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Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects with Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD) - SELECT - PsA 1

Summary
EudraCT number	2016-004130-24
Trial protocol	SK BE DE CZ GB GR NL PT EE LV LT SI HU ES HR BG IT
Global end of trial date	09 Sep 2024

Results information
Results version number	v1(current)
This version publication date	23 Oct 2025
First version publication date	23 Oct 2025
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

M15-572

ISRCTN number

US NCT number

NCT03104400

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4UB

Public contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Scientific contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.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

09 Sep 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Sep 2024

Was the trial ended prematurely?

Main objective of the trial

This study includes two periods. The main objective of Period 1 is to compare the efficacy of upadacitinib 15 mg once daily (QD) and 30 mg QD versus placebo and versus adalimumab (Humira®) in participants with moderately to severely active psoriatic arthritis (PsA) who have had an inadequate response to non-biologic DMARDs (DMARD-IR). Period 1 is also designed to compare the efficacy of upadacitinib 15 mg and 30 mg QD versus placebo for the prevention of structural progression. The objective of Period 2 is to evaluate the long-term safety, tolerability and efficacy of upadacitinib 15 mg and 30 mg QD in participants who have completed Period 1. The study includes a 35-day screening period, a 56-week blinded period (Period 1), a long-term extension period of up to a total treatment duration of approximately 5 years (Period 2), a 30-day follow-up call or visit, and a 70-day follow-up call.

Protection of trial subjects

Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. For subjects in Japan only: if a subject is under 20 years of age, then the subject and their parent or legal guardian must voluntarily sign and date an informed consent.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Apr 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 15

Country: Number of subjects enrolled

Argentina: 50

Country: Number of subjects enrolled

Belarus: 15

Country: Number of subjects enrolled

Belgium: 7

Country: Number of subjects enrolled

Bosnia and Herzegovina: 12

Country: Number of subjects enrolled

Brazil: 50

Country: Number of subjects enrolled

Bulgaria: 83

Country: Number of subjects enrolled

Canada: 39

Country: Number of subjects enrolled

Chile: 45

Country: Number of subjects enrolled

Colombia: 16

Country: Number of subjects enrolled

Estonia: 23

Country: Number of subjects enrolled

Greece: 9

Country: Number of subjects enrolled

Hong Kong: 11

Country: Number of subjects enrolled

Hungary: 78

Country: Number of subjects enrolled

Ireland: 1

Country: Number of subjects enrolled

Italy: 15

Country: Number of subjects enrolled

Japan: 15

Country: Number of subjects enrolled

Lithuania: 23

Country: Number of subjects enrolled

Malaysia: 10

Country: Number of subjects enrolled

Netherlands: 9

Country: Number of subjects enrolled

New Zealand: 36

Country: Number of subjects enrolled

Poland: 170

Country: Number of subjects enrolled

Portugal: 21

Country: Number of subjects enrolled

Puerto Rico: 4

Country: Number of subjects enrolled

Russian Federation: 54

Country: Number of subjects enrolled

Slovakia: 39

Country: Number of subjects enrolled

Slovenia: 4

Country: Number of subjects enrolled

South Africa: 66

Country: Number of subjects enrolled

Korea, Republic of: 4

Country: Number of subjects enrolled

Spain: 15

Country: Number of subjects enrolled

Taiwan: 20

Country: Number of subjects enrolled

United Kingdom: 26

Country: Number of subjects enrolled

Ukraine: 134

Country: Number of subjects enrolled

United States: 261

Country: Number of subjects enrolled

Czechia: 52

Country: Number of subjects enrolled

Germany: 45

Country: Number of subjects enrolled

Israel: 12

Country: Number of subjects enrolled

China: 61

Country: Number of subjects enrolled

Croatia: 18

Country: Number of subjects enrolled

Latvia: 26

Country: Number of subjects enrolled

Mexico: 37

Country: Number of subjects enrolled

Serbia: 51

Country: Number of subjects enrolled

Singapore: 10

Country: Number of subjects enrolled

Switzerland: 2

Country: Number of subjects enrolled

Türkiye: 11

Worldwide total number of subjects

1705

EEA total number of subjects

638

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)

1468

From 65 to 84 years

237

85 years and over

Subject disposition

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Recruitment details

Screening details

The study included a 35-day Screening Period.

Period 1 title

Period 1 (Week 1 – 56)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo / Upadacitinib 15 mg

Arm description

Participants randomized to receive matching placebo to upadacitinib orally once a day (QD) for 24 weeks followed by upadacitinib 15 mg once daily for 32 weeks (Weeks 24 to 56), as well as matching placebo to adalimumab administered by subcutaneous injection every other week (EOW) from Weeks 1 to 56.

Arm type

Experimental

Investigational medicinal product name

Placebo to Upadacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Investigational medicinal product name

Placebo to Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Placebo / Upadacitinib 30 mg

Arm description

Participants randomized to receive matching placebo to upadacitinib orally QD for 24 weeks followed by upadacitinib 30 mg once daily for 32 weeks (Weeks 24 to 56), in addition to matching placebo to adalimumab administered by subcutaneous injection EOW from Weeks 1 to 56.

Arm type

Experimental

Investigational medicinal product name

Placebo to Upadacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Investigational medicinal product name

Placebo to Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Adalimumab 40 mg

Arm description

Participants randomized to receive adalimumab 40 mg by subcutaneous injection EOW and matching placebo to upadacitinib orally QD for 56 weeks.

Arm type

Experimental

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Humira®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Investigational medicinal product name

Placebo to Upadacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Upadacitinib 15 mg

Arm description

Participants randomized to receive upadacitinib 15 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Investigational medicinal product name

Placebo to Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Upadacitinib 30 mg

Arm description

Participants randomized to receive upadacitinib 30 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Investigational medicinal product name

Placebo to Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Number of subjects in period 1	Placebo / Upadacitinib 15 mg	Placebo / Upadacitinib 30 mg	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Started	211	212	429	430	423
Completed	177	178	370	379	366
Not completed	34	34	59	51	57
Adverse event, non-fatal	5	7	11	9	21
COVID-19 Logistical Restrictions	-	-	-	1	-
Other, not specified	2	3	7	6	4
Did not receive study drug	-	-	-	1	-
Lost to follow-up	4	1	4	8	7
Withdrawal by subject	17	20	29	24	24
Lack of efficacy	6	3	8	2	1

Period 2 title

Period 2 (Week 56 - 260)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo / Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Arm description

Participants randomized to receive matching placebo to upadacitinib orally once a day (QD) for 24 weeks followed by upadacitinib 15 mg orally once a day (QD) for 32 weeks (Weeks 24 to 56), as well as matching placebo to adalimumab administered by subcutaneous injection every other week (EOW) from Weeks 1 to 56 in Period 1. During Period 2 (Weeks 56 to 260) participants continued to receive upadacitinib 15 mg orally once a day (QD).

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Placebo / Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Arm description

Participants randomized to receive matching placebo to upadacitinib orally once a day (QD) for 24 weeks followed by upadacitinib 30 mg orally once a day (QD) for 32 weeks (Weeks 24 to 56), as well as matching placebo to adalimumab administered by subcutaneous injection every other week (EOW) from Weeks 1 to 56 in Period 1. During Period 2 (Weeks 56 to 260) participants continued to receive upadacitinib 30 mg orally once a day (QD).

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Adalimumab 40 mg Period 2 (Weeks 56 to 260)

Arm description

Participants randomized to receive adalimumab 40 mg by subcutaneous injection every other week (EOW) and matching placebo to upadacitinib orally once a day (QD) for 56 weeks in Period 1 who continued to receive 40 mg adalimumab EOW in Period 2 (Weeks 56 to 260).

Arm type

Experimental

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Humira®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered by subcutaneous injection

Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Arm description

Participants randomized to receive upadacitinib 15 mg orally once a day (QD) and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks in Period 1 who continued to receive 15 mg upadacitinib QD in Period 2 (Weeks 56 to 260).

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Arm description

Participants randomized to receive upadacitinib 30 mg orally once a day (QD) and matching placebo to adalimumab by subcutaneous injection every other week (EOW) for 56 weeks in Period 1 who continued to receive 30 mg upadacitinib QD in Period 2 (Weeks 56 to 260).

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT 494, RINVOQ®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablet

Number of subjects in period 2 ^[1]	Placebo / Upadacitinib 15 mg Period 2 (Weeks 56 to 260)	Placebo / Upadacitinib 30 mg Period 2 (Weeks 56 to 260)	Adalimumab 40 mg Period 2 (Weeks 56 to 260)	Upadacitinib 15 mg Period 2 (Weeks 56 to 260)	Upadacitinib 30 mg Period 2 (Weeks 56 to 260)
Started	177	178	366	378	365
Completed	131	121	268	272	269
Not completed	46	57	98	106	96
Adverse event, non-fatal	14	17	14	28	28
COVID-19 Logistical Restrictions	-	-	1	1	-
Other, not specified	10	7	17	12	18
Unknown	-	-	-	1	1
Lost to follow-up	7	6	12	12	7
COVID-19 infection	-	2	-	2	3
Withdrawal by subject	11	21	45	44	32
Lack of efficacy	4	4	9	6	7

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 1,470 subjects completed study Period 1, and 1,464 subjects entered study Period 2.

Baseline characteristics

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Reporting group title

Placebo / Upadacitinib 15 mg

Reporting group description

Reporting group title

Placebo / Upadacitinib 30 mg

Reporting group description

Reporting group title

Adalimumab 40 mg

Reporting group description

Participants randomized to receive adalimumab 40 mg by subcutaneous injection EOW and matching placebo to upadacitinib orally QD for 56 weeks.

Reporting group title

Upadacitinib 15 mg

Reporting group description

Participants randomized to receive upadacitinib 15 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks.

Reporting group title

Upadacitinib 30 mg

Reporting group description

Participants randomized to receive upadacitinib 30 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks.

