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Clinical Trial Results:
A Multi-center, Open-Label Study of CP-690,550 in Subjects With Moderate to Severe Ulcerative Colitis

Summary
EudraCT number	2011-004581-14
Trial protocol	CZ DK HU EE GB LV BE NL ES AT DE SK PL IT HR
Global end of trial date	06 Aug 2020

Results information
Results version number	v1(current)
This version publication date	19 Aug 2021
First version publication date	19 Aug 2021
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

A3921139

ISRCTN number

-

US NCT number

NCT01470612

WHO universal trial number (UTN)

-

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

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

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

16 Mar 2021

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

06 Aug 2020

Was the trial ended prematurely?

No

Main objective of the trial

To assess the safety and tolerability of long-term tofacitinib therapy in subjects with ulcerative colitis (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 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

01 Oct 2012

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 30

Country: Number of subjects enrolled

Austria: 30

Country: Number of subjects enrolled

Belgium: 61

Country: Number of subjects enrolled

Brazil: 2

Country: Number of subjects enrolled

Canada: 28

Country: Number of subjects enrolled

Colombia: 2

Country: Number of subjects enrolled

Croatia: 1

Country: Number of subjects enrolled

Czechia: 15

Country: Number of subjects enrolled

Denmark: 14

Country: Number of subjects enrolled

Estonia: 8

Country: Number of subjects enrolled

France: 29

Country: Number of subjects enrolled

Germany: 50

Country: Number of subjects enrolled

Hungary: 32

Country: Number of subjects enrolled

Israel: 6

Country: Number of subjects enrolled

Italy: 23

Country: Number of subjects enrolled

Japan: 53

Country: Number of subjects enrolled

Korea, Republic of: 51

Country: Number of subjects enrolled

Latvia: 1

Country: Number of subjects enrolled

Netherlands: 32

Country: Number of subjects enrolled

New Zealand: 29

Country: Number of subjects enrolled

Poland: 56

Country: Number of subjects enrolled

Romania: 9

Country: Number of subjects enrolled

Russian Federation: 33

Country: Number of subjects enrolled

Serbia: 34

Country: Number of subjects enrolled

Slovakia: 33

Country: Number of subjects enrolled

South Africa: 26

Country: Number of subjects enrolled

Spain: 21

Country: Number of subjects enrolled

Taiwan: 1

Country: Number of subjects enrolled

Ukraine: 47

Country: Number of subjects enrolled

United Kingdom: 21

Country: Number of subjects enrolled

United States: 166

Worldwide total number of subjects

944

EEA total number of subjects

415

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

881

From 65 to 84 years

63

85 years and over

0

Subject disposition

Top of page

Recruitment details

Subjects enrolled in this Study A3921139: 1) who had completed or had early withdrawal due to treatment failure in Study A3921096 (NCT01458574) 2) or who were non-responders after completing induction studies A3921094 (NCT01465763) or A3921095 (NCT01458951). Eligible participants were assigned to either Tofacitinib 5 mg BID or 10 mg BID group.

Screening details

Treatment failure for A3921096: Increase in Mayo score of >=3 points from baseline and rectal bleeding sub score by >=1 point and endoscopic sub score of >=1 point post minimum of 8 weeks treatment. If endoscopic sub score and baseline endoscopic sub score was 3 (maximum), then increase by >=1 point was not needed, but all other criteria must met.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Tofacitinib 5 mg BID

Arm description

Subjects who completed Study A3921096 and were in remission at Week 52 of Study A3921096, received Tofacitinib 5 milligram (mg) tablets twice daily (BID) for maximum of 80 months in this Study A3921139. Remission was defined as total Mayo score less than or equal to (<=) 2 with no individual sub score greater than (>)1 and rectal bleeding sub score of 0.

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

Subjects received Tofacitinib 5 mg tablets orally twice daily.

Tofacitinib 10 mg BID

Arm description

Subjects who had completed Study A3921096 and not in remission, or who had early withdrawal due to treatment failure from Study A3921096, or who were non responders after completing A3921094 or A3921095 received Tofacitinib 10 mg tablets twice daily for maximum of 84 months in this Study A3921139.

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

Subjects received Tofacitinib 10 mg tablets orally twice daily.

