel: 7

Country: Number of subjects enrolled

Italy: 22

Country: Number of subjects enrolled

Latvia: 1

Country: Number of subjects enrolled

Netherlands: 14

Country: Number of subjects enrolled

Poland: 40

Country: Number of subjects enrolled

Romania: 6

Country: Number of subjects enrolled

Russian Federation: 19

Country: Number of subjects enrolled

Serbia: 20

Country: Number of subjects enrolled

Slovakia: 26

Country: Number of subjects enrolled

Ukraine: 39

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

United States: 114

Country: Number of subjects enrolled

Australia: 15

Country: Number of subjects enrolled

Brazil: 1

Country: Number of subjects enrolled

Colombia: 1

Country: Number of subjects enrolled

Japan: 39

Country: Number of subjects enrolled

Korea, Republic of: 23

Country: Number of subjects enrolled

New Zealand: 17

Country: Number of subjects enrolled

Taiwan: 1

Country: Number of subjects enrolled

South Africa: 22

Worldwide total number of subjects

593

EEA total number of subjects

261

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)

545

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Study subjects were enrolled from 196 investigational sites in Asia, Australia, Europe, North America, and South America. Overall, 593 subjects were randomized to study treatment. Study was conducted between 20 July 2012 and 27 May 2016.

Period 1 title

Overall Study (overall period)

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 milligram (mg) tablets, orally, twice daily (BID) for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Tofacitinib 5 mg tablets, orally, BID for 53 weeks of double blind treatment period.

Tofacitinib 10 mg BID

Arm description

Subjects received tofacitinib 10 mg tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Tofacitinib 10 mg tablets, orally, BID for 53 weeks of double blind treatment period.

Placebo

Arm description

Subjects received tofacitinib matched placebo tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Tofacitinib matched Placebo, orally, BID for 53 weeks of double blind treatment period.

Number of subjects in period 1	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Started	198	197	198
Treated	198	196	198
Completed	111	126	53
Not completed	87	71	145
Consent withdrawn by subject	6	3	5
Adverse event, non-fatal	5	9	7
Randomized but not treated	-	1	-
Pregnancy	1	1	-
Unspecified	2	1	-
Lost to follow-up	3	2	1
Lack of efficacy	70	53	132
Protocol deviation	-	1	-

Baseline characteristics

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Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects received tofacitinib 10 mg tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Reporting group title

Placebo

Reporting group description

Subjects received tofacitinib matched placebo tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Reporting group values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo	Total
Number of subjects	198	197	198	593
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants(gestational age <37 weeks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days - 23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	185	180	180	545
Adults (65-84 years)	13	17	18	48
Adults (85 years and over)	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	41.9 ( 13.7 )	42.9 ( 14.4 )	43.4 ( 14 )	-
Gender, Male/Female
Units: Subjects
Female	95	87	82	264
Male	103	110	116	329

End points

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Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects received tofacitinib 10 mg tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Reporting group title

Placebo

Reporting group description

Subjects received tofacitinib matched placebo tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Primary: Percentage of Subjects in Remission at Week 52

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End point title

Percentage of Subjects in Remission at Week 52

End point description

Remission in subjects 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 was an instrument designed to measure disease activity of ulcerative colitis (UC). It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and physician global assessment (PGA), each subscore graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12 where higher score indicating higher disease severity. Full analysis set (FAS) included all randomized subjects.

End point type

Primary

End point timeframe

Week 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	34.3	40.6	11.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

P-value based on Cochran-Mantel-Haenszel (CMH) chi-square test stratified by induction study treatment and baseline remission status. Difference and its 95 percent (%) confidence interval (CI) based on normal approximation for the difference in binomial proportions. Missing data were imputed using Non-responder imputation (NRI).