Reporting group values	Placebo / Upadacitinib 15 mg	Placebo / Upadacitinib 30 mg	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg	Total
Number of subjects	211	212	429	430	423	1705
Age categorical
Units: Subjects
< 65 years	185	182	362	368	371	1468
65 - < 75 years	24	28	61	52	46	211
≥75 years	2	2	6	10	6	26
Age continuous
Units: years
arithmetic mean (standard deviation)	50.0 ( 12.25 )	50.8 ( 12.18 )	51.4 ( 12.04 )	51.6 ( 12.18 )	49.9 ( 12.41 )	-
Gender categorical
Units: Subjects
Female	98	113	222	239	236	908
Male	113	99	207	191	187	797
Ethnicity
Units: Subjects
Hispanic or Latino	29	37	65	60	53	244
Not Hispanic or Latino	182	175	364	370	370	1461
Unknown or Not Reported	0	0	0	0	0	0
Race/Ethnicity
Units: Subjects
White	190	187	375	387	377	1516
Black or African American	2	1	2	1	3	9
American Indian/ Alaska Native	1	1	2	0	2	6
Native Hawaiian or other Pacific Islander	0	1	2	0	1	4
Asian	16	21	41	37	34	149
Multiple	2	1	7	5	6	21
Extent of Psoriasis
The extent of psoriasis was measured by the physician as the total body surface area (BSA) involved with psoriasis. For purposes of clinical estimation, the total surface of the participant's palm and five digits was assumed to be approximately equivalent to 1% of BSA.
Units: Subjects
< 3% BSA	108	104	218	215	213	858
≥3% BSA	103	108	211	214	210	846
Missing	0	0	0	1	0	1
Current Use of at Least 1 Non- Biologic DMARD
Units: Subjects
Yes	174	173	346	353	345	1391
No	37	39	83	77	78	314
Presence of Dactylitis
Dactylitis is characterized by swelling of the fingers or toes. The Leeds dactylitis index (LDI) is a score based on finger circumference and tenderness, assessed across all digits. The presence of a dactylitic digit is defined as at least 1 affected AND tender digit with circumference increase over reference digit ≥10%. Digit scores are calculated from the ratio of circumference between an affected digit and control digit and the tenderness score; unaffected digits have score = 0. Scores from each digit are summed to provide the final LDI. The presence of dactylitis is defined as LDI > 0.
Units: Subjects
Yes	65	61	127	136	127	516
No	146	151	302	293	296	1188
Missing	0	0	0	1	0	1
Presence of Enthesitis
Enthesitis is inflammation of the entheses, the specific point where tendons or ligaments attach to bone. Tenderness at 9 bilateral sites was assessed as present (1) or absent (0). The total enthesitis count is calculated by summing the tenderness scores from all 18 sites (range 0 - 18). Presence of enthesitis is defined as Total Enthesitis Count > 0.
Units: Subjects
Yes	161	161	331	333	331	1317
No	50	51	98	96	92	387
Missing	0	0	0	1	0	1
Duration of Psoriatic Arthritis Symptoms
Analysis Population Description: Participants with available data Number of participants analyzed = 428 for the Adalimumab 40 mg group and 429 for the Upadacitinib 15 mg group
Units: years
arithmetic mean (standard deviation)	9.6 ( 9.00 )	9.0 ( 8.15 )	9.1 ( 8.78 )	9.2 ( 8.63 )	9.2 ( 8.28 )	-
Duration of PsA Diagnosis
Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: years
arithmetic mean (standard deviation)	6.4 ( 7.39 )	6.1 ( 6.63 )	5.9 ( 7.06 )	6.2 ( 7.41 )	5.9 ( 6.37 )	-
Tender Joint Count (TJC)
A total of 68 joints were assessed for the presence or absence of tenderness. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: joints
arithmetic mean (standard deviation)	20.7 ( 15.67 )	19.3 ( 12.89 )	20.1 ( 13.82 )	20.4 ( 14.72 )	19.4 ( 13.32 )	-
Swollen Joint Count (SJC)
A total of 66 joints were assessed for the presence or absence of swelling. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: joints
arithmetic mean (standard deviation)	11.4 ( 8.47 )	10.7 ( 7.85 )	11.6 ( 8.75 )	11.6 ( 9.31 )	10.6 ( 7.06 )	-
Patient's Assessment of Pain
Participants were asked to indicate the severity of their arthritis pain within the previous week on a numeric rating scale (NRS) from 0 to 10. A score of 0 indicates "no pain" and a score of 10 indicates "worst possible pain." Analysis Population Description: Participants with available data; Placebo / Upadacitinib 30 mg (n=210); Adalimumab 40 mg (n=428); Upadacitinib 15 mg (n=425); Upadacitinib 30 mg (n=421)
Units: units on a scale
arithmetic mean (standard deviation)	6.0 ( 2.21 )	6.2 ( 2.07 )	6.0 ( 2.08 )	6.2 ( 2.07 )	5.9 ( 2.05 )	-
Patient's Global Assessment of Disease Activity
The participant was asked to rate their current psoriatic arthritis disease activity on a 0 to 10 NRS, where 0 indicates very low disease activity and 10 indicates very high disease activity. Analysis Population Description: Participants with available data; Placebo / Upadacitinib 30 mg (n=210); Adalimumab 40 mg (n=428); Upadacitinib 15 mg (n=425); Upadacitinib 30 mg (n=421)
Units: units on a scale
arithmetic mean (standard deviation)	6.2 ( 2.17 )	6.4 ( 1.89 )	6.3 ( 2.03 )	6.6 ( 2.03 )	6.4 ( 2.07 )	-
Physician's Global Assessment of Disease Activity
The physician rated the participant's current global psoriatic arthritis disease activity (independently from the participant's assessment) on a 0 to 10 NRS where 0 indicates very low disease activity and 10 indicates very high disease activity. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: units on a scale
arithmetic mean (standard deviation)	6.6 ( 1.65 )	6.4 ( 1.62 )	6.6 ( 1.65 )	6.7 ( 1.62 )	6.5 ( 1.68 )	-
Health Assessment Questionnaire - Disability Index (HAQ-DI)
HAQ DI is a patient-reported questionnaire measuring difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Subjects assessed ability to do each task on a scale from 0 to 3). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 = no disability and 3= very severe, high-dependency disability. Analysis Population: Subjects w/available data; Pbo / Upa 30 mg (n=210); Adalimumab 40 mg (n=428); Upadacitinib 15 mg (n=425); Upadacitinib 30 mg (n=421)
Units: units on a scale
arithmetic mean (standard deviation)	1.08 ( 0.638 )	1.15 ( 0.640 )	1.12 ( 0.626 )	1.15 ( 0.653 )	1.09 ( 0.630 )	-
High-sensitivity C- reactive Protein (hsCRP)
C-reactive protein (CRP) is a protein found in blood. CRP levels rise in response to inflammation. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: mg/mL
arithmetic mean (standard deviation)	12.00 ( 17.146 )	10.96 ( 14.357 )	10.91 ( 15.462 )	11.00 ( 14.910 )	11.49 ( 15.355 )	-

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab by subcutaneous (SC) injection EOW.

Subject analysis set title

Adalimumab 40 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD.

Subject analysis set title

Upadacitinib 15 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW.

Subject analysis set title

Upadacitinib 30 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW.

Subject analysis sets values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects	423	429	429	423
Age categorical
Units: Subjects
< 65 years	367	362	367	371
65 - < 75 years	52	61	52	46
≥75 years	4	6	10	6
Age continuous
Units: years
arithmetic mean (standard deviation)	50.4 ( 12.21 )	51.4 ( 12.04 )	51.6 ( 12.19 )	49.9 ( 12.41 )
Gender categorical
Units: Subjects
Female	211	222	238	236
Male	212	207	191	187
Ethnicity
Units: Subjects
Hispanic or Latino	66	65	59	53
Not Hispanic or Latino	357	364	370	370
Unknown or Not Reported	0	0	0	0
Race/Ethnicity
Units: Subjects
White	377	375	386	377
Black or African American	3	2	1	3
American Indian/ Alaska Native	2	2	0	2
Native Hawaiian or other Pacific Islander	1	2	0	1
Asian	37	41	37	34
Multiple	3	7	5	6
Extent of Psoriasis
The extent of psoriasis was measured by the physician as the total body surface area (BSA) involved with psoriasis. For purposes of clinical estimation, the total surface of the participant's palm and five digits was assumed to be approximately equivalent to 1% of BSA.
Units: Subjects
< 3% BSA	212	218	215	213
≥3% BSA	211	211	214	210
Missing	0	0	0	0
Current Use of at Least 1 Non- Biologic DMARD
Units: Subjects
Yes	347	347	353	346
No	76	82	76	77
Presence of Dactylitis
Dactylitis is characterized by swelling of the fingers or toes. The Leeds dactylitis index (LDI) is a score based on finger circumference and tenderness, assessed across all digits. The presence of a dactylitic digit is defined as at least 1 affected AND tender digit with circumference increase over reference digit ≥10%. Digit scores are calculated from the ratio of circumference between an affected digit and control digit and the tenderness score; unaffected digits have score = 0. Scores from each digit are summed to provide the final LDI. The presence of dactylitis is defined as LDI > 0.
Units: Subjects
Yes	126	127	136	127
No	297	302	293	296
Missing	0	0	0	0
Presence of Enthesitis
Enthesitis is inflammation of the entheses, the specific point where tendons or ligaments attach to bone. Tenderness at 9 bilateral sites was assessed as present (1) or absent (0). The total enthesitis count is calculated by summing the tenderness scores from all 18 sites (range 0 - 18). Presence of enthesitis is defined as Total Enthesitis Count > 0.
Units: Subjects
Yes	322	330	333	331
No	101	99	96	92
Missing	0	0	0	0
Duration of Psoriatic Arthritis Symptoms
Analysis Population Description: Participants with available data Number of participants analyzed = 428 for the Adalimumab 40 mg group and 429 for the Upadacitinib 15 mg group
Units: years
arithmetic mean (standard deviation)	9.3 ( 8.58 )	9.1 ( 8.78 )	9.2 ( 8.63 )	9.2 ( 8.28 )
Duration of PsA Diagnosis
Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: years
arithmetic mean (standard deviation)	6.2 ( 7.01 )	5.9 ( 7.06 )	6.2 ( 7.41 )	5.9 ( 6.37 )
Tender Joint Count (TJC)
A total of 68 joints were assessed for the presence or absence of tenderness. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: joints
arithmetic mean (standard deviation)	20.0 ( 14.34 )	20.1 ( 13.82 )	20.4 ( 14.72 )	19.4 ( 13.32 )
Swollen Joint Count (SJC)
A total of 66 joints were assessed for the presence or absence of swelling. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: joints
arithmetic mean (standard deviation)	11.0 ( 8.16 )	11.6 ( 8.75 )	11.6 ( 9.31 )	10.6 ( 7.06 )
Patient's Assessment of Pain
Participants were asked to indicate the severity of their arthritis pain within the previous week on a numeric rating scale (NRS) from 0 to 10. A score of 0 indicates "no pain" and a score of 10 indicates "worst possible pain." Analysis Population Description: Participants with available data; Placebo / Upadacitinib 30 mg (n=210); Adalimumab 40 mg (n=428); Upadacitinib 15 mg (n=425); Upadacitinib 30 mg (n=421)
Units: units on a scale
arithmetic mean (standard deviation)	6.1 ( 2.04 )	6.0 ( 2.08 )	6.2 ( 2.07 )	5.9 ( 2.05 )
Patient's Global Assessment of Disease Activity
The participant was asked to rate their current psoriatic arthritis disease activity on a 0 to 10 NRS, where 0 indicates very low disease activity and 10 indicates very high disease activity. Analysis Population Description: Participants with available data; Placebo / Upadacitinib 30 mg (n=210); Adalimumab 40 mg (n=428); Upadacitinib 15 mg (n=425); Upadacitinib 30 mg (n=421)
Units: units on a scale
arithmetic mean (standard deviation)	6.3 ( 2.04 )	6.3 ( 2.03 )	6.6 ( 2.03 )	6.4 ( 2.07 )
Physician's Global Assessment of Disease Activity
The physician rated the participant's current global psoriatic arthritis disease activity (independently from the participant's assessment) on a 0 to 10 NRS where 0 indicates very low disease activity and 10 indicates very high disease activity. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: units on a scale
arithmetic mean (standard deviation)	6.5 ( 1.64 )	6.6 ( 1.65 )	6.7 ( 1.62 )	6.5 ( 1.68 )
Health Assessment Questionnaire - Disability Index (HAQ-DI)
HAQ DI is a patient-reported questionnaire measuring difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Subjects assessed ability to do each task on a scale from 0 to 3). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 = no disability and 3= very severe, high-dependency disability. Analysis Population: Subjects w/available data; Pbo / Upa 30 mg (n=210); Adalimumab 40 mg (n=428); Upadacitinib 15 mg (n=425); Upadacitinib 30 mg (n=421)
Units: units on a scale
arithmetic mean (standard deviation)	1.12 ( 0.639 )	1.12 ( 0.626 )	1.15 ( 0.653 )	1.09 ( 0.630 )
High-sensitivity C- reactive Protein (hsCRP)
C-reactive protein (CRP) is a protein found in blood. CRP levels rise in response to inflammation. Analysis Population Description: Participants with available data Number of participants analyzed = 429 for the Upadacitinib 15 mg group
Units: mg/mL
arithmetic mean (standard deviation)	11.48 ( 15.800 )	10.91 ( 15.462 )	11.00 ( 14.910 )	11.49 ( 15.355 )

End points

Top of page

Reporting group title

Placebo / Upadacitinib 15 mg

Reporting group description

Reporting group title

Placebo / Upadacitinib 30 mg

Reporting group description

Reporting group title

Adalimumab 40 mg

Reporting group description

Participants randomized to receive adalimumab 40 mg by subcutaneous injection EOW and matching placebo to upadacitinib orally QD for 56 weeks.