Number of subjects in period 1	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Started	175	769
Completed	91	104
Not completed	84	665
Adverse event, serious fatal	-	1
Consent withdrawn by subject	24	79
Did not meet entrance criteria	-	1
Adverse event, non-fatal	20	80
Pregnancy	2	10
Unspecified	14	156
Lost to follow-up	2	5
Lack of efficacy	20	326
Protocol deviation	2	7

Baseline characteristics

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Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects who completed Study A3921096 and were in remission at Week 52 of Study A3921096, received Tofacitinib 5 milligram (mg) tablets twice daily (BID) for maximum of 80 months in this Study A3921139. Remission was defined as total Mayo score less than or equal to (<=) 2 with no individual sub score greater than (>)1 and rectal bleeding sub score of 0.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects who had completed Study A3921096 and not in remission, or who had early withdrawal due to treatment failure from Study A3921096, or who were non responders after completing A3921094 or A3921095 received Tofacitinib 10 mg tablets twice daily for maximum of 84 months in this Study A3921139.

Reporting group values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Total
Number of subjects	175	769	944
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	161	720	881
From 65-84 years	14	49	63
85 years and over	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	44.5 ( 14.6 )	40.5 ( 13.5 )	-
Sex: Female, Male
Units: subjects
Female	79	310	389
Male	96	459	555
Race/Ethnicity, Customized
Units: Subjects
White	136	615	751
Black	0	9	9
Asian	25	97	122
Other	9	24	33
Unspecified	5	24	29

End points

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Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects who completed Study A3921096 and were in remission at Week 52 of Study A3921096, received Tofacitinib 5 milligram (mg) tablets twice daily (BID) for maximum of 80 months in this Study A3921139. Remission was defined as total Mayo score less than or equal to (<=) 2 with no individual sub score greater than (>)1 and rectal bleeding sub score of 0.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects who had completed Study A3921096 and not in remission, or who had early withdrawal due to treatment failure from Study A3921096, or who were non responders after completing A3921094 or A3921095 received Tofacitinib 10 mg tablets twice daily for maximum of 84 months in this Study A3921139.

Primary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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End point title

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) ^[1]

End point description

An AE was any untoward medical occurrence in a subject who received study drug 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. Treatment-emergent were events between first dose of study drug and up to 81 months for Tofacitininb 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. Safety analysis set (SAS) included all subjects who received at least 1 dose of study medication in this study.

End point type

Primary

End point timeframe

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects
Subject with AEs	154	626
Subject with SAEs	39	147

No statistical analyses for this end point

Primary: Number of Subjects With Serious Infections as Treatment Emergent Adverse Events (TEAEs)

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End point title

Number of Subjects With Serious Infections as Treatment Emergent Adverse Events (TEAEs) ^[2]

End point description

Serious infections were treated infections that required parenteral antimicrobial therapy or hospitalization for treatment or; met other criteria that required the infection to be classified as a serious adverse event (SAE). 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. Treatment-emergent were events between first dose of study drug and up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group that were absent before treatment or that worsened relative to pretreatment state. SAS included all subjects who received at least 1 dose of study medication in this study.

End point type

Primary

End point timeframe

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects	8	31

No statistical analyses for this end point

Primary: Number of Subjects With Laboratory Test Abnormalities

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End point title

Number of Subjects With Laboratory Test Abnormalities ^[3]

End point description

Laboratory abnormalities: Hb, hematocrit, RBC: <0.8*LLN; reticulocytes (absolute [Abs], %):<0.5*LLN,>1.5*ULN; MCV,MCH:<0.9*LLN,>1.1*ULN;platelets:<0.5*LLN,>1.75*ULN;WBC:<0.6*LLN,>1.5*ULN;lymphocytes (Abs,%), total neutrophils(Abs,%):<0.8*LLN,>1.2* ULN;Basophils(Abs,%),eosinophils(Abs,%),monocytes(Abs,%):>1.2*ULN; total bilirubin,direct and indirect bilirubin:>1.5* ULN;AST,ALT,gamma GT,LDH,ALP:>3.0* ULN;total protein,albumin:<0.8* LLN,>1.2*ULN:BUN,creatinine: >1.3*ULN;uric acid:>1.2*ULN;cholesterol,triglycerides:>1.3*ULN;cholesterol (HDL: <0.8*LLN;LDL:>1.2*ULN);sodium:<0.95*LLN,>1.05*ULN;potassium,chloride,calcium,bicarbonate:<0.9*LLN, >1.1*ULN; glucose: <0.6*LLN; creatine kinase >2.0*ULN; urine specific gravity: <1.003; urine pH: <4.5; urine (glucose,protein,blood,nitrite,leukocyte,esterase): >=1; Urine (RBC,WBC):>=20;urine epithelial cells:>=6; urine (casts,granular casts,hyaline casts): >1; urine bacteria:>20. SAS. "Number of subjects Analysed"=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	761
Units: subjects	162	670