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

23.2

Confidence interval

level

95%

sides

2-sided

lower limit

15.3

upper limit

31.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

P-value based on CMH chi-square test stratified by induction study treatment and baseline remission status. Difference and its 95% CI based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

29.5

Confidence interval

level

95%

sides

2-sided

lower limit

21.4

upper limit

37.6

Secondary: Percentage of Subjects With Mucosal Healing at Week 52

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End point title

Percentage of Subjects With Mucosal Healing at Week 52

End point description

Mucosal healing in subjects was defined by 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 subscores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	37.4	45.7	13.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

24.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

32.5

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

32.6

Confidence interval

level

95%

sides

2-sided

lower limit

24.2

upper limit

Secondary: Percentage of Subjects in Sustained Steroid-Free Remission (Defined as Being in Remission and Steroid-Free at Both Week 24 and 52), Among Subjects With Remission at Baseline

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End point title

Percentage of Subjects in Sustained Steroid-Free Remission (Defined as Being in Remission and Steroid-Free at Both Week 24 and 52), Among Subjects With Remission at Baseline

End point description

Sustained steroid-free remission was defined by being in remission and steroid-free at both Week 24 and Week 52. Steroid-free remission was defined by being in remission, in addition to no requirement of any treatment with steroid for at least 4 weeks prior to the visit. Remission 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects. Here "number of subjects analyzed" signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	65	55	59
Units: percentage of subjects
number (not applicable)	35.4	47.3	5.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

P-value based on CMH chi-square test stratified by induction study treatment. Difference and its 95% CI based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

30.3

Confidence interval

level

95%

sides

2-sided

lower limit

17.4

upper limit

43.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

42.2

Confidence interval

level

95%

sides

2-sided

lower limit

27.9

upper limit

56.5

Secondary: Percentage of Subjects in Remission at Week 24

Top of page

End point title

Percentage of Subjects in Remission at Week 24

End point description

Remission in subjects 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher subscores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	33.8	35.5	11.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

22.7

Confidence interval

level

95%

sides

2-sided

lower limit

14.8

upper limit

30.6

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

24.4

Confidence interval

level

95%

sides

2-sided

lower limit

16.4

upper limit

32.4

Secondary: Percentage of Subjects in Sustained Remission

Top of page

End point title

Percentage of Subjects in Sustained Remission

End point description

Sustained remission in subjects was defined by being in remission at both Week 24 and Week 52. Remission 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher subscores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher score indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	22.2	25.4	5.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

17.2

Confidence interval

level

95%

sides

2-sided

lower limit

10.6

upper limit

23.7

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

20.3

Confidence interval

level

95%

sides

2-sided

lower limit

13.5

upper limit

27.1

Secondary: Percentage of Subjects With Mucosal Healing at Week 24

Top of page

End point title

Percentage of Subjects With Mucosal Healing at Week 24

End point description

Mucosal healing in subjects was defined by a 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 indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	43.9	46.2	17.2

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

26.8

Confidence interval

level

95%

sides

2-sided

lower limit

18.1

upper limit

35.5

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

20.3

upper limit

37.7

Secondary: Percentage of Subjects With Sustained Mucosal Healing

Top of page

End point title

Percentage of Subjects With Sustained Mucosal Healing

End point description

Sustained mucosal healing in subjects was defined by achieving mayo endoscopic subscore of 0 or 1 at both Week 24 and Week 52. The mayo endoscopic subscore consisted of the findings of centrally read flexible sigmoidoscopy, graded from 0 to 3 with higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	27.8	33	6.6

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

21.2

Confidence interval

level

95%

sides

2-sided

lower limit

14.1

upper limit

28.3

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

26.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

33.8

Secondary: Percentage of Subjects With Mucosal Healing at Week 24 and 52, Among Subjects With Mucosal Healing at Baseline

Top of page

End point title

Percentage of Subjects With Mucosal Healing at Week 24 and 52, Among Subjects With Mucosal Healing at Baseline

End point description

Mucosal healing in subjects was defined as achieving 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 indicating higher disease severity. FAS included all randomized subjects. Here "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	105	89	101
Units: percentage of subjects
number (not applicable)
Week 24	52.4	66.3	21.8
Week 52	41.9	55.1	11.9

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

At Week 24: P-value based on CMH chi-square test stratified by induction study treatment. Difference and its 95% CI based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

30.6

Confidence interval

level

95%

sides

2-sided

lower limit

18.1

upper limit

43.1

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

44.5

Confidence interval

level

95%

sides

2-sided

lower limit

31.8

upper limit

57.2

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

At Week 52: P-value based on CMH chi-square test stratified by induction study treatment. Difference and its 95% CI based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

18.7

upper limit

41.4

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

43.2

Confidence interval

level

95%

sides

2-sided

lower limit

31.1

upper limit

55.3

Secondary: Percentage of Subjects With Sustained Mucosal Healing, Among Subjects With Mucosal Healing at Baseline