Reporting group title

Upadacitinib 15 mg

Reporting group description

Participants randomized to receive upadacitinib 15 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks.

Reporting group title

Upadacitinib 30 mg

Reporting group description

Participants randomized to receive upadacitinib 30 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks.

Reporting group title

Placebo / Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Placebo / Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Adalimumab 40 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Reporting group description

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab by subcutaneous (SC) injection EOW.

Subject analysis set title

Adalimumab 40 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD.

Subject analysis set title

Upadacitinib 15 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW.

Subject analysis set title

Upadacitinib 30 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW.

Primary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

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End point title

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

End point description

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: 1. ≥20% improvement in 68-tender joint count; 2. ≥20% improvement in 66-swollen joint count; and 3. ≥20% improvement in at least 3 of the 5 following parameters: •Physician global assessment of disease activity •Patient global assessment of disease activity •Patient assessment of pain •Health Assessment Questionnaire - Disability Index (HAQ-DI) •High-sensitivity C-reactive protein (hsCRP). Analysis population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.

End point type

Primary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	423	429	429	423
Units: percentage of participants
number (confidence interval 95%)	36.2 (31.6 to 40.7)	65.0 (60.5 to 69.5)	70.6 (66.3 to 74.9)	78.5 (74.6 to 82.4)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified αtransfer path.

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

34.5

Confidence interval

level

95%

sides

2-sided

lower limit

28.2

upper limit

40.7

Notes
[1] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Upadacitinib 30 mg v Placebo

Number of subjects included in analysis

846

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

42.3

Confidence interval

level

95%

sides

2-sided

lower limit

36.3

upper limit

48.3

Notes
[2] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

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End point title

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

End point description

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement. Analysis popualation: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	392	406	404	398
Units: units on a scale
least squares mean (confidence interval 95%)	-0.14 (-0.18 to -0.09)	-0.34 (-0.38 to -0.29)	-0.42 (-0.47 to -0.37)	-0.47 (-0.52 to -0.42)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

796

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[3]

Method

[Mixed Effect Model Repeated Measurement

Parameter type

[Least Squares (LS) Mean Difference

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

-0.22

Notes
[3] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

790

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[4]

Method

[Mixed Effect Model Repeated Measurement

Parameter type

[Least Squares (LS) Mean Difference

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.27

Notes
[4] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16

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End point title

Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16

End point description

The sIGA is a 5 point scale ranging from 0 to 4, based on the investigator's assessment of the average elevation, erythema, and scaling of all psoriatic lesions at the current visit. A lower score indicates less severe psoriasis (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe). Analysis population: Full analysis set participants with a Baseline sIGA score ≥2; participants who prematurely discontinued from study drug prior to Week 16 or for whom sIGA data were missing at Week 16 were considered non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	313	330	322	324
Units: percentage of participants
number (confidence interval 95%)	10.9 (7.4 to 14.3)	38.5 (33.2 to 43.7)	41.9 (36.5 to 47.3)	54.0 (48.6 to 59.4)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

635

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[5]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

31.1

Confidence interval

level

95%

sides

2-sided

lower limit

24.7

upper limit

37.5

Notes
[5] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

637

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[6]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

43.1

Confidence interval

level

95%

sides

2-sided

lower limit

36.7

upper limit

49.6

Notes
[6] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16

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End point title

Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16

End point description

PASI is a composite score based on percentage of body surface area (BSA) affected by psoriasis and intensity of erythema (reddening), induration (thickening or hardening of the skin), and desquamation (peeling of the skin) of lesions assessed at 4 anatomic sites (head, upper extremities, trunk, and lower extremities). At each location, percentage of BSA involvement is assigned a score from 0 (no involvement) to 6 (90% to 100% involvement), and erythema, induration, and desquamation are scored on a scale from 0 (no symptoms) to 4 (very marked). PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). PASI-75 response is percentage of subjects who achieved at least a 75% reduction (improvement) from Baseline in PASI score. Analysis population: FAS subjects w/ Baseline psoriasis BSA involvement ≥3%; those who prematurely discontinued from study drug prior to Week 16 or for whom PASI data were missing at Week 16 were considered non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	211	211	214	210
Units: percentage of participants
number (confidence interval 95%)	21.3 (15.8 to 26.9)	53.1 (46.3 to 59.8)	62.6 (56.1 to 69.1)	62.4 (55.8 to 68.9)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

425

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

41.3

Confidence interval

level

95%

sides

2-sided

lower limit

32.8

upper limit

49.8

Notes
[7] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

421

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

41.1

Confidence interval

level

95%

sides

2-sided

lower limit

32.5

upper limit

49.6

Notes
[8] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Change From Baseline in Modified PsA Total Sharp/Van Der Heijde Score (mTSS) at Week 24

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End point title

Change From Baseline in Modified PsA Total Sharp/Van Der Heijde Score (mTSS) at Week 24

End point description

The Sharp–van der Heijde modified scoring method for PsA measures level of joint damage from radiographs of hands/feet, assessed by 2 readers. Joint erosion severity assessed in 20 joints in each hand/wrist and 6 joints in each foot. Each joint scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). Total erosion score ranges from 0 to 320 (worst). Joint space narrowing (JSN) assessed in 20 joints of each hand/wrist, and 6 joints of each foot, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). Total JSN score ranges from 0 to 208 (worst). Joints with gross osteolysis/pencil in cup were assigned maximum score for both erosions and JSN. Total mTSS score is sum of joint erosion and JSN scores, ranging from 0 (normal) to 528 (worst). A negative change from Baseline = improvement in joint damage. Analysis population: FAS w/available data at Baseline; linear extrapolation used for discontinued/rescued before Wk 24

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	372	384	391	383
Units: score on a scale
least squares mean (confidence interval 95%)	0.25 (0.13 to 0.36)	0.01 (-0.11 to 0.13)	-0.04 (-0.16 to 0.07)	0.03 (-0.08 to 0.15)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

763

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002 ^[9]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

-0.14

Notes
[9] - ANCOVA model including treatment and the stratification factor current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

755

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0069 ^[10]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

-0.06

Notes
[10] - ANCOVA model including treatment and the stratification factor current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24

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End point title

Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24

End point description

A participant was classified as achieving MDA if 5 of the following 7 criteria were met: •Tender joint count (out of 68 joints) ≤1 •Swollen joint count (out of 66 joints) ≤1 •PASI score ≤1 (score ranges from 0 - 72) or percent BSA involved with psoriasis ≤3% •Patient's assessment of pain ≤1.5 (NRS from 0 to 10) •Patient's Global Assessment of disease activity ≤2 (NRS from 0 to 10) •HAQ-DI score ≤0.5 (index score ranges from 0 to 3) •Leeds Enthesitis Index ≤1 (assesses the presence or absence of enthesitis at 3 bilateral sites, with an overall score range from 0 to 6) Analysis population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 24 or for whom data were missing at Week 24, or who met the rescue criteria at Week 16 were considered non-responders.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	423	429	429	423
Units: percentage of participants
number (confidence interval 95%)	12.3 (9.2 to 15.4)	33.3 (28.9 to 37.8)	36.6 (32.0 to 41.2)	45.4 (40.6 to 50.1)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

18.8

upper limit

29.8

Notes
[11] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

846

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

33.1

Confidence interval

level

95%

sides

2-sided

lower limit

27.4

upper limit

38.8

Notes
[12] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants With Resolution of Enthesitis at Week 24

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End point title

Percentage of Participants With Resolution of Enthesitis at Week 24

End point description

Resolution of enthesitis is defined as a Leeds Enthesitis Index (LEI) score = 0. LEI is an enthesitis measure developed specifically for PsA and assesses the presence or absence of tenderness at the following 3 bilateral enthesial sites: medial femoral condyles, lateral epicondyles of the humerus, and Achilles tendon insertions. Tenderness on examination is recorded as either present (coded as 1), absent (coded as 0), or not assessed for each of the 6 sites. The LEI is calculated by taking the sum of the scores from the 6 sites. The LEI ranges from 0 to 6 (worst). Analysis population: Full analysis set participants with a Baseline LEI > 0; participants who prematurely discontinued from study drug prior to Week 24 or for whom data were missing at Week 24, or who met the rescue criteria at Week 16 were considered non-responders.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	241	265	270	267
Units: percentage of participants
number (confidence interval 95%)	32.4 (26.5 to 38.3)	47.2 (41.2 to 53.2)	53.7 (47.8 to 59.7)	57.7 (51.8 to 63.6)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[13]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

21.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

29.7

Notes
[13] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

508

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

25.3

Confidence interval

level

95%

sides

2-sided

lower limit

16.9

upper limit

33.7

Notes
[14] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants With an ACR20 Response at Week 12 - Non-inferiority Versus Adalimumab

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End point title

Percentage of Participants With an ACR20 Response at Week 12 - Non-inferiority Versus Adalimumab

End point description

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	423	429	429	423
Units: percentage of participants
number (confidence interval 95%)	36.2 (31.6 to 40.7)	65.0 (60.5 to 69.5)	70.6 (66.3 to 74.9)	78.5 (74.6 to 82.4)

Upadacitinib 15 mg vs Adalimumab 40 mg

Statistical analysis description

Non-inferiority of each upadacitinib dose versus adalimumab was assessed using Koch’s 3-arm approach; non-inferiority was achieved if upadacitinib preserved at least 50% of the placebo-subtracted adalimumab effect. The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified αtransfer path.

Comparison groups

Adalimumab 40 mg v Upadacitinib 15 mg

Number of subjects included in analysis

858

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[15]

Method

Koch 3-Arm Test

Parameter type

Percent Adalimumab Effect Preservation

Point estimate

119.381

Confidence interval

level

95%

sides

2-sided

lower limit

97.987

upper limit

147.942

Notes
[15] - The percent of adalimumab effect preservation is the point estimate of 3-arm non-inferiority analysis, which is calculated by (Upadacitinib - Placebo) / (Adalimumab - Placebo) * 100.