No statistical analyses for this end point

Primary: Number of Subjects With Vital Sign Abnormalities

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End point title

Number of Subjects With Vital Sign Abnormalities ^[4]

End point description

Vital sign abnormalities included >=30 millimeter of mercury [mmHg] increase in systolic blood pressure (BP), >=30 mmHg decrease in systolic BP, Systolic BP (<90 mmHg), >=20 mmHg increase in diastolic BP, >=20 mmHg decrease in diastolic BP, diastolic BP (<50 mmHg), pulse rate (<40 beats per minute [BPM]), pulse rate (>120 BPM). SAS included all subjects who received at least 1 dose of study medication in this study. Here, "Number of subjects analysed" signifies subjects evaluable for this endpoint and "n" signifies subjects evaluable at each specified category.

End point type

Primary

End point timeframe

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	763
Units: subjects
Systolic BP (>=30 mmHg increase) (n=172, 748)	20	113
Systolic BP (>=30 mmHg decrease) (n=172, 748)	19	44
Systolic BP (<90 mmHg) (n=175, 763)	3	13
Diastolic BP (>=20 mmHg increase) (n=172, 748)	21	137
Diastolic BP (>=20 mmHg decrease) (n=172, 748)	37	78
Diastolic BP (<50 mmHg) (n=175, 763)	3	16
Pulse Rate (<40 BPM) (n=175, 763)	1	0
Pulse Rate (>120 BPM) (n=175, 763)	0	8

No statistical analyses for this end point

Primary: Number of Subjects With Clinically Significant Changes in Physical Examinations From Baseline

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End point title

Number of Subjects With Clinically Significant Changes in Physical Examinations From Baseline ^[5]

End point description

Physical examinations included weight, general appearance, head, ears, eyes, nose, mouth, throat, thyroid, skin (presence of rash), lungs (auscultation), heart (auscultation for presence of murmurs, gallops, rubs, peripheral edema), abdominal (palpation and auscultation), perianal, musculoskeletal, extremities, neurologic (mental status, gait, reflexes, motor and sensory function, coordination) and lymph nodes. Clinically significant changes were judged by the investigator. SAS included all subjects who received at least 1 dose of study medication in this study.

End point type

Primary

End point timeframe

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects	84	391

No statistical analyses for this end point

Primary: Number of Subjects With Electrocardiogram (ECG) Abnormalities

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End point title

Number of Subjects With Electrocardiogram (ECG) Abnormalities ^[6]

End point description

ECG abnormalities criteria: maximum PR interval (>=300 millisecond); maximum QRS complex (>=200 millisecond); and maximum QT interval (>=500 millisecond). SAS included all subjects who received at least 1 dose of study medication in this study. Here, "Number of subjects analyzed" signifies number of subjects evaluable for this endpoint and "n" signifies subjects evaluable at each specified category.

End point type

Primary

End point timeframe

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	158	707
Units: subjects
Maximum PR interval (>=300) (n=157,706)	0	0
Maximum QRS complex (>=200)(n=158,707)	0	0
Maximum QT interval (>=500)(n=158,707)	0	0

No statistical analyses for this end point

Primary: Incidence Rates for Adjudicated Cardiovascular, Malignancy, Opportunistic Infections and Thromboembolic Safety Events

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End point title

Incidence Rates for Adjudicated Cardiovascular, Malignancy, Opportunistic Infections and Thromboembolic Safety Events ^[7]

End point description

Incidence rates (number of subjects with events per 100 subjects-years) for adjudicated cardiovascular (major adverse cardiovascular event [MACE]), malignancy (non-melanoma skin cancer [NMSC], malignancy excluding NMSC, opportunistic infections (OIs) (both herpes zoster and non herpes zoster OIs) and thromboembolic events (venous thromboembolism) safety events was analyzed.

End point type

Primary

End point timeframe

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: Incidence rate
number (confidence interval 95%)
MACE	0.31 (0.04 to 1.13)	0.11 (0.01 to 0.40)
NMSC	0.96 (0.35 to 2.08)	0.68 (0.35 to 1.19)
Malignancies excluding NMSC	1.09 (0.44 to 2.25)	1.00 (0.60 to 1.59)
Herpes Zoster OI	0.47 (0.10 to 1.37)	0.79 (0.43 to 1.32)
Non Herpes Zoster OI	0.16 (0.00 to 0.87)	0.17 (0.03 to 0.49)
Venous thromboembolism	0.00 (0.00 to 0.57)	0.33 (0.12 to 0.73)

No statistical analyses for this end point

Secondary: Number of Subjects in Remission at Months 2, 12, 24 and 36: Observed Cases