Top of page

End point title

Percentage of Subjects With Sustained Mucosal Healing, Among Subjects With Mucosal Healing at Baseline

End point description

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	105	89	101
Units: percentage of subjects
number (not applicable)	33.3	49.4	8.9

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

24.4

Confidence interval

level

95%

sides

2-sided

lower limit

13.8

upper limit

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

40.5

Confidence interval

level

95%

sides

2-sided

lower limit

28.7

upper limit

52.3

Secondary: Percentage of Subjects With Clinical Response at Week 24 and 52

Top of page

End point title

Percentage of Subjects With Clinical Response at Week 24 and 52

End point description

Clinical response was defined by a decrease from induction study (A3921094 [NCT01465763] or A3921095 [NCT01458951]) baseline in Mayo score of at least 3 points and at least 30%, 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. Percentage of subjects with clinical response at Week 24 and 52 have been reported in this endpoint. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)
Week 24	63.6	70.6	33.3
Week 52	51.5	61.9	20.2

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

At Week 24: P-value based on CMH chi-square test stratified by induction study treatment and baseline remission status. Difference and its 95% CI based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

30.3

Confidence interval

level

95%

sides

2-sided

lower limit

20.9

upper limit

39.7

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

37.2

Confidence interval

level

95%

sides

2-sided

lower limit

28.1

upper limit

46.4

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

At Week 52: P-value based on CMH chi-square test stratified by induction study treatment and baseline remission status. Difference and its 95% CI based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

31.3

Confidence interval

level

95%

sides

2-sided

lower limit

22.4

upper limit

40.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

41.7

Confidence interval

level

95%

sides

2-sided

lower limit

32.9

upper limit

50.5

Secondary: Percentage of Subjects With Sustained Clinical Response

Top of page

End point title

Percentage of Subjects With Sustained Clinical Response

End point description

Sustained clinical response in subjects was defined as showing clinical response at both Week 24 and Week 52. Clinical response was defined by a decrease from induction study (A3921094 [NCT01465763] or A3921095 [NCT01458951]) baseline in mayo score of at least 3 points and at least 30%, 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. Percentage of subjects with sustained clinical response are reported in this endpoint. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	49	59.4	19.2

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

29.8

Confidence interval

level

95%

sides

2-sided

lower limit

20.9

upper limit

38.7

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

40.2

Confidence interval

level

95%

sides

2-sided

lower limit

31.4

upper limit

Secondary: Percentage of Subjects in Clinical Remission at Week 24 and 52

Top of page

End point title

Percentage of Subjects in Clinical Remission at Week 24 and 52

End point description

Clinical remission in subjects was defined as a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)
Week 24	34.3	35.5	11.1
Week 52	34.3	41.1	11.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

23.2

Confidence interval

level

95%

sides

2-sided

lower limit

15.3

upper limit

31.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

24.4

Confidence interval

level

95%

sides

2-sided

lower limit

16.4

upper limit

32.4

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

23.2

Confidence interval

level

95%

sides

2-sided

lower limit

15.3

upper limit

31.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

21.9

upper limit

38.2

Secondary: Percentage of Subjects in Sustained Clinical Remission

Top of page

End point title

Percentage of Subjects in Sustained Clinical Remission

End point description

Sustained clinical remission in subjects was defined as being in clinical remission at both Week 24 and Week 52. Clinical remission was defined by a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	22.2	25.9	5.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

17.2

Confidence interval

level

95%

sides

2-sided

lower limit

10.6

upper limit

23.7

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

20.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

27.7

Secondary: Percentage of Subjects in Deep Remission at Week 24 and 52

Top of page

End point title

Percentage of Subjects in Deep Remission at Week 24 and 52

End point description

Deep remission in subjects was defined as a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point and 0 subscore for both rectal bleeding and endoscopic subscores. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)
Week 24	14.1	10.7	4
Week 52	14.6	15.2	4

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

10.1

Confidence interval

level

95%

sides

2-sided

lower limit

4.5

upper limit

15.7

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0092

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

6.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

11.7

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

10.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

16.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

11.2

Confidence interval

level

95%

sides

2-sided

lower limit

5.5

upper limit

16.9

Secondary: Percentage of Subjects in Sustained Deep Remission

Top of page

End point title

Percentage of Subjects in Sustained Deep Remission

End point description

Sustained deep remission was defined by being in deep remission at both Week 24 and Week 52. Deep remission in subjects was defined as a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point and 0 subscore for both rectal bleeding and endoscopic subscores. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	6.1	3.6	0.5