Upadacitinib 30 mg vs Adalimumab 40 mg

Statistical analysis description

Comparison groups

Adalimumab 40 mg v Upadacitinib 30 mg

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[16]

Method

Koch 3-Arm Test

Parameter type

Percent Adalimumab Effect Preservation

Point estimate

146.604

Confidence interval

level

95%

sides

2-sided

lower limit

122.817

upper limit

180.398

Notes
[16] - The percent of adalimumab effect preservation is the point estimate of 3-arm non-inferiority analysis, which is calculated by (Upadacitinib - Placebo) / (Adalimumab - Placebo) * 100.

Secondary: Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12

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End point title

Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12

End point description

The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/ quality of life; a positive change from Baseline score indicates an improvement. Analysis population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	394	410	405	398
Units: score on a scale
least squares mean (confidence interval 95%)	3.19 (2.41 to 3.96)	6.82 (6.07 to 7.58)	7.86 (7.09 to 8.63)	8.90 (8.13 to 9.68)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

799

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

4.67

Confidence interval

level

95%

sides

2-sided

lower limit

3.67

upper limit

5.67

Notes
[17] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate.

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[18]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

5.72

Confidence interval

level

95%

sides

2-sided

lower limit

4.71

upper limit

6.72

Notes
[18] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate.

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12

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End point title

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12

End point description

The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days, including physical fatigue (e.g., I feel tired), functional fatigue (e.g., trouble finishing things), emotional fatigue (e.g., frustration), and social consequences of fatigue (e.g., limits social activity). Participants respond to the questions on a scale from 0 'not at all' to 4 'very much'. The FACIT Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement. Analysis population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	394	410	404	398
Units: score on a scale
least squares mean (confidence interval 95%)	2.8 (1.9 to 3.7)	5.7 (4.8 to 6.6)	6.3 (5.4 to 7.2)	7.1 (6.2 to 8.0)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[19]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

4.7

Notes
[19] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate.

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[20]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

4.3

Confidence interval

level

95%

sides

2-sided

lower limit

3.1

upper limit

5.5

Notes
[20] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate.

Secondary: Percentage of Participants With an ACR20 Response at Week 12 - Superiority Versus Adalimumab

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End point title

Percentage of Participants With an ACR20 Response at Week 12 - Superiority Versus Adalimumab

End point description

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	423	429	429	423
Units: percentage of participants
number (confidence interval 95%)	36.2 (31.6 to 40.7)	65.0 (60.5 to 69.5)	70.6 (66.3 to 74.9)	78.5 (74.6 to 82.4)

Upadacitinib 15 mg vs Adalimumab 40 mg

Statistical analysis description

Comparison groups

Upadacitinib 15 mg v Adalimumab 40 mg

Number of subjects included in analysis

858

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0815 ^[21]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

11.8

Notes
[21] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no).

Upadacitinib 30 mg vs Adalimumab 40 mg

Statistical analysis description

Comparison groups

Upadacitinib 30 mg v Adalimumab 40 mg

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[22]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

7.5

upper limit

19.4

Notes
[22] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no).

Secondary: Percentage of Participants With Resolution of Dactylitis at Week 24

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End point title

Percentage of Participants With Resolution of Dactylitis at Week 24

End point description

Resolution of dactylitis is defined as Leeds Dactylitis Index (LDI) score = 0. LDI is a score based on finger circumference and tenderness, assessed and summed across all fingers and toes. The presence of a dactylitic digit is defined as at least one affected AND tender digit with circumference increase over reference digit ≥10%. Reference digit circumference is either the contralateral digit (unaffected digit on opposite hand or foot) if available, or from a standard reference table if otherwise. Tenderness of affected digits is assessed on a scale from 0 [none] to 3 [worst]. Ratio of circumference between an affected digit and reference digit is multiplied by tenderness score for each affected digit. Results from each involved digit are summed to provide final LDI. A higher LDI indicates worse dactylitis. Analysis population: FAS w/ BL LDI > 0; those who stopped study drug prior to Wk 24, had missing data at Wk 24, or met rescue criteria at Wk 16 were considered nonresponders.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	126	127	136	127
Units: percentage of participants
number (confidence interval 95%)	39.7 (31.1 to 48.2)	74.0 (66.4 to 81.6)	76.5 (69.3 to 83.6)	79.5 (72.5 to 86.5)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

262

Analysis specification

Pre-specified

Analysis type

other ^[23]

P-value

< 0.0001 ^[24]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

36.8

Confidence interval

level

95%

sides

2-sided

lower limit

25.7

upper limit

47.9

Notes
[23] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[24] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

253

Analysis specification

Pre-specified

Analysis type

other ^[25]

P-value

< 0.0001 ^[26]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

39.8

Confidence interval

level

95%

sides

2-sided

lower limit

28.8

upper limit

50.9

Notes
[25] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[26] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Change From Baseline in Patient's Assessment of Pain - Superiority Versus Adalimumab

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End point title

Change From Baseline in Patient's Assessment of Pain - Superiority Versus Adalimumab

End point description

Participants were asked to indicate the severity of their arthritis pain within the previous week on a numerical rating scale (NRS) from 0 to 10. A score of 0 indicates "no pain" and a score of 10 indicates "worst possible pain." A negative change from Baseline indicates improvement. Analysis population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	392	406	404	398
Units: units on a scale
least squares mean (confidence interval 95%)	-0.9 (-1.2 to -0.7)	-2.3 (-2.5 to -2.1)	-2.3 (-2.5 to -2.0)	-2.7 (-2.9 to -2.5)

Upadacitinib 15 mg vs Adalimumab 40 mg

Statistical analysis description

Comparison groups

Adalimumab 40 mg v Upadacitinib 15 mg

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

other ^[27]

P-value

= 0.897 ^[28]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.3

Notes
[27] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[28] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Adalimumab

Upadacitinib 30 mg vs Adalimumab 40 mg

Statistical analysis description

Comparison groups

Adalimumab 40 mg v Upadacitinib 30 mg

Number of subjects included in analysis

804

Analysis specification

Pre-specified

Analysis type

other ^[29]

P-value

= 0.0028 ^[30]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.2

Notes
[29] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[30] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Adalimumab

Secondary: Change From Baseline in HAQ-DI - Superiority Versus Adalimumab

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End point title

Change From Baseline in HAQ-DI - Superiority Versus Adalimumab

End point description

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement. Analysis population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	392	406	404	398
Units: score on a scale
least squares mean (confidence interval 95%)	-0.14 (-0.18 to -0.09)	-0.34 (-0.38 to -0.29)	-0.42 (-0.47 to -0.37)	-0.47 (-0.52 to -0.42)

Upadacitinib 15 mg vs Adalimumab 40 mg

Statistical analysis description

Comparison groups

Adalimumab 40 mg v Upadacitinib 15 mg

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

other ^[31]

P-value

= 0.0162 ^[32]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

-0.01

Notes
[31] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[32] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Adalimumab

Upadacitinib 30 mg vs Adalimumab 40 mg

Statistical analysis description

Comparison groups

Upadacitinib 30 mg v Adalimumab 40 mg

Number of subjects included in analysis

804

Analysis specification

Pre-specified

Analysis type

other ^[33]

P-value

< 0.0001 ^[34]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

-0.07

Notes
[33] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[34] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Adalimumab

Secondary: Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire at Week 16

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End point title

Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire at Week 16

End point description

The SAPS is an 11-item self-assessment of psoriasis symptoms that includes questions on: pain, itching, redness, scaling, flaking, bleeding, burning, stinging, tenderness, pain due to skin cracking, and joint pain. Each item is scored from 0 to 10, with 0 being least severe and 10 being most severe. The total score is generated by summing the 11 items and ranges from 0 to 110 (worst). A negative change from Baseline in the total score indicates improvement. Analysis population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 16 was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	388	407	396	395
Units: score on a scale
least squares mean (confidence interval 95%)	-8.2 (-10.2 to -6.3)	-22.7 (-24.7 to -20.8)	-25.3 (-27.3 to -23.4)	-28.1 (-30.0 to -26.1)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

Comparison groups

Upadacitinib 15 mg v Placebo

Number of subjects included in analysis

784

Analysis specification

Pre-specified

Analysis type

other ^[35]

P-value

< 0.0001 ^[36]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

-17.1

Confidence interval

level

95%

sides

2-sided

lower limit

-19.6

upper limit

-14.6

Notes
[35] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[36] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

783

Analysis specification

Pre-specified

Analysis type

other ^[37]

P-value

< 0.0001 ^[38]

Method

Mixed Effect Model Repeated Measurement

Parameter type

LS Mean Difference

Point estimate

-19.8

Confidence interval

level

95%

sides

2-sided

lower limit

-22.3

upper limit

-17.3

Notes
[37] - This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg.
[38] - MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. Treatment Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12

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End point title

Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12

End point description

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: 1. ≥50% improvement in 68-tender joint count; 2. ≥50% improvement in 66-swollen joint count; and 3. ≥50% improvement in at least 3 of the 5 following parameters: •Physician global assessment of disease activity •Patient global assessment of disease activity •Patient assessment of pain •Health Assessment Questionnaire - Disability Index (HAQ-DI) •High-sensitivity C-reactive protein (hsCRP). Analysis population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	423	429	429	423
Units: percentage of participants
number (confidence interval 95%)	13.2 (10.0 to 16.5)	37.5 (32.9 to 42.1)	37.5 (32.9 to 42.1)	51.8 (47.0 to 56.5)

Upadacitinib 15 mg vs Placebo

Statistical analysis description

This comparison was not part of the pre-specified multiplicity testing sequence.

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[39]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

18.7

upper limit

29.9

Notes
[39] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Statistical analysis description

This comparison was not part of the pre-specified multiplicity testing sequence.

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

846

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[40]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

38.5

Confidence interval

level

95%

sides

2-sided

lower limit

32.8

upper limit

44.3

Notes
[40] - Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12

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End point title

Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12

End point description

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: 1. ≥70% improvement in 68-tender joint count; 2. ≥70% improvement in 66-swollen joint count; and 3. ≥70% improvement in at least 3 of the 5 following parameters: •Physician global assessment of disease activity •Patient global assessment of disease activity •Patient assessment of pain •Health Assessment Questionnaire - Disability Index (HAQ-DI) •High-sensitivity C-reactive protein (hsCRP). Analysis population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	423	429	429	423
Units: percentage of participants
number (confidence interval 95%)	2.4 (0.9 to 3.8)	13.8 (10.5 to 17.0)	15.6 (12.2 to 19.1)	25.3 (21.2 to 29.4)

Upadacitinib 15 mg vs Placebo

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

other ^[41]

P-value

< 0.0001 ^[42]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

13.3

Confidence interval

level

95%

sides

2-sided

lower limit

9.5

upper limit

Notes
[41] - This comparison was not part of the pre-specified multiplicity testing sequence.
[42] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

846

Analysis specification

Pre-specified

Analysis type

other ^[43]

P-value

< 0.0001 ^[44]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

22.9

Confidence interval

level

95%

sides

2-sided

lower limit

18.5

upper limit

27.3

Notes
[43] - This comparison was not part of the pre-specified multiplicity testing sequence.
[44] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Secondary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2