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End point title

Number of Subjects in Remission at Months 2, 12, 24 and 36: Observed Cases

End point description

Remission in subjects was defined as a total Mayo score of less than or equals to (<=) 2, with no individual sub score exceeding 1 point and a rectal bleeding sub score of 0. Mayo score was an instrument designed to measure disease activity of ulcerative colitis (UC). It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and physician global assessment (PGA), each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total score range of 0 to 12, where higher score indicated more severe disease. FAS included all subjects who received at least 1 dose of study medication in this study. Here, "Number of subjects analysed" signifies subjects evaluable for this endpoint and "n" signifies subjects evaluable at each specified timepoint. Data is presented for observed cases, no imputation technique was applied.

End point type

Secondary

End point timeframe

Months 2, 12, 24 and 36

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	164	676
Units: subjects
Month 2 (n= 164, 676)	131	188
Month 12 (n= 154, 447)	129	279
Month 24 (n= 132, 371)	103	264
Month 36 (n= 113, 299)	98	239

No statistical analyses for this end point

Secondary: Number of Subjects in Remission at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

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End point title

Number of Subjects in Remission at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

End point description

Remission in subjects was defined as a total Mayo score of <=2, with no individual sub score exceeding 1 point and a rectal bleeding sub score of 0. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total score range of 0 to 12, where higher score indicated more severe disease. FAS included all subjects who received at least 1 dose of study medication in this study. NRI method was used for missing data except for visits after a subject advanced to other studies where LOCF method was used.

End point type

Secondary

End point timeframe

Months 2, 12, 24 and 36

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects
Month 2	131	188
Month 12	129	279
Month 24	103	264
Month 36	103	259

No statistical analyses for this end point

Secondary: Number of Subjects in Clinical Remission at Months 2, 12, 24 and 36: Observed Cases

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End point title

Number of Subjects in Clinical Remission at Months 2, 12, 24 and 36: Observed Cases

End point description

Clinical remission in subjects was defined as a total mayo score of <=2 with no individual sub score exceeding 1 point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total score range of 0 to 12, where higher score indicated more severe disease. Here, "Number of subjects analysed" signifies subjects evaluable for this endpoint and "n" signifies subjects evaluable at each specified time point. Data is presented for observed cases, no imputation technique was applied.

End point type

Secondary

End point timeframe

Months 2, 12, 24 and 36

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	164	676
Units: subjects
Month 2 (n= 164, 676)	132	191
Month 12 (n= 154, 447)	129	282
Month 24 (n= 132, 371)	104	266
Month 36 (n= 113, 299)	102	240

No statistical analyses for this end point

Secondary: Number of Subjects in Clinical Remission at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

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End point title

Number of Subjects in Clinical Remission at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

End point description

Clinical remission in subjects was defined as a total mayo score of <=2 with no individual sub score exceeding 1 point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total score range of 0 to 12, where higher score indicated more severe disease. FAS included all subjects who received at least 1 dose of study medication in this study. NRI method was used for missing data except for visits after a subject advanced to other studies where LOCF method was used.

End point type

Secondary

End point timeframe

Months 2, 12, 24 and 36

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects
Month 2	132	191
Month 12	129	282
Month 24	104	266
Month 36	107	260

No statistical analyses for this end point

Secondary: Number of Subjects in Partial Mayo Score (PMS) Remission at Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84: Observed Cases

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End point title

Number of Subjects in Partial Mayo Score (PMS) Remission at Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84: Observed Cases

End point description

PMS was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 sub scores: stool frequency, rectal bleeding and PGA, each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total score range of 0 to 9, where higher score indicated more severe disease. PMS remission was defined as a partial Mayo score <=2 with no individual sub score >1. Here, "Number of subjects analysed" signifies subjects evaluable for this endpoint and "n" signifies subjects evaluable at each specified timepoint. Data is presented for observed cases, no imputation technique was applied. Here, 99999 indicated data could not be reported as no subjects were evaluable at that time point.