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0029

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.035

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

5.8

Secondary: Percentage of Subjects in Symptomatic Remission at Week 24 and 52

Top of page

End point title

Percentage of Subjects in Symptomatic Remission at Week 24 and 52

End point description

Symptomatic remission in subjects was defined as a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point, and 0 subscore for both rectal bleeding and stool frequency. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 sub-scores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)
Week 24	23.7	21.8	6.6
Week 52	22.7	26.9	7.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

17.2

Confidence interval

level

95%

sides

2-sided

lower limit

10.3

upper limit

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

15.3

Confidence interval

level

95%

sides

2-sided

lower limit

8.5

upper limit

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

8.8

upper limit

22.5

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

19.8

Confidence interval

level

95%

sides

2-sided

lower limit

12.7

upper limit

Secondary: Percentage of Subjects in Sustained Symptomatic Remission

Top of page

End point title

Percentage of Subjects in Sustained Symptomatic Remission

End point description

Sustained symptomatic remission in subjects was defined as being in symptomatic remission at both Week 24 and Week 52. Symptomatic remission was defined as a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point, and 0 subscore for both rectal bleeding and stool frequency. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	13.6	15.7	2.5

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

11.1

Confidence interval

level

95%

sides

2-sided

lower limit

5.9

upper limit

16.4

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

13.2

Confidence interval

level

95%

sides

2-sided

lower limit

7.7

upper limit

18.7

Secondary: Percentage of Subjects in Endoscopic Remission at Week 24 and 52

Top of page

End point title

Percentage of Subjects in Endoscopic Remission at Week 24 and 52

End point description

Endoscopic remission in subjects was defined as a mayo endoscopic subscore of 0. The mayo endoscopic subscore consisted of the findings of centrally read flexible sigmoidoscopy, graded from 0 to 3 with higher subscores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)
Week 24	16.2	12.2	4
Week 52	14.6	16.8	4

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

12.1

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

17.9

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0021

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

13.5

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

10.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

16.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

12.7

Confidence interval

level

95%

sides

2-sided

lower limit

6.8

upper limit

18.6

Secondary: Percentage of Subjects in Sustained Endoscopic Remission

Top of page

End point title

Percentage of Subjects in Sustained Endoscopic Remission

End point description

Sustained endoscopic remission in subjects was defined as being in endoscopic remission at both Week 24 and Week 52. Endoscopic remission was defined by a mayo endoscopic subscore of 0. The mayo endoscopic subscore consisted of the findings of centrally read flexible sigmoidoscopy, graded from 0 to 3 with higher subscores indicating higher disease severity. FAS included all randomized subjects.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: percentage of subjects
number (not applicable)	6.1	5.1	0.5

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0029

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0064

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

7.8

Secondary: Total Mayo Score at Baseline, Week 24 and 52

Top of page

End point title

Total Mayo Score at Baseline, Week 24 and 52

End point description

Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. FAS included all randomized subjects. Here "n" signifies those subjects who were evaluable for specified categories, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n = 198, 197, 198)	3.3 ( 1.8 )	3.4 ( 1.8 )	3.3 ( 1.8 )
Week 24 (n = 179, 186, 181)	4.1 ( 3.4 )	4 ( 3.3 )	6.7 ( 3.5 )
Week 52 (n = 129, 137, 68)	3.2 ( 3.1 )	2.6 ( 2.7 )	4.6 ( 3.2 )

No statistical analyses for this end point

Secondary: Change from Baseline in Total Mayo Score at Week 24 and 52

Top of page

End point title

Change from Baseline in Total Mayo Score at Week 24 and 52

End point description

Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. Change from baseline in total mayo score at Week 24 and 52 was reported. FAS included all randomized subjects. Here "n" signifies those subjects who were evaluable for specified categories, respectively.