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End point title

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2

End point description

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. ≥20% improvement in 68-tender joint count; 2. ≥20% improvement in 66-swollen joint count; and 3. ≥20% improvement in at least 3 of the 5 following parameters: •Physician global assessment of disease activity •Patient global assessment of disease activity •Patient assessment of pain •Health Assessment Questionnaire - Disability Index (HAQ-DI) •High-sensitivity C-reactive protein (hsCRP). Analysis population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 2 or for whom ACR data were missing at Week 2 were considered non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 2

End point values	Placebo	Adalimumab 40 mg	Upadacitinib 15 mg	Upadacitinib 30 mg
Number of subjects analysed	423	429	429	423
Units: percentage of participants
number (confidence interval 95%)	12.1 (9.0 to 15.2)	30.3 (26.0 to 34.7)	28.2 (23.9 to 32.5)	38.3 (33.7 to 42.9)

Upadacitinib 15 mg vs Placebo

Comparison groups

Placebo v Upadacitinib 15 mg

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

other ^[45]

P-value

< 0.0001 ^[46]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

16.1

Confidence interval

level

95%

sides

2-sided

lower limit

10.9

upper limit

21.4

Notes
[45] - This comparison was not part of the pre-specified multiplicity testing sequence.
[46] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Upadacitinib 30 mg vs Placebo

Comparison groups

Placebo v Upadacitinib 30 mg

Number of subjects included in analysis

846

Analysis specification

Pre-specified

Analysis type

other ^[47]

P-value

< 0.0001 ^[48]

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

26.2

Confidence interval

level

95%

sides

2-sided

lower limit

20.7

upper limit

31.8

Notes
[47] - This comparison was not part of the pre-specified multiplicity testing sequence.
[48] - Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). Response Rate Difference = Upadacitinib - Placebo

Adverse events

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Timeframe for reporting adverse events

Median time on follow-up in Period 1 (days): Upa 15 mg (415); Upa 30 mg (414); Ada 40 mg (194); Pbo up to Wk 24 (418); Pbo/Upa 15 mg Wk 24-56 (419); and Pbo/Upa 30 mg Wk 24-56 (776.5).

Adverse event reporting additional description

Median time on follow-up in Period 2 (days): Upa 15 mg (1458); Upa 30 mg (796.5); Ada 40 mg (1486); Pbo/Upa 15 mg (1459); Pbo/Upa 30 mg (790.5); and Upa 30 mg/Upa 15 mg (842).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

Upadacitinib 30 mg Period 1 (Weeks 1 to 56)

Reporting group description

Participants randomized to receive upadacitinib 30 mg orally once a day (QD) and matching placebo to adalimumab by subcutaneous injection every other week (EOW) for 56 weeks in Period 1.

Reporting group title

Upadacitinib 15 mg Period 1 (Weeks 1 to 56)

Reporting group description

Participants randomized to receive upadacitinib 15 mg orally once a day (QD) and matching placebo to adalimumab by subcutaneous injection every other week (EOW) for 56 weeks in Period 1.

Reporting group title

Adalimumab 40 mg Period 1 (Weeks 1 to 56)

Reporting group description

Participants randomized to receive adalimumab 40 mg by subcutaneous injection every other week (EOW) and matching placebo to upadacitinib orally once a day (QD) for 56 weeks in Period 1.

Reporting group title

Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Adalimumab 40 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Placebo / Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Placebo / Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Reporting group description

Reporting group title

Upadacitinib 30 mg / Upadacitinib 15 mg Period 2 (Wks 56 -260)

Reporting group description

Participants randomized to receive upadacitinib 30 mg orally once a day (QD) who were switched to upadacitinib 15 mg orally once a day (QD) at their next scheduled study visit in Period 2 after Protocol Amendment 7 was approved (30 January 2021).

Reporting group title

Placebo / Upadacitinib 15 mg Period 1 (Weeks 24 to 56)

Reporting group description

Reporting group title

Placebo Period 1 (Weeks 1 to 24)

Reporting group description

Participants randomized to receive matching placebo to upadacitinib orally once a day (QD) for 24 weeks, as well as matching placebo to adalimumab administered by subcutaneous injection every other week (EOW) from Weeks 1 to 24 in Period 1.

Reporting group title

Placebo / Upadacitinib 30 mg Period 1 (Weeks 24 to 56)

Reporting group description

Upadacitinib 30 mg Period 1 (Weeks 1 to 56)

Upadacitinib 15 mg Period 1 (Weeks 1 to 56)

Adalimumab 40 mg Period 1 (Weeks 1 to 56)

Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Adalimumab 40 mg Period 2 (Weeks 56 to 260)

Placebo / Upadacitinib 15 mg Period 2 (Weeks 56 to 260)

Placebo / Upadacitinib 30 mg Period 2 (Weeks 56 to 260)

Upadacitinib 30 mg / Upadacitinib 15 mg Period 2 (Wks 56 -260)

Placebo / Upadacitinib 15 mg Period 1 (Weeks 24 to 56)

Placebo Period 1 (Weeks 1 to 24)

Placebo / Upadacitinib 30 mg Period 1 (Weeks 24 to 56)

Total subjects affected by serious adverse events

subjects affected / exposed

46 / 423 (10.87%)

28 / 430 (6.51%)

35 / 429 (8.16%)

108 / 378 (28.57%)

65 / 366 (17.76%)

72 / 366 (19.67%)

34 / 177 (19.21%)

25 / 178 (14.04%)

55 / 443 (12.42%)

10 / 188 (5.32%)

13 / 423 (3.07%)

11 / 190 (5.79%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

ADENOCARCINOMA GASTRIC

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

ADENOCARCINOMA OF COLON

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BLADDER TRANSITIONAL CELL CARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BASAL CELL CARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BREAST CANCER STAGE II

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CLEAR CELL RENAL CELL CARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HORMONE RECEPTOR POSITIVE HER2 NEGATIVE BREAST CANCER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HAEMANGIOMA OF LIVER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENDOMETRIAL ADENOCARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COLON CANCER METASTATIC

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LUNG ADENOCARCINOMA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LARYNGEAL NEOPLASM

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INVASIVE DUCTAL BREAST CARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

2 / 366 (0.55%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INVASIVE BREAST CARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

2 / 366 (0.55%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

LUNG ADENOCARCINOMA STAGE IV

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LUNG CANCER METASTATIC

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

MALIGNANT MELANOMA IN SITU

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MYELOFIBROSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

METASTATIC SQUAMOUS CELL CARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OVARIAN CANCER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NEUROMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NEUROENDOCRINE CARCINOMA OF THE SKIN

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PANCREATIC CARCINOMA METASTATIC

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PANCREATIC NEOPLASM

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PAPILLARY THYROID CANCER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PLASMA CELL MYELOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

POORLY DIFFERENTIATED THYROID CARCINOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PROSTATE CANCER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RENAL CANCER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SCHWANNOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SQUAMOUS CELL CARCINOMA OF THE CERVIX

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SQUAMOUS CELL CARCINOMA OF SKIN

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

THYROID ADENOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UTERINE LEIOMYOMA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

UTERINE CANCER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

AORTIC STENOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CIRCULATORY COLLAPSE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

DEEP VEIN THROMBOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SUPERFICIAL VEIN THROMBOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SHOCK HAEMORRHAGIC

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HYPOTENSION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VARICOSE VEIN

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

ABORTION SPONTANEOUS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UNINTENDED PREGNANCY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

CHEST PAIN

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CYST RUPTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DROWNING

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

DEATH

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

MULTIPLE ORGAN DYSFUNCTION SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

PAIN

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PYREXIA

subjects affected / exposed

2 / 423 (0.47%)

1 / 430 (0.23%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

2 / 2

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RETENTION CYST

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SUDDEN DEATH

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

2 / 177 (1.13%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

Immune system disorders

HYPERSENSITIVITY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

IMMUNE SYSTEM DISORDER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

BENIGN PROSTATIC HYPERPLASIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FALLOPIAN TUBE CYST

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENDOMETRIAL HYPERTROPHY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENDOMETRIAL HYPERPLASIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CERVICAL POLYP

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FIBROCYSTIC BREAST DISEASE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HAEMORRHAGIC OVARIAN CYST

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HEAVY MENSTRUAL BLEEDING

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OVARIAN CYST

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OVARIAN STROMAL HYPERPLASIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UTERINE HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UTERINE POLYP

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VAGINAL PROLAPSE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UTERINE PROLAPSE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

ACUTE RESPIRATORY DISTRESS SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ASPHYXIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ACUTE RESPIRATORY FAILURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

3 / 378 (0.79%)

2 / 366 (0.55%)

0 / 366 (0.00%)

1 / 177 (0.56%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DYSPNOEA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COUGH

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

EPISTAXIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HYPERVENTILATION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INTERSTITIAL LUNG DISEASE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

2 / 366 (0.55%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

OBSTRUCTIVE AIRWAYS DISORDER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OBSTRUCTIVE SLEEP APNOEA SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PLEURAL EFFUSION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMOTHORAX

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMOTHORAX SPONTANEOUS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PULMONARY FIBROSIS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PULMONARY EMBOLISM

subjects affected / exposed

1 / 423 (0.24%)

1 / 430 (0.23%)

0 / 429 (0.00%)

3 / 378 (0.79%)

4 / 366 (1.09%)

1 / 366 (0.27%)

0 / 177 (0.00%)

2 / 178 (1.12%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

2 / 3

1 / 4

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

RESPIRATORY DISTRESS

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TONSILLAR HYPERTROPHY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TONSILLAR HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

BIPOLAR DISORDER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BIPOLAR I DISORDER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ANXIETY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MAJOR DEPRESSION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DEPRESSION

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

BLOOD CREATINE PHOSPHOKINASE INCREASED

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BLOOD CREATININE INCREASED

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CORTISOL ABNORMAL

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

WEIGHT INCREASED

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

ANKLE FRACTURE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 366 (0.27%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CHEST INJURY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CLAVICLE FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COMMINUTED FRACTURE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CONCUSSION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FEMORAL NECK FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FEMUR FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FRACTURE DISPLACEMENT

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FOOT FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HAND FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HIP FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HUMERUS FRACTURE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INCISIONAL HERNIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

JOINT DISLOCATION

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

JOINT INJURY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MENISCUS INJURY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MUSCULOSKELETAL FOREIGN BODY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OPTIC NERVE INJURY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PATELLA FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMOTHORAX TRAUMATIC

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RADIUS FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 366 (0.27%)

1 / 177 (0.56%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RIB FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ROAD TRAFFIC ACCIDENT

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

SOFT TISSUE FOREIGN BODY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SPINAL FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

STRESS FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UPPER LIMB FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

TRAUMATIC LIVER INJURY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TIBIA FRACTURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TENDON RUPTURE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

WOUND DEHISCENCE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

HYDROCELE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

ACUTE MYOCARDIAL INFARCTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

1 / 366 (0.27%)

2 / 366 (0.55%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

ANGINA PECTORIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

AORTIC VALVE STENOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ARTERIOSCLEROSIS CORONARY ARTERY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

ATRIAL FLUTTER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

2 / 366 (0.55%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

ATRIAL FIBRILLATION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

4 / 378 (1.06%)

1 / 366 (0.27%)

3 / 366 (0.82%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 4

0 / 1

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

ATRIOVENTRICULAR BLOCK SECOND DEGREE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CARDIAC DISORDER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CARDIAC ARREST

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

CARDIAC FAILURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

2 / 443 (0.45%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

CARDIAC FAILURE ACUTE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CARDIAC FAILURE CONGESTIVE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CHRONIC CORONARY SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CARDIOGENIC SHOCK