End point type

Secondary

End point timeframe

Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	166	729
Units: subjects
Month 1 (n= 165, 729)	158	275
Month 4 (n= 165, 532)	152	375
Month 6 (n= 166, 505)	155	395
Month 9 (n= 160, 469)	154	390
Month 15 (n= 145, 418)	139	361
Month 18 (n= 144, 404)	137	354
Month 21 (n= 138, 394)	125	351
Month 27 (n= 125, 348)	117	319
Month 30 (n= 124, 338)	117	307
Month 33 (n= 118, 326)	111	304
Month 39 (n= 105, 281)	102	261
Month 42 (n= 100, 253)	95	236
Month 45 (n= 102, 226)	95	212
Month 48 (n= 92, 199)	87	183
Month 51 (n= 89, 175)	87	162
Month 54 (n= 71, 147)	68	140
Month 57 (n= 56, 128)	54	120
Month 60 (n= 39, 107)	38	98
Month 63 (n= 28, 89)	28	80
Month 66 (n= 89, 175)	19	67
Month 69 (n= 11, 54)	10	49
Month 72 (n= 6, 44)	6	40
Month 75 (n= 3, 26)	3	24
Month 78 (n= 4, 19)	4	18
Month 81 (n= 0, 11)	99999	10
Month 84 (n= 0, 8)	99999	6

No statistical analyses for this end point

Secondary: Number of Subjects in Partial Mayo Score (PMS) Remission at Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

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End point title

Number of Subjects in Partial Mayo Score (PMS) Remission at Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

End point description

PMS was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 sub scores: stool frequency, rectal bleeding and PGA, each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total score range of 0 to 9, where higher score indicated more severe disease. PMS remission was defined as a partial Mayo score <=2 with no individual sub score >1. FAS included all subjects who received at least 1 dose of study medication in this study. Here, "n" signifies subjects evaluable at each specified time point. NRI method was used for missing data at all visits except for visits after a participant advanced to other studies and would reach the visits if the subject stayed in the study where LOCF method was used.

End point type

Secondary

End point timeframe

Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects
Month 1 (n= 175, 769)	158	275
Month 4 (n= 175, 769)	152	375
Month 6 (n= 175, 769)	155	395
Month 9 (n= 175, 769)	154	390
Month 15 (n= 175, 769)	139	361
Month 18 (n= 175, 769)	137	354
Month 21 (n= 175, 769)	125	351
Month 27 (n= 175, 769)	117	325
Month 30 (n= 175, 769)	117	316
Month 33 (n= 175, 769)	114	317
Month 39 (n= 175, 769)	108	293
Month 42 (n= 175, 769)	102	286
Month 45 (n= 175, 769)	102	283
Month 48 (n= 175, 769)	95	274
Month 51 (n= 175, 769)	96	267
Month 54 (n= 170, 764)	76	250
Month 57 (n= 160, 753)	61	234
Month 60 (n= 149, 732)	44	213
Month 63 (n= 135, 707)	31	194
Month 66 (n= 125, 659)	22	168
Month 69 (n= 114, 562)	13	131
Month 72 (n= 109, 468)	7	102
Month 75 (n= 102, 412)	3	73
Month 78 (n= 96, 339)	4	52
Month 81 (n= 95, 284)	0	29
Month 84 (n= 91, 210)	0	15

No statistical analyses for this end point

Secondary: Number of Subjects who Achieved Mucosal Healing at Months 2, 12, 24 and 36: Observed Cases

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End point title

Number of Subjects who Achieved Mucosal Healing at Months 2, 12, 24 and 36: Observed Cases

End point description

Mucosal healing in subjects was defined as mayo endoscopic sub score of 0 or 1. The mayo endoscopic sub score consisted of the findings of flexible sigmoidoscopy, graded from 0 to 3 with higher sub scores indicated higher disease severity. FAS included all subjects who received at least 1 dose of study medication in this study. Here, "Number of subjects analysed" signifies subjects evaluable for this endpoint and "n" signifies subjects evaluable at each specified time point. Data is presented for observed cases, no imputation technique was applied.

End point type

Secondary

End point timeframe

Months 2, 12, 24 and 36

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	169	690
Units: subjects
Month 2 (n= 169, 690)	152	279
Month 12 (n= 156, 458)	140	340
Month 24 (n= 136, 382)	119	307
Month 36 (n= 115, 307)	107	265

No statistical analyses for this end point

Secondary: Number of Subjects who Achieved Mucosal Healing at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

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End point title

Number of Subjects who Achieved Mucosal Healing at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

End point description

Mucosal healing in subjects was defined as mayo endoscopic sub score of 0 or 1. The mayo endoscopic sub score consisted of the findings of flexible sigmoidoscopy, graded from 0 to 3 with higher sub scores indicating higher disease severity. FAS included all subjects who received at least 1 dose of study medication in this study. NRI method was used for missing data at all visits and LOCF method was used for visits after a subject advanced to next study.