End point type

Secondary

End point timeframe

Baseline, Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	198	197	198
Units: units on a scale
least squares mean (standard error)
Change at Week 24 (n = 179, 186, 181)	0.3 ( 0.3 )	0 ( 0.3 )	2.9 ( 0.3 )
Change at Week 52 (n = 129, 137, 68)	0.4 ( 0.3 )	-0.4 ( 0.3 )	2.9 ( 0.4 )

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

At Week 24

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Linear mixed effect model

Parameter type

Least Square Mean Difference

Point estimate

-2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

-1.9

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

At Week 24

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Linear mixed effect model

Parameter type

Least Square Mean Difference

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

-2.2

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

At Week 52

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Linear mixed effect model

Parameter type

Least Square Mean Difference

Point estimate

-2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

-1.7

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

At Week 52

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

395

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Linear mixed effect model

Parameter type

Least Square Mean Difference

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

-2.5

Secondary: Percentage of Subjects in Remission, Among Subjects With Remission at Baseline

Top of page

End point title

Percentage of Subjects in Remission, Among Subjects With Remission at Baseline

End point description

Remission in subjects 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher score indicating higher disease severity. FAS included all randomized subjects. Here "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	65	55	59
Units: percentage of subjects
number (not applicable)
Week 24	55.4	63.6	15.3
Week 52	46.2	56.4	10.2

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

40.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

55.3

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

48.4

Confidence interval

level

95%

sides

2-sided

lower limit

32.7

upper limit

64.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

21.6

upper limit

50.3

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

46.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

61.4

Secondary: Percentage of Subjects in Sustained Remission, Among Subjects With Remission at Baseline

Top of page

End point title

Percentage of Subjects in Sustained Remission, Among Subjects With Remission at Baseline

End point description

Sustained remission in subjects was defined by being in remission at both Week 24 and Week 52. Remission was defined as 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher score indicating higher disease severity. FAS included all randomized subjects. Here "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	65	55	59
Units: percentage of subjects
number (not applicable)	36.9	47.3	5.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

31.8

Confidence interval

level

95%

sides

2-sided

lower limit

18.8

upper limit

44.8

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

42.2

Confidence interval

level

95%

sides

2-sided

lower limit

27.9

upper limit

56.5

Secondary: Percentage of Subjects in Steroid-free Remission, Among Subjects in Remission at Baseline

Top of page

End point title

Percentage of Subjects in Steroid-free Remission, Among Subjects in Remission at Baseline

End point description

Steroid-free remission was defined by being in remission, in addition to no requirement of any treatment with steroid for at least 4 weeks prior to the visit. Remission 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 was an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12, where higher scores indicating higher disease severity. Percentage of subjects in steroid-free remission were reported in this endpoint. FAS included all randomized subjects. Here "number of subjects analyzed" signifies those subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	65	55	59
Units: percentage of subjects
number (not applicable)
Week 24	53.8	63.6	15.3
Week 52	44.6	56.4	10.2

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

38.6

Confidence interval

level

95%

sides

2-sided

lower limit

23.4

upper limit

53.8

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

48.4

Confidence interval

level

95%

sides

2-sided

lower limit

32.7

upper limit

64.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

34.4

Confidence interval

level

95%

sides

2-sided

lower limit

20.1

upper limit

48.8

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

46.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

61.4

Secondary: Percentage of Subjects in Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

Top of page

End point title

Percentage of Subjects in Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

End point description

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	101	87	101
Units: percentage of subjects
number (not applicable)
Week 24	23.8	24.1	10.9
Week 52	27.7	27.6	10.9

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0074

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

12.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

23.2

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0103

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

13.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

24.1

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

16.8

Confidence interval

level

95%

sides

2-sided

lower limit

6.2

upper limit

27.5

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0029

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

16.7

Confidence interval

level

95%

sides

2-sided

lower limit

5.5

upper limit

27.9

Secondary: Percentage of Subjects in Sustained Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

Top of page

End point title

Percentage of Subjects in Sustained Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

End point description

End point type

Secondary

End point timeframe

Week 24, 52

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo
Number of subjects analysed	101	87	101
Units: percentage of subjects
number (not applicable)	12.9	16.1	5

Tofacitinib 5 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 5 mg BID v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0419

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

7.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

15.7

Tofacitinib 10 mg BID, Placebo

Statistical analysis description

Comparison groups

Tofacitinib 10 mg BID v Placebo

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0121

Method

CMH chi-square test

Parameter type

Difference in percentage

Point estimate

11.1

Confidence interval

level

95%

sides

2-sided

lower limit

2.3

upper limit

19.9

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline up to Week 57

Adverse event reporting additional description

Same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event. Safety analysis included all treated subjects.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects received tofacitinib 5 mg tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Reporting group title

Placebo

Reporting group description

Subjects received tofacitinib matched placebo tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects received tofacitinib 10 mg tablets, orally, BID for 53 weeks of double blind treatment period. Subjects were followed-up for 4 weeks if withdrew from study participation.