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LEFT VENTRICULAR DYSFUNCTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CORONARY ARTERY DISEASE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

2 / 366 (0.55%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

1 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MYOCARDIAL INFARCTION

subjects affected / exposed

2 / 423 (0.47%)

1 / 430 (0.23%)

0 / 429 (0.00%)

3 / 378 (0.79%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 1

0 / 0

2 / 3

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

PAROXYSMAL ATRIOVENTRICULAR BLOCK

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MYOCARDIAL ISCHAEMIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PERICARDITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

2 / 366 (0.55%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

AMYOTROPHIC LATERAL SCLEROSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CARPAL TUNNEL SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CEREBRAL HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CEREBROVASCULAR ACCIDENT

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CEREBRAL INFARCTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DEMYELINATION

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CERVICAL RADICULOPATHY

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIABETIC NEUROPATHY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HEADACHE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ISCHAEMIC STROKE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HEPATIC ENCEPHALOPATHY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LACUNAR STROKE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LUMBAR RADICULOPATHY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

2 / 366 (0.55%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

NERVE COMPRESSION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RADICULOPATHY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SUBARACHNOID HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SCIATICA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SYNCOPE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TRANSIENT ISCHAEMIC ATTACK

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VITH NERVE PARALYSIS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VERTEBROBASILAR INSUFFICIENCY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

ANAEMIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LYMPHADENOPATHY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

IRON DEFICIENCY ANAEMIA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ANAEMIA MACROCYTIC

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NORMOCHROMIC NORMOCYTIC ANAEMIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LYMPHOID TISSUE HYPERPLASIA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

SUDDEN HEARING LOSS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VERTIGO POSITIONAL

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VERTIGO

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

EYELID PTOSIS

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIPLOPIA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CATARACT

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RETINAL DETACHMENT

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VISUAL ACUITY REDUCED

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

ABDOMINAL STRANGULATED HERNIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ABDOMINAL ADHESIONS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ANAL FISTULA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ASCITES

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COLITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CROHN'S DISEASE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DUODENAL ULCER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DUODENAL ULCER HAEMORRHAGE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DYSPEPSIA

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENTERITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FAECALOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

ENTEROVESICAL FISTULA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENTEROCOLITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FOOD POISONING

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTRIC ULCER PERFORATION

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTRITIS EROSIVE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTRODUODENAL HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTROINTESTINAL HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTROINTESTINAL PAIN

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTROINTESTINAL PERFORATION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

GASTROOESOPHAGEAL REFLUX DISEASE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HAEMATEMESIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

INGUINAL HERNIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

2 / 366 (0.55%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HIATUS HERNIA

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HAEMORRHOIDS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

LARGE INTESTINE POLYP

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INTESTINAL POLYP

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INTESTINAL OBSTRUCTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

2 / 366 (0.55%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

MESENTERIC VEIN THROMBOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UMBILICAL HERNIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OESOPHAGEAL SPASM

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RETROPERITONEAL HAEMATOMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RETROPERITONEAL HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UPPER GASTROINTESTINAL HAEMORRHAGE

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VOMITING

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

BILE DUCT STONE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BILIARY COLIC

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CHOLECYSTITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CHOLECYSTITIS ACUTE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HEPATIC FAILURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CHOLELITHIASIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

3 / 378 (0.79%)

0 / 366 (0.00%)

2 / 366 (0.55%)

0 / 177 (0.00%)

1 / 178 (0.56%)

2 / 443 (0.45%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 2

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HEPATITIS ACUTE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HEPATIC STEATOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

JAUNDICE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PORTAL VEIN THROMBOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

ANGIOEDEMA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DERMATITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DERMATOMYOSITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DERMATITIS EXFOLIATIVE GENERALISED

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DERMATITIS CONTACT

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INGROWING NAIL

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PSORIASIS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PUSTULAR PSORIASIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

CALCULUS URINARY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ACUTE KIDNEY INJURY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HAEMATURIA

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RENAL FAILURE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RENAL COLIC

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INCONTINENCE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NEPHROLITHIASIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

1 / 378 (0.26%)

2 / 366 (0.55%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

STRESS URINARY INCONTINENCE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

URETEROLITHIASIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

URETHRAL STENOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

GOITRE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

ARTHRALGIA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BACK PAIN

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FACET JOINT SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CERVICAL SPINAL STENOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BURSITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FOOT DEFORMITY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

3 / 366 (0.82%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FRACTURE NONUNION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INTERVERTEBRAL DISC DEGENERATION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INTERVERTEBRAL DISC DISORDER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INTERVERTEBRAL DISC PROTRUSION

subjects affected / exposed

2 / 423 (0.47%)

0 / 430 (0.00%)

1 / 429 (0.23%)

2 / 378 (0.53%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

JAW DISORDER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NECK PAIN

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

LUMBAR SPINAL STENOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OSTEOARTHRITIS

subjects affected / exposed

2 / 423 (0.47%)

0 / 430 (0.00%)

3 / 429 (0.70%)

5 / 378 (1.32%)

3 / 366 (0.82%)

5 / 366 (1.37%)

1 / 177 (0.56%)

1 / 178 (0.56%)

5 / 443 (1.13%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 3

0 / 5

0 / 3

0 / 5

0 / 1

0 / 5

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

ROTATOR CUFF SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

3 / 378 (0.79%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

PSORIATIC ARTHROPATHY

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OSTEONECROSIS

subjects affected / exposed

2 / 423 (0.47%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SNAPPING HIP SYNDROME

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SPINAL OSTEOARTHRITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SPINAL RETROLISTHESIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SPINAL STENOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SPONDYLOLISTHESIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

ABSCESS LIMB

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ANAL ABSCESS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

APPENDICITIS

subjects affected / exposed

1 / 423 (0.24%)

1 / 430 (0.23%)

0 / 429 (0.00%)

3 / 378 (0.79%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

1 / 1

0 / 1

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

1 / 1

0 / 1

deaths causally related to treatment / all

0 / 0

ATYPICAL PNEUMONIA

subjects affected / exposed

2 / 423 (0.47%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

ARTHRITIS BACTERIAL

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BACTERAEMIA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BREAST ABSCESS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

1 / 423 (0.24%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BONE ABSCESS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BRONCHITIS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

CHRONIC TONSILLITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

2 / 366 (0.55%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

CELLULITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

1 / 378 (0.26%)

1 / 366 (0.27%)

2 / 366 (0.55%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

1 / 1

2 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COVID-19 PNEUMONIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

20 / 378 (5.29%)

19 / 366 (5.19%)

4 / 366 (1.09%)

9 / 177 (5.08%)

8 / 178 (4.49%)

7 / 443 (1.58%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 20

3 / 19

2 / 4

2 / 9

3 / 8

0 / 7

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 3

0 / 1

1 / 2

0 / 2

0 / 0

COVID-19

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

12 / 378 (3.17%)

9 / 366 (2.46%)

4 / 366 (1.09%)

1 / 177 (0.56%)

1 / 178 (0.56%)

4 / 443 (0.90%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 12

0 / 9

0 / 4

0 / 1

1 / 1

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 4

0 / 1

0 / 0

0 / 1

0 / 0

CYSTITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIVERTICULITIS

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ENTEROCOCCAL BACTERAEMIA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIVERTICULITIS INTESTINAL PERFORATED

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ESCHERICHIA URINARY TRACT INFECTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ERYSIPELAS

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

3 / 443 (0.68%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

GASTROENTERITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

1 / 366 (0.27%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INFECTED DERMAL CYST

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HERPES ZOSTER

subjects affected / exposed

1 / 423 (0.24%)

1 / 430 (0.23%)

0 / 429 (0.00%)

1 / 378 (0.26%)

4 / 366 (1.09%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

4 / 4

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

HEPATITIS A

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

H1N1 INFLUENZA

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INFLUENZA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

1 / 188 (0.53%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LOWER RESPIRATORY TRACT INFECTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

LARYNGITIS

subjects affected / exposed

0 / 423 (0.00%)

1 / 430 (0.23%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

JOINT ABSCESS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NEUTROPENIC SEPSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMOCYSTIS JIROVECII PNEUMONIA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PERITONITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OPHTHALMIC HERPES ZOSTER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA

subjects affected / exposed

4 / 423 (0.95%)

2 / 430 (0.47%)

1 / 429 (0.23%)

7 / 378 (1.85%)

2 / 366 (0.55%)

1 / 366 (0.27%)

1 / 177 (0.56%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

2 / 423 (0.47%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

3 / 4

1 / 2

1 / 1

3 / 7

0 / 2

1 / 1

0 / 1

1 / 1

0 / 0

0 / 2

0 / 1

deaths causally related to treatment / all

0 / 0

PNEUMONIA ACINETOBACTER

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA ASPIRATION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA BACTERIAL

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA KLEBSIELLA

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA STREPTOCOCCAL

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PULMONARY TUBERCULOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PYELONEPHRITIS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

PYELONEPHRITIS ACUTE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SALPINGITIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

2 / 366 (0.55%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RENAL ABSCESS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SEPSIS

subjects affected / exposed

0 / 423 (0.00%)

2 / 430 (0.47%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

1 / 366 (0.27%)

1 / 177 (0.56%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

SEPTIC SHOCK

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

1 / 366 (0.27%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

SPUTUM PURULENT

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SKIN INFECTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

STAPHYLOCOCCAL BACTERAEMIA

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

STAPHYLOCOCCAL INFECTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

1 / 429 (0.23%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

STAPHYLOCOCCAL SEPSIS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SUBCUTANEOUS ABSCESS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

TOOTH INFECTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TUBERCULOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TUBERCULOUS PLEURISY

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 366 (0.27%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

URINARY TRACT INFECTION

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

2 / 443 (0.45%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

UROSEPSIS

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VIRAL INFECTION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

1 / 378 (0.26%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

1 / 190 (0.53%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

DECREASED APPETITE

subjects affected / exposed

1 / 423 (0.24%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIABETES MELLITUS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

2 / 378 (0.53%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

DEHYDRATION

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

0 / 178 (0.00%)

1 / 443 (0.23%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FRUCTOSE INTOLERANCE

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

0 / 177 (0.00%)

1 / 178 (0.56%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIABETIC KETOACIDOSIS

subjects affected / exposed

0 / 423 (0.00%)

0 / 430 (0.00%)

0 / 429 (0.00%)

0 / 378 (0.00%)

0 / 366 (0.00%)

1 / 177 (0.56%)

0 / 178 (0.00%)

0 / 443 (0.00%)

0 / 188 (0.00%)

0 / 423 (0.00%)

0 / 190 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Upadacitinib 30 mg Period 1 (Weeks 1 to 56)	Upadacitinib 15 mg Period 1 (Weeks 1 to 56)	Adalimumab 40 mg Period 1 (Weeks 1 to 56)	Upadacitinib 15 mg Period 2 (Weeks 56 to 260)	Upadacitinib 30 mg Period 2 (Weeks 56 to 260)	Adalimumab 40 mg Period 2 (Weeks 56 to 260)	Placebo / Upadacitinib 15 mg Period 2 (Weeks 56 to 260)	Placebo / Upadacitinib 30 mg Period 2 (Weeks 56 to 260)	Upadacitinib 30 mg / Upadacitinib 15 mg Period 2 (Wks 56 -260)	Placebo / Upadacitinib 15 mg Period 1 (Weeks 24 to 56)	Placebo Period 1 (Weeks 1 to 24)	Placebo / Upadacitinib 30 mg Period 1 (Weeks 24 to 56)
Total subjects affected by non serious adverse events
subjects affected / exposed	262 / 423 (61.94%)	248 / 430 (57.67%)	220 / 429 (51.28%)	274 / 378 (72.49%)	218 / 366 (59.56%)	245 / 366 (66.94%)	130 / 177 (73.45%)	112 / 178 (62.92%)	272 / 443 (61.40%)	62 / 188 (32.98%)	151 / 423 (35.70%)	76 / 190 (40.00%)
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
subjects affected / exposed	67 / 423 (15.84%)	52 / 430 (12.09%)	31 / 429 (7.23%)	43 / 378 (11.38%)	33 / 366 (9.02%)	21 / 366 (5.74%)	22 / 177 (12.43%)	25 / 178 (14.04%)	39 / 443 (8.80%)	11 / 188 (5.85%)	6 / 423 (1.42%)	15 / 190 (7.89%)
occurrences all number	95	69	38	76	43	34	33	32	46	13	7	17
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	29 / 423 (6.86%)	25 / 430 (5.81%)	28 / 429 (6.53%)	27 / 378 (7.14%)	23 / 366 (6.28%)	22 / 366 (6.01%)	14 / 177 (7.91%)	9 / 178 (5.06%)	18 / 443 (4.06%)	4 / 188 (2.13%)	8 / 423 (1.89%)	9 / 190 (4.74%)
occurrences all number	38	29	32	38	26	28	20	12	20	4	9	9
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	39 / 423 (9.22%)	32 / 430 (7.44%)	44 / 429 (10.26%)	33 / 378 (8.73%)	23 / 366 (6.28%)	30 / 366 (8.20%)	18 / 177 (10.17%)	9 / 178 (5.06%)	19 / 443 (4.29%)	6 / 188 (3.19%)	12 / 423 (2.84%)	8 / 190 (4.21%)
occurrences all number	52	45	53	48	28	35	25	15	21	6	14	8
Vascular disorders
HYPERTENSION
subjects affected / exposed	21 / 423 (4.96%)	33 / 430 (7.67%)	15 / 429 (3.50%)	39 / 378 (10.32%)	11 / 366 (3.01%)	26 / 366 (7.10%)	15 / 177 (8.47%)	10 / 178 (5.62%)	20 / 443 (4.51%)	2 / 188 (1.06%)	10 / 423 (2.36%)	2 / 190 (1.05%)
occurrences all number	22	37	15	44	12	27	18	10	21	2	10	2
Nervous system disorders
HEADACHE
subjects affected / exposed	21 / 423 (4.96%)	23 / 430 (5.35%)	23 / 429 (5.36%)	15 / 378 (3.97%)	13 / 366 (3.55%)	17 / 366 (4.64%)	6 / 177 (3.39%)	3 / 178 (1.69%)	12 / 443 (2.71%)	3 / 188 (1.60%)	10 / 423 (2.36%)	2 / 190 (1.05%)
occurrences all number	28	32	24	42	16	20	24	3	12	6	10	2
Blood and lymphatic system disorders
LEUKOPENIA
subjects affected / exposed	15 / 423 (3.55%)	16 / 430 (3.72%)	8 / 429 (1.86%)	21 / 378 (5.56%)	10 / 366 (2.73%)	9 / 366 (2.46%)	10 / 177 (5.65%)	4 / 178 (2.25%)	20 / 443 (4.51%)	1 / 188 (0.53%)	4 / 423 (0.95%)	3 / 190 (1.58%)
occurrences all number	20	19	10	30	14	15	16	5	23	1	4	8
LYMPHOPENIA
subjects affected / exposed	15 / 423 (3.55%)	10 / 430 (2.33%)	1 / 429 (0.23%)	13 / 378 (3.44%)	6 / 366 (1.64%)	1 / 366 (0.27%)	10 / 177 (5.65%)	6 / 178 (3.37%)	17 / 443 (3.84%)	1 / 188 (0.53%)	5 / 423 (1.18%)	1 / 190 (0.53%)
occurrences all number	17	15	1	26	9	2	12	6	24	1	5	1
NEUTROPENIA
subjects affected / exposed	21 / 423 (4.96%)	11 / 430 (2.56%)	16 / 429 (3.73%)	14 / 378 (3.70%)	14 / 366 (3.83%)	17 / 366 (4.64%)	8 / 177 (4.52%)	7 / 178 (3.93%)	12 / 443 (2.71%)	3 / 188 (1.60%)	1 / 423 (0.24%)	3 / 190 (1.58%)
occurrences all number	28	11	20	26	16	26	11	10	18	3	1	3
General disorders and administration site conditions
PYREXIA
subjects affected / exposed	16 / 423 (3.78%)	2 / 430 (0.47%)	5 / 429 (1.17%)	8 / 378 (2.12%)	5 / 366 (1.37%)	3 / 366 (0.82%)	9 / 177 (5.08%)	6 / 178 (3.37%)	8 / 443 (1.81%)	1 / 188 (0.53%)	4 / 423 (0.95%)	1 / 190 (0.53%)
occurrences all number	19	4	5	9	5	3	10	7	10	1	4	1
Gastrointestinal disorders
DIARRHOEA
subjects affected / exposed	23 / 423 (5.44%)	23 / 430 (5.35%)	19 / 429 (4.43%)	14 / 378 (3.70%)	9 / 366 (2.46%)	10 / 366 (2.73%)	7 / 177 (3.95%)	8 / 178 (4.49%)	7 / 443 (1.58%)	5 / 188 (2.66%)	10 / 423 (2.36%)	4 / 190 (2.11%)
occurrences all number	26	25	20	14	9	10	7	8	9	5	10	4
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	23 / 423 (5.44%)	12 / 430 (2.79%)	9 / 429 (2.10%)	16 / 378 (4.23%)	7 / 366 (1.91%)	9 / 366 (2.46%)	9 / 177 (5.08%)	4 / 178 (2.25%)	13 / 443 (2.93%)	3 / 188 (1.60%)	5 / 423 (1.18%)	3 / 190 (1.58%)
occurrences all number	28	13	9	17	9	12	10	4	13	3	5	3
Skin and subcutaneous tissue disorders
PSORIASIS
subjects affected / exposed	8 / 423 (1.89%)	9 / 430 (2.09%)	18 / 429 (4.20%)	22 / 378 (5.82%)	20 / 366 (5.46%)	23 / 366 (6.28%)	12 / 177 (6.78%)	4 / 178 (2.25%)	26 / 443 (5.87%)	0 / 188 (0.00%)	8 / 423 (1.89%)	0 / 190 (0.00%)
occurrences all number	11	10	20	24	28	29	14	4	31	0	8	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	5 / 423 (1.18%)	7 / 430 (1.63%)	4 / 429 (0.93%)	24 / 378 (6.35%)	8 / 366 (2.19%)	22 / 366 (6.01%)	13 / 177 (7.34%)	5 / 178 (2.81%)	15 / 443 (3.39%)	2 / 188 (1.06%)	2 / 423 (0.47%)	4 / 190 (2.11%)
occurrences all number	6	7	4	34	8	27	18	5	18	2	2	4
BACK PAIN
subjects affected / exposed	13 / 423 (3.07%)	8 / 430 (1.86%)	11 / 429 (2.56%)	29 / 378 (7.67%)	8 / 366 (2.19%)	18 / 366 (4.92%)	3 / 177 (1.69%)	8 / 178 (4.49%)	11 / 443 (2.48%)	0 / 188 (0.00%)	7 / 423 (1.65%)	3 / 190 (1.58%)
occurrences all number	13	8	13	29	8	20	3	8	11	0	8	6
OSTEOARTHRITIS
subjects affected / exposed	3 / 423 (0.71%)	6 / 430 (1.40%)	4 / 429 (0.93%)	12 / 378 (3.17%)	7 / 366 (1.91%)	14 / 366 (3.83%)	10 / 177 (5.65%)	3 / 178 (1.69%)	7 / 443 (1.58%)	2 / 188 (1.06%)	2 / 423 (0.47%)	0 / 190 (0.00%)
occurrences all number	3	6	4	14	8	17	12	3	7	2	2	0
PSORIATIC ARTHROPATHY
subjects affected / exposed	21 / 423 (4.96%)	14 / 430 (3.26%)	20 / 429 (4.66%)	42 / 378 (11.11%)	20 / 366 (5.46%)	33 / 366 (9.02%)	15 / 177 (8.47%)	10 / 178 (5.62%)	33 / 443 (7.45%)	2 / 188 (1.06%)	13 / 423 (3.07%)	5 / 190 (2.63%)
occurrences all number	21	16	22	61	24	46	19	12	42	2	14	5
Infections and infestations
LATENT TUBERCULOSIS
subjects affected / exposed	1 / 423 (0.24%)	1 / 430 (0.23%)	1 / 429 (0.23%)	22 / 378 (5.82%)	4 / 366 (1.09%)	19 / 366 (5.19%)	17 / 177 (9.60%)	8 / 178 (4.49%)	5 / 443 (1.13%)	0 / 188 (0.00%)	2 / 423 (0.47%)	0 / 190 (0.00%)
occurrences all number	1	1	1	22	4	19	17	8	5	0	2	0
BRONCHITIS
subjects affected / exposed	33 / 423 (7.80%)	28 / 430 (6.51%)	13 / 429 (3.03%)	27 / 378 (7.14%)	12 / 366 (3.28%)	16 / 366 (4.37%)	16 / 177 (9.04%)	6 / 178 (3.37%)	25 / 443 (5.64%)	6 / 188 (3.19%)	10 / 423 (2.36%)	3 / 190 (1.58%)
occurrences all number	39	30	14	33	15	18	19	6	32	6	10	3
COVID-19
subjects affected / exposed	0 / 423 (0.00%)	0 / 430 (0.00%)	0 / 429 (0.00%)	132 / 378 (34.92%)	51 / 366 (13.93%)	106 / 366 (28.96%)	57 / 177 (32.20%)	29 / 178 (16.29%)	117 / 443 (26.41%)	1 / 188 (0.53%)	0 / 423 (0.00%)	1 / 190 (0.53%)
occurrences all number	0	0	0	150	52	119	67	30	132	1	0	1
HERPES ZOSTER
subjects affected / exposed	16 / 423 (3.78%)	10 / 430 (2.33%)	2 / 429 (0.47%)	29 / 378 (7.67%)	21 / 366 (5.74%)	8 / 366 (2.19%)	12 / 177 (6.78%)	10 / 178 (5.62%)	9 / 443 (2.03%)	4 / 188 (2.13%)	3 / 423 (0.71%)	10 / 190 (5.26%)
occurrences all number	17	10	2	30	21	8	13	10	9	4	3	11
ORAL HERPES
subjects affected / exposed	28 / 423 (6.62%)	11 / 430 (2.56%)	10 / 429 (2.33%)	9 / 378 (2.38%)	8 / 366 (2.19%)	9 / 366 (2.46%)	4 / 177 (2.26%)	5 / 178 (2.81%)	7 / 443 (1.58%)	2 / 188 (1.06%)	4 / 423 (0.95%)	2 / 190 (1.05%)
occurrences all number	43	13	14	10	19	15	5	5	10	2	4	2
NASOPHARYNGITIS
subjects affected / exposed	45 / 423 (10.64%)	36 / 430 (8.37%)	43 / 429 (10.02%)	38 / 378 (10.05%)	24 / 366 (6.56%)	31 / 366 (8.47%)	15 / 177 (8.47%)	9 / 178 (5.06%)	36 / 443 (8.13%)	7 / 188 (3.72%)	21 / 423 (4.96%)	16 / 190 (8.42%)
occurrences all number	52	49	56	54	27	46	22	11	46	10	24	18
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	72 / 423 (17.02%)	67 / 430 (15.58%)	53 / 429 (12.35%)	56 / 378 (14.81%)	40 / 366 (10.93%)	42 / 366 (11.48%)	25 / 177 (14.12%)	15 / 178 (8.43%)	49 / 443 (11.06%)	13 / 188 (6.91%)	34 / 423 (8.04%)	11 / 190 (5.79%)
occurrences all number	100	92	63	82	52	60	48	18	62	16	37	13
URINARY TRACT INFECTION
subjects affected / exposed	30 / 423 (7.09%)	26 / 430 (6.05%)	18 / 429 (4.20%)	41 / 378 (10.85%)	21 / 366 (5.74%)	26 / 366 (7.10%)	15 / 177 (8.47%)	12 / 178 (6.74%)	25 / 443 (5.64%)	4 / 188 (2.13%)	10 / 423 (2.36%)	9 / 190 (4.74%)
occurrences all number	42	37	21	64	38	32	18	18	37	6	10	14

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

03 Mar 2017

Amendment 1 Key updates included: Title Page (Section 1.0) updated to provide current sponsor/emergency contact details with the country code; Section 1.2, Synopsis, to ensure consistent timing for hand and feet x-ray assessments and define inadequate MTX response for Japan; Section 5.2.1 and 5.2.2 addressed inclusion and exclusion criteria, removing duplicates and specifying MTX response; Table 2 updated clinical laboratory tests to require necessary tests for Japanese subjects with positive hepatitis markers, with clarifications on protocol deviation reporting; Updates to Section 5.3.1.1 ensured hepatitis screening for Japanese subjects; Section 6.1.5 added the country code to contacts for serious adverse event reporting; Section 9.3 clarified procedures on subject withdrawal concerning optional exploratory samples; and Appendix C updated the study activities table regarding hand/foot x-ray timing, footnotes on frequency, and protocol deviation reporting, ensuring required testing for Japanese subjects with hepatitis markers.

30 Jun 2017

Amendment 2 Key updates included: Section 1.0, added ABT-494's generic name and clarified Sponsor distinctions; Section 1.2, revised objectives, methodology, and evaluation criteria for efficacy and safety; Inclusion and exclusion criteria updates addressed specific dosages and testing requirements for China and Taiwan; Clarifications in the study design included criteria for subject non-responders, stratification, treatment modifications, and re-screening procedures; Changes in Section 5.2 entailed electrolyte criteria, prohibiting certain therapies, and refining HBV testing for specific regions; Contraceptive and pregnancy test clarifications were made alongside informed consent amendments; Section 5.3 procedures addressed ECG, CXR, and TB testing, and Table 2 and Figure 2 refined laboratory test requirements and HBV testing protocols; and Stratification clarifications continued across subject treatment assignments and analyses, along with updates on adverse event monitoring guidelines; Section 8 revisions involved laboratory and pharmacokinetic analysis adjustments, sample size determination, and randomization processes; and Appendices C, D, and E reflected updated follow-up requirements, exploratory sample guidelines, and the removal of outdated criteria.

22 Mar 2018

Amendment 3 Key updates included: Administrative changes and updated Sponsor information for non-EU countries; Cyclosporine is included as a qualifying DMARD for inadequate response in PsA treatment; The study design clarified non-replacement of withdrawn subjects and cessation of annual TB testing post-drug discontinuation; Inclusion criteria incorporated new guidelines for pregnancy testing, contraception, and PsA treatments; Exclusion criteria specified conditions for enrollment in non-interventional studies, prohibited certain therapies before Baseline, and clarified rules on pregnancy and other conditions; Background therapy stability is preferred but flexible for ensuring safety; Inhaled marijuana is excluded prior to Baseline due to infection risks; Contraception requirements for males were removed based on safety data; Study procedures clarified TB and hepatitis testing, pregnancy testing, and investigator assessments; Recommended to align AESI updates with recent studies on adverse events; Protocol deviations, efficacy variables, and analyses were updated to clarify methods and ensure accurate data interpretation.

11 Oct 2019

Amendment 4 Key updates included: Administrative changes; Inclusion of Cyclosporine in the methodology and study design sections as a therapy for inadequate response; Updatesd to ensure that Hong Kong is identified as part of China; Efficacy measures, such as FACIT-F and PsARC, were revised to match revised power calculations and endpoint descriptions; Abbreviations, safety information regarding thromboembolic events, and exclusion criteria were clarified; Permitted therapies and drug accountability guidelines were revised, aligning with new advisory information, including the discontinuation of male contraception recommendations due to updated safety findings; Requirements for skin biopsies were removed due to low enrollment likelihoods; ECG procedures and TB testing clarifications were streamlined, ensuring accurate safety evaluations; Toxicity management now included guidelines for herpes zoster and muscle-related symptoms, adjusted to match Rinvoq® labeling; Amendments to laboratory data assessment methodologies categorized results according to the National Cancer Institute's CTCAE grades; and Adjustments were made to appendices to align with these protocol updates, amending signatory lists and aligning optional sample instructions.

11 Dec 2019

Amendment 5 Key updates included: Changes to personnel contact information in Sections 1.0 and 6.1.5 to ensure the correct points of contact for the Sponsor and reporting of serious adverse events or malignancy; In Section 1.2, the evaluation criteria for efficacy was adjusted, emphasizing the resolution of enthesitis and dactylitis as more clinically significant outcomes than changes from Baseline, modifications were intended to enhance the clinical relevance and power calculations for the trial's multiplicity adjusted endpoints; Section 5.2.3.2 was updated to maintain participant safety by limiting the corticosteroid dosage to a maximum of prednisone ≤10 mg/day, as outlined in the inclusion criteria; Additionally, Section 5.3.3.2 was updated to align with the enhancements in evaluating enthesitis and dactylitis; To address concerns related to thrombosis risks associated with the JAK inhibitor class, Sections 5.4.1 and 6.1.7 incorporated additional safety precautions.

15 May 2020

Amendment 6 Key updates included: Extending the clinical trial duration by two years, adding extra timepoints for hands and feet x-rays to gather long-term safety and efficacy data for upadacitinib in treating PsA; Updates included personnel contact information and administrative changes; Protocol flexibility during emergencies or pandemics was improved by allowing the use of local laboratories and direct-to-patient drug shipments; Dispensing dosing diaries beyond Week 140 were deemed unnecessary, as compliance is tracked through the IRT system; Telephone interviews for patient-reported outcomes were added, ensuring data collection continuity during emergencies; TB testing guidelines were refined for consistency and clarity, minimizing unnecessary chest x-rays; Appendices were updated to reflect the extended study, detailing additional evaluation points for physical exams, pregnancy tests, and patient questionnaires; HBV DNA PCR testing was allowed during unscheduled visits; and Footnotes now stipulate that questionnaires EQ-5D-5L and WPAI will be every six months post-Week 152 instead of quarterly, maintaining scientific integrity while reducing participant burden.

30 Jan 2021

Amendment 7 Key updates included: Administrative changes; replacing "ABT-494" with the generic name "upadacitinib."; Subjects in Period 2 on a 30 mg QD dosage will switch to 15 mg QD to align with optimal dosing recommendations; Extension of study duration, and safety information about embryofetal risks was updated; Clarifications were added to prevent confounding data during discontinuation visits; South Korea was added in HBV-DNA PCR testing requirements; Flexibility was introduced for study procedures, allowing remote or delayed assessments during emergencies or pandemics; New guidelines were added for handling gastrointestinal perforations, COVID-19-related interruptions, and hematological toxicity; Amendments allowed remote monitoring, virtual consent processes, and specific data collection for COVID-19 impacts; Names of protocol signatories and vendors were updated, and footnotes re-sequenced to ensure protocol integrity.

20 Dec 2023

Amendment 8 Key updates included: Administrative updates and reinstating paper diary cards in China; Title page revised to include an EU-focused sponsor statement; Information from the ORAL Surveillance study, concerning another JAK inhibitor, informed current study benefits and risks, including upadacitinib’s effects on COVID-19; Provisions were made for follow-up flexibility with phone calls and exemptions for subjects transitioning to commercial upadacitinib or adalimumab; A new section outlined treatment post-study per CTTP directives; Prohibited therapy list was expanded, distinguishing live vaccines' replicative capabilities, and updates to lab testing guidelines include changes for South Korea and revised menopause criteria; Adverse event management added new criteria such as serious hypersensitivity, cardiovascular events, and ECG changes for discontinuation; Protocol deviations updated contact information and consent protocols; Toxicity management guidelines were clarified, incorporating COVID-19 measures, discontinuation requirements, and elective surgery protocols, alongside updates for AST/ALT and creatinine metrics; A new adjudication committee for gastrointestinal perforations was established; The study completion definition was refined to align with CTTP—a directive ensuring protocol integrity; and Appendices were reorganized, updating protocol signatories, footnotes for clarity on interventions, and follow-up call flexibility.

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

Primary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

Secondary: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

Secondary: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

Secondary: Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16

Secondary: Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16

Secondary: Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16

Secondary: Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16

Secondary: Change From Baseline in Modified PsA Total Sharp/Van Der Heijde Score (mTSS) at Week 24

Secondary: Change From Baseline in Modified PsA Total Sharp/Van Der Heijde Score (mTSS) at Week 24

Secondary: Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24

Secondary: Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24

Secondary: Percentage of Participants With Resolution of Enthesitis at Week 24

Secondary: Percentage of Participants With Resolution of Enthesitis at Week 24

Secondary: Percentage of Participants With an ACR20 Response at Week 12 - Non-inferiority Versus Adalimumab

Secondary: Percentage of Participants With an ACR20 Response at Week 12 - Non-inferiority Versus Adalimumab

Secondary: Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12

Secondary: Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12

Secondary: Percentage of Participants With an ACR20 Response at Week 12 - Superiority Versus Adalimumab

Secondary: Percentage of Participants With an ACR20 Response at Week 12 - Superiority Versus Adalimumab

Secondary: Percentage of Participants With Resolution of Dactylitis at Week 24

Secondary: Percentage of Participants With Resolution of Dactylitis at Week 24

Secondary: Change From Baseline in Patient's Assessment of Pain - Superiority Versus Adalimumab

Secondary: Change From Baseline in Patient's Assessment of Pain - Superiority Versus Adalimumab

Secondary: Change From Baseline in HAQ-DI - Superiority Versus Adalimumab

Secondary: Change From Baseline in HAQ-DI - Superiority Versus Adalimumab

Secondary: Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire at Week 16

Secondary: Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire at Week 16

Secondary: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12

Secondary: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12

Secondary: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12

Secondary: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12

Secondary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2

Secondary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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