End point type

Secondary

End point timeframe

Months 2, 12, 24 and 36

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects
Month 2	152	279
Month 12	140	340
Month 24	119	307
Month 36	113	285

No statistical analyses for this end point

Secondary: Number of Subjects With Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score >=170 at Months 2, 6, 12, 18, 24, 30, 36, 48, 60, 72 and 84: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

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End point title

Number of Subjects With Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score >=170 at Months 2, 6, 12, 18, 24, 30, 36, 48, 60, 72 and 84: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF)

End point description

IBDQ was a psychometrically validated patient reported outcome (PRO) instrument for measuring the disease-specific quality of life in subjects with inflammatory bowel disease (IBD), including ulcerative colitis consisted of 32 items scored from 1 (worst response) to 7 (best response). For each domain, higher score indicates better quality of life (QOL). Total score was the sum of each item score, and ranged from 32 to 224 with a higher score indicated better QOL. FAS included all subjects who received at least 1 dose of study medication in this study. Here, "n" signifies subjects evaluable at each specified time point. NRI method was used for missing data at all visits except for visits after a subject advanced to other studies and would reach the visits if the subject stayed in the study where LOCF method was used.

End point type

Secondary

End point timeframe

Months 2, 6, 12, 18, 24, 30, 36, 48, 60, 72 and 84

End point values	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Number of subjects analysed	175	769
Units: subjects
Month 2 (n= 175, 769)	154	419
Month 6 (n= 175, 769)	151	395
Month 12 (n= 175, 769)	140	365
Month 18 (n= 175, 769)	123	354
Month 24 (n= 175, 769)	120	315
Month 30 (n= 175, 769)	115	299
Month 36 (n= 175, 769)	111	294
Month 48 (n= 175, 769)	93	265
Month 60 (n= 149, 732)	45	215
Month 72 (n= 109, 468)	8	99
Month 84 (n= 91, 210)	0	14

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group)

Adverse event reporting additional description

Same event may appear as both an AE and 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. Analysis performed on safety analysis set.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Subjects who completed Study A3921096 and were in remission at Week 52 of Study A3921096, received Tofacitinib 5 milligram (mg) tablets twice daily (BID) for maximum of 80 months in this Study A3921139. Remission was defined as total Mayo score <=2 with no individual sub score >1 and rectal bleeding sub score of 0.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Subjects who had completed Study A3921096 and not in remission, or who had early withdrawal due to treatment failure from Study A3921096, or who were non responders after completing A3921094 or A3921095 received Tofacitinib 10 mg tablets twice daily for maximum of 84 months in this Study A3921139.