Serious adverse events	Tofacitinib 5 mg BID	Placebo	Tofacitinib 10 mg BID
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 198 (5.05%)	13 / 198 (6.57%)	11 / 196 (5.61%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Invasive ductal breast carcinoma
Additional description: This AE was gender specific.
subjects affected / exposed ^[1]	0 / 95 (0.00%)	1 / 82 (1.22%)	0 / 86 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Lower limb fracture
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Embolism venous
subjects affected / exposed	0 / 198 (0.00%)	1 / 198 (0.51%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
Additional description: This AE was gender specific.
subjects affected / exposed ^[2]	1 / 95 (1.05%)	0 / 82 (0.00%)	0 / 86 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malaise
subjects affected / exposed	0 / 198 (0.00%)	1 / 198 (0.51%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	2 / 198 (1.01%)	8 / 198 (4.04%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 2	0 / 8	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 198 (0.00%)	1 / 198 (0.51%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis acneiform
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spondylolisthesis
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacterial diarrhoea
subjects affected / exposed	0 / 198 (0.00%)	0 / 198 (0.00%)	1 / 196 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 198 (0.00%)	1 / 198 (0.51%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 198 (0.00%)	1 / 198 (0.51%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 198 (0.51%)	0 / 198 (0.00%)	0 / 196 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This AE was gender specific
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This AE was gender specific

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Tofacitinib 5 mg BID	Placebo	Tofacitinib 10 mg BID
Total subjects affected by non serious adverse events
subjects affected / exposed	87 / 198 (43.94%)	108 / 198 (54.55%)	107 / 196 (54.59%)
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	6 / 198 (3.03%)	4 / 198 (2.02%)	13 / 196 (6.63%)
occurrences all number	8	4	16
Nervous system disorders
Headache
subjects affected / exposed	17 / 198 (8.59%)	12 / 198 (6.06%)	6 / 196 (3.06%)
occurrences all number	21	14	8
General disorders and administration site conditions
Fatigue
subjects affected / exposed	8 / 198 (4.04%)	11 / 198 (5.56%)	4 / 196 (2.04%)
occurrences all number	8	12	4
Gastrointestinal disorders
Abdominal pain
alternative assessment type: Systematic
subjects affected / exposed	5 / 198 (2.53%)	11 / 198 (5.56%)	7 / 196 (3.57%)
occurrences all number	5	13	9
Colitis ulcerative
subjects affected / exposed	35 / 198 (17.68%)	64 / 198 (32.32%)	29 / 196 (14.80%)
occurrences all number	41	65	30
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	6 / 198 (3.03%)	8 / 198 (4.04%)	11 / 196 (5.61%)
occurrences all number	6	8	12
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	17 / 198 (8.59%)	19 / 198 (9.60%)	17 / 196 (8.67%)
occurrences all number	21	22	19
Infections and infestations
Herpes zoster
subjects affected / exposed	2 / 198 (1.01%)	1 / 198 (0.51%)	10 / 196 (5.10%)
occurrences all number	2	1	11
Nasopharyngitis
subjects affected / exposed	19 / 198 (9.60%)	11 / 198 (5.56%)	27 / 196 (13.78%)
occurrences all number	21	23	39
Upper respiratory tract infection
subjects affected / exposed	13 / 198 (6.57%)	7 / 198 (3.54%)	12 / 196 (6.12%)
occurrences all number	15	8	14
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	4 / 198 (2.02%)	2 / 198 (1.01%)	11 / 196 (5.61%)
occurrences all number	5	2	11

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

28 Sep 2012

This amendment updated standard Pfizer protocol text, including safety language in various sections, including Administration, Reproductive Status of Female Subjects, and AE Reporting. In addition, this amendment included updates to the summary of safety section for tofacitinib to be consistent with the revised investigator's brochure (IB), secondary study endpoints, schedule of activities flowchart, and prohibited medication list. Guidelines and clarifications were included which provided instruction for dosage adjustment, temporary withholding of study drug, and scheduled study visit procedures.

20 Apr 2016

This administrative amendment clarified the multiple comparison procedure stated in Section 9.2.2 so that it guaranteed the control of the family-wise Type I error rate at 0.05.