Serious adverse events	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Total subjects affected by serious adverse events
subjects affected / exposed	39 / 175 (22.29%)	147 / 769 (19.12%)
number of deaths (all causes)	0	6
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Adenocarcinoma metastatic
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Adenocarcinoma of colon
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Adenoma benign
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	2 / 175 (1.14%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	2 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	2 / 175 (1.14%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	1 / 175 (0.57%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colon adenoma
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Colorectal cancer metastatic
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diffuse large B-cell lymphoma
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Epstein-Barr virus associated lymphoma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fibroadenoma of breast
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic angiosarcoma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Invasive ductal breast carcinoma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leiomyosarcoma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung neoplasm
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
Meningioma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to liver
subjects affected / exposed	1 / 175 (0.57%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to lymph nodes
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to peritoneum
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal adenocarcinoma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest discomfort
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
subjects affected / exposed	1 / 175 (0.57%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical dysplasia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervix haemorrhage uterine
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal polyps
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 175 (0.00%)	5 / 769 (0.65%)
occurrences causally related to treatment / all	0 / 0	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 1
Pulmonary mass
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Major depression
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Product issues
Device loosening
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (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
Alcohol poisoning
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	1 / 175 (0.57%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Clavicle fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	2 / 175 (1.14%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	2 / 175 (1.14%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ligament sprain
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle strain
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	1 / 175 (0.57%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block second degree
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Cardiac failure
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebellar haemorrhage
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical radiculopathy
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post herpetic neuralgia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vertebrobasilar insufficiency
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Deafness unilateral
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vertigo
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diplopia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anal skin tags
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	4 / 175 (2.29%)	38 / 769 (4.94%)
occurrences causally related to treatment / all	0 / 4	4 / 39
deaths causally related to treatment / all	0 / 0	0 / 0
Colon dysplasia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspepsia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Frequent bowel movements
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal perforation
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
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 / 175 (0.57%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
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	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Megacolon
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Proctalgia
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Proctitis
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis chronic
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acne conglobata
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis contact
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eosinophilic pustular folliculitis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Erythema nodosum
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Calculus urinary
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 175 (0.57%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Prerenal failure
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ureteric obstruction
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Hyperparathyroidism
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thyroid mass
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis reactive
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 175 (0.57%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Femoroacetabular impingement
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neck pain
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal pain
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Synovitis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 175 (0.00%)	3 / 769 (0.39%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial vaginosis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis staphylococcal
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Complicated appendicitis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cytomegalovirus hepatitis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis infectious
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis norovirus
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	1 / 175 (0.57%)	4 / 769 (0.52%)
occurrences causally related to treatment / all	1 / 1	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster meningitis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Histoplasmosis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis viral
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Necrotising fasciitis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ophthalmic herpes zoster
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pilonidal cyst
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary mycosis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 175 (0.00%)	2 / 769 (0.26%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 175 (0.57%)	0 / 769 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 175 (0.00%)	1 / 769 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Total subjects affected by non serious adverse events
subjects affected / exposed	134 / 175 (76.57%)	550 / 769 (71.52%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	4 / 175 (2.29%)	14 / 769 (1.82%)
occurrences all number	4	15
Vascular disorders
Hypertension
subjects affected / exposed	17 / 175 (9.71%)	28 / 769 (3.64%)
occurrences all number	18	31
General disorders and administration site conditions
Fatigue
subjects affected / exposed	5 / 175 (2.86%)	33 / 769 (4.29%)
occurrences all number	6	37
Oedema peripheral
subjects affected / exposed	4 / 175 (2.29%)	13 / 769 (1.69%)
occurrences all number	4	14
Pyrexia
subjects affected / exposed	2 / 175 (1.14%)	25 / 769 (3.25%)
occurrences all number	2	28
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	14 / 175 (8.00%)	38 / 769 (4.94%)
occurrences all number	19	41
Dyspnoea
subjects affected / exposed	5 / 175 (2.86%)	7 / 769 (0.91%)
occurrences all number	5	8
Rhinorrhoea
subjects affected / exposed	4 / 175 (2.29%)	4 / 769 (0.52%)
occurrences all number	4	4
Psychiatric disorders
Anxiety
subjects affected / exposed	6 / 175 (3.43%)	16 / 769 (2.08%)
occurrences all number	6	16
Depression
subjects affected / exposed	4 / 175 (2.29%)	12 / 769 (1.56%)
occurrences all number	5	12
Insomnia
subjects affected / exposed	5 / 175 (2.86%)	18 / 769 (2.34%)
occurrences all number	5	19
Investigations
Alanine aminotransferase increased
subjects affected / exposed	6 / 175 (3.43%)	11 / 769 (1.43%)
occurrences all number	6	11
Aspartate aminotransferase increased
subjects affected / exposed	5 / 175 (2.86%)	8 / 769 (1.04%)
occurrences all number	5	8
Blood cholesterol increased
subjects affected / exposed	7 / 175 (4.00%)	18 / 769 (2.34%)
occurrences all number	7	20
Blood creatine phosphokinase increased
subjects affected / exposed	19 / 175 (10.86%)	85 / 769 (11.05%)
occurrences all number	22	108
Lymphocyte count decreased
subjects affected / exposed	3 / 175 (1.71%)	18 / 769 (2.34%)
occurrences all number	7	24
White blood cell count decreased
subjects affected / exposed	4 / 175 (2.29%)	8 / 769 (1.04%)
occurrences all number	5	9
Injury, poisoning and procedural complications
Ligament sprain
subjects affected / exposed	4 / 175 (2.29%)	8 / 769 (1.04%)
occurrences all number	4	8
Skin laceration
subjects affected / exposed	5 / 175 (2.86%)	4 / 769 (0.52%)
occurrences all number	5	4
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 175 (2.29%)	14 / 769 (1.82%)
occurrences all number	4	15
Headache
subjects affected / exposed	12 / 175 (6.86%)	57 / 769 (7.41%)
occurrences all number	23	81
Paraesthesia
subjects affected / exposed	2 / 175 (1.14%)	17 / 769 (2.21%)
occurrences all number	2	17
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 175 (1.71%)	36 / 769 (4.68%)
occurrences all number	4	38
Lymphopenia
subjects affected / exposed	6 / 175 (3.43%)	13 / 769 (1.69%)
occurrences all number	9	23
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	6 / 175 (3.43%)	47 / 769 (6.11%)
occurrences all number	8	54
Abdominal pain upper
subjects affected / exposed	4 / 175 (2.29%)	24 / 769 (3.12%)
occurrences all number	8	33
Colitis ulcerative
subjects affected / exposed	44 / 175 (25.14%)	131 / 769 (17.04%)
occurrences all number	57	150
Constipation
subjects affected / exposed	7 / 175 (4.00%)	20 / 769 (2.60%)
occurrences all number	7	20
Diarrhoea
subjects affected / exposed	9 / 175 (5.14%)	34 / 769 (4.42%)
occurrences all number	11	38
Dyspepsia
subjects affected / exposed	8 / 175 (4.57%)	12 / 769 (1.56%)
occurrences all number	9	12
Gastrooesophageal reflux disease
subjects affected / exposed	10 / 175 (5.71%)	15 / 769 (1.95%)
occurrences all number	11	15
Haemorrhoids
subjects affected / exposed	3 / 175 (1.71%)	20 / 769 (2.60%)
occurrences all number	3	21
Nausea
subjects affected / exposed	1 / 175 (0.57%)	30 / 769 (3.90%)
occurrences all number	1	37
Vomiting
subjects affected / exposed	3 / 175 (1.71%)	20 / 769 (2.60%)
occurrences all number	3	23
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	5 / 175 (2.86%)	20 / 769 (2.60%)
occurrences all number	5	22
Rash
subjects affected / exposed	4 / 175 (2.29%)	38 / 769 (4.94%)
occurrences all number	4	41
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	17 / 175 (9.71%)	76 / 769 (9.88%)
occurrences all number	22	96
Back pain
subjects affected / exposed	11 / 175 (6.29%)	28 / 769 (3.64%)
occurrences all number	16	31
Musculoskeletal pain
subjects affected / exposed	2 / 175 (1.14%)	18 / 769 (2.34%)
occurrences all number	2	24
Myalgia
subjects affected / exposed	6 / 175 (3.43%)	10 / 769 (1.30%)
occurrences all number	6	12
Osteoarthritis
subjects affected / exposed	6 / 175 (3.43%)	9 / 769 (1.17%)
occurrences all number	6	10
Tendonitis
subjects affected / exposed	5 / 175 (2.86%)	4 / 769 (0.52%)
occurrences all number	5	4
Infections and infestations
Bronchitis
subjects affected / exposed	17 / 175 (9.71%)	30 / 769 (3.90%)
occurrences all number	26	44
Ear infection
subjects affected / exposed	4 / 175 (2.29%)	6 / 769 (0.78%)
occurrences all number	4	6
Gastroenteritis
subjects affected / exposed	12 / 175 (6.86%)	51 / 769 (6.63%)
occurrences all number	15	60
Herpes zoster
subjects affected / exposed	12 / 175 (6.86%)	50 / 769 (6.50%)
occurrences all number	13	52
Influenza
subjects affected / exposed	23 / 175 (13.14%)	63 / 769 (8.19%)
occurrences all number	32	76
Latent tuberculosis
subjects affected / exposed	4 / 175 (2.29%)	13 / 769 (1.69%)
occurrences all number	4	13
Oral herpes
subjects affected / exposed	1 / 175 (0.57%)	18 / 769 (2.34%)
occurrences all number	3	42
Nasopharyngitis
subjects affected / exposed	41 / 175 (23.43%)	157 / 769 (20.42%)
occurrences all number	91	302
Pharyngitis
subjects affected / exposed	8 / 175 (4.57%)	14 / 769 (1.82%)
occurrences all number	8	16
Pneumonia
subjects affected / exposed	4 / 175 (2.29%)	9 / 769 (1.17%)
occurrences all number	5	9
Sinusitis
subjects affected / exposed	8 / 175 (4.57%)	25 / 769 (3.25%)
occurrences all number	13	30
Rhinitis
subjects affected / exposed	5 / 175 (2.86%)	7 / 769 (0.91%)
occurrences all number	5	8
Upper respiratory tract infection
subjects affected / exposed	19 / 175 (10.86%)	77 / 769 (10.01%)
occurrences all number	27	114
Urinary tract infection
subjects affected / exposed	13 / 175 (7.43%)	34 / 769 (4.42%)
occurrences all number	20	60
Viral upper respiratory tract infection
subjects affected / exposed	5 / 175 (2.86%)	7 / 769 (0.91%)
occurrences all number	5	7
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	1 / 175 (0.57%)	38 / 769 (4.94%)
occurrences all number	1	43
Hyperlipidaemia
subjects affected / exposed	4 / 175 (2.29%)	10 / 769 (1.30%)
occurrences all number	4	10

More information

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Were there any global substantial amendments to the protocol? Yes

22 Oct 2018

This amendment specified the end of the trial will be approximately in July 2020. This 2 year extension of the study allowed for additional collection of long term safety and efficacy data in UC patients on tofacitinib.

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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