Were there any global interruptions to the trial? No

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 Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Of Oral CP-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects in Remission at Week 52

Primary: Percentage of Subjects in Remission at Week 52

Secondary: Percentage of Subjects With Mucosal Healing at Week 52

Secondary: Percentage of Subjects With Mucosal Healing at Week 52

Secondary: Percentage of Subjects in Sustained Steroid-Free Remission (Defined as Being in Remission and Steroid-Free at Both Week 24 and 52), Among Subjects With Remission at Baseline

Secondary: Percentage of Subjects in Sustained Steroid-Free Remission (Defined as Being in Remission and Steroid-Free at Both Week 24 and 52), Among Subjects With Remission at Baseline

Secondary: Percentage of Subjects in Remission at Week 24

Secondary: Percentage of Subjects in Remission at Week 24

Secondary: Percentage of Subjects in Sustained Remission

Secondary: Percentage of Subjects in Sustained Remission

Secondary: Percentage of Subjects With Mucosal Healing at Week 24

Secondary: Percentage of Subjects With Mucosal Healing at Week 24

Secondary: Percentage of Subjects With Sustained Mucosal Healing

Secondary: Percentage of Subjects With Sustained Mucosal Healing

Secondary: Percentage of Subjects With Mucosal Healing at Week 24 and 52, Among Subjects With Mucosal Healing at Baseline

Secondary: Percentage of Subjects With Mucosal Healing at Week 24 and 52, Among Subjects With Mucosal Healing at Baseline

Secondary: Percentage of Subjects With Sustained Mucosal Healing, Among Subjects With Mucosal Healing at Baseline

Secondary: Percentage of Subjects With Sustained Mucosal Healing, Among Subjects With Mucosal Healing at Baseline

Secondary: Percentage of Subjects With Clinical Response at Week 24 and 52

Secondary: Percentage of Subjects With Clinical Response at Week 24 and 52

Secondary: Percentage of Subjects With Sustained Clinical Response

Secondary: Percentage of Subjects With Sustained Clinical Response

Secondary: Percentage of Subjects in Clinical Remission at Week 24 and 52

Secondary: Percentage of Subjects in Clinical Remission at Week 24 and 52

Secondary: Percentage of Subjects in Sustained Clinical Remission

Secondary: Percentage of Subjects in Sustained Clinical Remission

Secondary: Percentage of Subjects in Deep Remission at Week 24 and 52

Secondary: Percentage of Subjects in Deep Remission at Week 24 and 52

Secondary: Percentage of Subjects in Sustained Deep Remission

Secondary: Percentage of Subjects in Sustained Deep Remission

Secondary: Percentage of Subjects in Symptomatic Remission at Week 24 and 52

Secondary: Percentage of Subjects in Symptomatic Remission at Week 24 and 52

Secondary: Percentage of Subjects in Sustained Symptomatic Remission

Secondary: Percentage of Subjects in Sustained Symptomatic Remission

Secondary: Percentage of Subjects in Endoscopic Remission at Week 24 and 52

Secondary: Percentage of Subjects in Endoscopic Remission at Week 24 and 52

Secondary: Percentage of Subjects in Sustained Endoscopic Remission

Secondary: Percentage of Subjects in Sustained Endoscopic Remission

Secondary: Total Mayo Score at Baseline, Week 24 and 52

Secondary: Total Mayo Score at Baseline, Week 24 and 52

Secondary: Change from Baseline in Total Mayo Score at Week 24 and 52

Secondary: Change from Baseline in Total Mayo Score at Week 24 and 52

Secondary: Percentage of Subjects in Remission, Among Subjects With Remission at Baseline

Secondary: Percentage of Subjects in Remission, Among Subjects With Remission at Baseline

Secondary: Percentage of Subjects in Sustained Remission, Among Subjects With Remission at Baseline

Secondary: Percentage of Subjects in Sustained Remission, Among Subjects With Remission at Baseline

Secondary: Percentage of Subjects in Steroid-free Remission, Among Subjects in Remission at Baseline

Secondary: Percentage of Subjects in Steroid-free Remission, Among Subjects in Remission at Baseline

Secondary: Percentage of Subjects in Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

Secondary: Percentage of Subjects in Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

Secondary: Percentage of Subjects in Sustained Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

Secondary: Percentage of Subjects in Sustained Steroid-Free Remission, Among Subjects Receiving Steroids at Baseline

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Of Oral CP-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis