Trial Outcomes & Findings for Basic Documentation of Adalimumab (Humira) in Patients With Ankylosing Spondylitis (AS) (NCT NCT01079182)

Last Updated: 2015-07-09

Results Overview

The BASDAI was a six question, participant-reported measure of overall disease activity that probed the level of fatigue, neck/back/hip pain, peripheral joint swelling and pain, localized tenderness, as well as morning stiffness severity and duration. It was scored on a numerical rating scale that ranged from 0 (no symptoms) to 10 (severe symptoms), and the minimum clinically important difference (MCID) was 1.0. The final BASDAI score was calculated using the following equation, in which 01 - 06 represents the question number: (BASDAI01 + BASDAI02 + BASDAI03 + BASDAI04 + BASDAI05/2 + BASDAI06\*1.25/2)/5. The scale for question 6 was reduced to 0-8 since BASDAI06 was multiplied by 1.25. Data are reported as the mean change total score from baseline (Month 0).

Recruitment status

COMPLETED

Target enrollment

4681 participants

Primary outcome timeframe

At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Results posted on

2015-07-09

Participant Flow

Participant milestones

Participant milestones
Measure	Ankylosing Spondylitis Participants with ankylosing spondylitis
Overall Study STARTED	4681
Overall Study COMPLETED	1962
Overall Study NOT COMPLETED	2719

Reasons for withdrawal

Reasons for withdrawal
Measure	Ankylosing Spondylitis Participants with ankylosing spondylitis
Overall Study Lost to Follow-up	1634
Overall Study Adverse Drug Reaction (ADR)	261
Overall Study Lack of Efficacy	514
Overall Study ADR and Lack of Effectiveness	39
Overall Study Reasons not Evaluated	271

Baseline Characteristics

Basic Documentation of Adalimumab (Humira) in Patients With Ankylosing Spondylitis (AS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ankylosing Spondylitis n=4681 Participants Participants with ankylosing spondylitis
Age, Continuous	43.1 Years STANDARD_DEVIATION 12.1 • n=93 Participants
Gender Female	1620 Participants n=93 Participants
Gender Male	3060 Participants n=93 Participants
Duration of Ankylosing Spondylitis (AS) Symptoms	14.4 Years STANDARD_DEVIATION 10.8 • n=93 Participants
Human Leukocyte Antigen (HLA) B27 Positive Status	84.4 Percentage of participants n=93 Participants

PRIMARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3756 Participants Participants with ankylosing spondylitis
Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Change from Baseline at Month 3 (N=3575)	-2.0 BASDAI score Standard Deviation 2.0
Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Baseline	5.5 BASDAI score Standard Deviation 1.9
Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Change from Baseline at Month 6 (N=3181)	-2.1 BASDAI score Standard Deviation 2.1
Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Change from Baseline at Month 9 (N=2828)	-2.2 BASDAI score Standard Deviation 2.2
Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Change from Baseline at Month 12 (N=2585)	-2.3 BASDAI score Standard Deviation 2.2
Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Change from Baseline at Month 18 (N=2169)	-2.3 BASDAI score Standard Deviation 2.3
Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score Change from Baseline at Month 24 (N=1799)	-2.3 BASDAI score Standard Deviation 2.3

PRIMARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

The BASFI was a ten question, participant-reported measure that evaluated physical function. Each question was scored on a numerical rating scale that ranged from 0 (no functional impairment) to 10 (maximal impairment), and the MCID was 0.7. The mean of the ten questions was the total BASFI score. Data are reported as the mean change of total score from baseline (Month 0).

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3743 Participants Participants with ankylosing spondylitis
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score Baseline	4.9 BASFI score Standard Deviation 2.4
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score Change from Baseline at Month 3 (N=3565)	-1.4 BASFI score Standard Deviation 1.9
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score Change from Baseline at Month 6 (N=3180)	-1.5 BASFI score Standard Deviation 2.0
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score Change from Baseline at Month 9 (N=2821)	-1.6 BASFI score Standard Deviation 2.1
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score Change from Baseline at Month 12 (N=2572)	-1.6 BASFI score Standard Deviation 2.1
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score Change from Baseline at Month 18 (N=2160)	-1.7 BASFI score Standard Deviation 2.2
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score Change from Baseline at Month 24 (N=1793)	-1.7 BASFI score Standard Deviation 2.2

PRIMARY outcome

Timeframe: From signing of informed consent up to 24 months

Population: Safety analysis set: Participants who received at least one dose of adalimumab.

An adverse event/adverse experience was any reaction, side effect or other untoward event associated with the use of a drug in humans, whether or not the event was considered drug related. This included adverse events occurring from accidental or deliberate drug overdose, from drug abuse, or from drug withdrawal. Exacerbations of pre-existing conditions are also considered adverse events. Data presented are adverse events that are drug-related and are detailed in the adverse event section of this report.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=4681 Participants Participants with ankylosing spondylitis
Number of Participants With Drug-Related Adverse Events (AEs)	1099 Participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Peripheral joints were assessed by Tender Joint Counts (TJC) and Swollen Joint Counts (SJC), using pressure and joint manipulation during physical examination. Seventy-eight TJC and 76 SJC were evaluated and a score of 0 (not tender or swollen) or 1 (tender or swollen) was assigned for each joint with a higher total score indicating a greater number of involved joints.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3715 Participants Participants with ankylosing spondylitis
Mean Number of Involved Peripheral Joints TJC at Month 18 (N=2162)	1.5 Joints Standard Deviation 5.4
Mean Number of Involved Peripheral Joints TJC at Month 24 (N=1804)	1.2 Joints Standard Deviation 5.0
Mean Number of Involved Peripheral Joints SJC at Month 24 (N=1804)	0.4 Joints Standard Deviation 2.3
Mean Number of Involved Peripheral Joints TJC at Baseline	3.1 Joints Standard Deviation 7.2
Mean Number of Involved Peripheral Joints TJC at Month 3 (N=3576)	1.8 Joints Standard Deviation 6.0
Mean Number of Involved Peripheral Joints TJC at Month 6 (N=3172)	1.6 Joints Standard Deviation 5.6
Mean Number of Involved Peripheral Joints TJC at Month 9 (N=2821)	1.6 Joints Standard Deviation 5.7
Mean Number of Involved Peripheral Joints TJC at Month 12 (N=2583)	1.5 Joints Standard Deviation 6.1
Mean Number of Involved Peripheral Joints SJC at Baseline	1.3 Joints Standard Deviation 4.5
Mean Number of Involved Peripheral Joints SJC at Month 3 (N=3576)	0.7 Joints Standard Deviation 3.4
Mean Number of Involved Peripheral Joints SJC at Month 6 (N=3172)	0.6 Joints Standard Deviation 3.0
Mean Number of Involved Peripheral Joints SJC at Month 9 (N=2821)	0.5 Joints Standard Deviation 2.9
Mean Number of Involved Peripheral Joints SJC at Month 12 (N=2583)	0.4 Joints Standard Deviation 2.3
Mean Number of Involved Peripheral Joints SJC at Month 18 (N=2162)	0.5 Joints Standard Deviation 3.1

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Extraspinal manifestations (enthesitis, dactylitis, uveitis, psoriasis, and Inflammatory Bowel Disease (IBD)) were assessed by investigators and reported on the basis of their clinical evaluation and participant records.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3756 Participants Participants with ankylosing spondylitis
Percentage of Participants With Extraspinal Manifestations Psoriasis at Month 9 (N=2858)	2.6 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Psoriasis at Month 12 (N=2603)	2.5 Percentage of participants
Percentage of Participants With Extraspinal Manifestations IBD at Month 12 (N=2603)	1.7 Percentage of participants
Percentage of Participants With Extraspinal Manifestations IBD at Month 18 (N=2183)	1.4 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Enthesitis at Baseline	13.6 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Enthesitis at Month 3 (N=3616)	5.6 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Enthesitis at Month 6 (N=3216)	3.7 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Enthesitis at Month 9 (N=2858)	4.1 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Enthesitis at Month 12 (N=2603)	4.5 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Enthesitis at Month 18 (N=2183)	3.5 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Enthesitis at Month 24 (N=1823)	3.4 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Dactylitis at Baseline	5.4 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Dactylitis at Month 3 (N=3616)	2.4 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Dactylitis at Month 6 (N=3216)	1.6 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Dactylitis at Month 9 (N=2858)	1.3 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Dactylitis at Month 12 (N=2603)	1.6 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Dactylitis at Month 18 (N=2183)	1.3 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Dactylitis at Month 24 (N=1823)	1.9 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Uveitis at Baseline	3.3 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Uveitis at Month 3 (N=3616)	1.1 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Uveitis at Month 6 (N=3216)	0.9 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Uveitis at Month 9 (N=2858)	0.7 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Uveitis at Month 12 (N=2603)	0.5 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Uveitis at Month 18 (N=2183)	0.5 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Uveitis at Month 24 (N=1823)	0.7 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Psoriasis at Baseline	5.4 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Psoriasis at Month 3 (N=3616)	2.9 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Psoriasis at Month 6 (N=3216)	2.7 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Psoriasis at Month 18 (N=2183)	2.3 Percentage of participants
Percentage of Participants With Extraspinal Manifestations Psoriasis at Month 24 (N=1823)	2.8 Percentage of participants
Percentage of Participants With Extraspinal Manifestations IBD at Baseline	4.4 Percentage of participants
Percentage of Participants With Extraspinal Manifestations IBD at Month 3 (N=3616)	2.6 Percentage of participants
Percentage of Participants With Extraspinal Manifestations IBD at Month 6 (N=3216)	1.8 Percentage of participants
Percentage of Participants With Extraspinal Manifestations IBD at Month 9 (N=2858)	1.9 Percentage of participants
Percentage of Participants With Extraspinal Manifestations IBD at Month 24 (N=1823)	1.9 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Plasma concentrations of ESR were assessed as a marker of systemic inflammation that provided insights into the overall anti-inflammatory effect of rheumatologic therapies.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3514 Participants Participants with ankylosing spondylitis
Mean Erythrocyte Sedimentation Rate (ESR) Baseline	26.8 mm/hour Standard Deviation 21.6
Mean Erythrocyte Sedimentation Rate (ESR) At Month 3 (N=3231)	12.9 mm/hour Standard Deviation 14.1
Mean Erythrocyte Sedimentation Rate (ESR) At Month 6 (N=2888)	13.3 mm/hour Standard Deviation 15.1
Mean Erythrocyte Sedimentation Rate (ESR) At Month 9 (N=2540)	13.6 mm/hour Standard Deviation 15.3
Mean Erythrocyte Sedimentation Rate (ESR) At Month 12 (N=2288)	13.3 mm/hour Standard Deviation 14.1
Mean Erythrocyte Sedimentation Rate (ESR) At Month 18 (N=1932)	13.3 mm/hour Standard Deviation 13.6
Mean Erythrocyte Sedimentation Rate (ESR) At Month 24 (N=1627)	14.0 mm/hour Standard Deviation 13.7

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Plasma concentrations of CRP were assessed as a marker of systemic inflammation that provided insights into the overall anti-inflammatory effect of rheumatologic therapies.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3638 Participants Participants with ankylosing spondylitis
Mean Plasma Concentrations of C-Reactive Protein (CRP) Baseline	17.1 mg/L Standard Deviation 21.8
Mean Plasma Concentrations of C-Reactive Protein (CRP) At Month 3 (N=3277)	6.2 mg/L Standard Deviation 11.0
Mean Plasma Concentrations of C-Reactive Protein (CRP) At Month 6 (N=2934)	6.5 mg/L Standard Deviation 13.4
Mean Plasma Concentrations of C-Reactive Protein (CRP) At Month 9 (N=2601)	6.3 mg/L Standard Deviation 11.9
Mean Plasma Concentrations of C-Reactive Protein (CRP) At Month 12 (N=2344)	6.0 mg/L Standard Deviation 11.9
Mean Plasma Concentrations of C-Reactive Protein (CRP) At Month 18 (N=2004)	5.5 mg/L Standard Deviation 9.1
Mean Plasma Concentrations of C-Reactive Protein (CRP) At Month 24 (N=1687)	5.8 mg/L Standard Deviation 9.5

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

The BAS-G was a participant-reported instrument with two items. In the first item, the participant rated the effect of their disease over the last week, and in the second item, the participant rated the effect of their disease over the previous 6 months. Each item of the BAS-G was scored on a scale ranging from 0 (no effect) to 10 (very severe effect). The mean of the two scores was the total BAS-G score and the MCID was 1.5.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3734 Participants Participants with ankylosing spondylitis
Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score Baseline	6.7 BAS-G score Standard Deviation 2.0
Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score At Month 3 (N=3562)	4.8 BAS-G score Standard Deviation 2.2
Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score At Month 6 (N=3178)	4.1 BAS-G score Standard Deviation 2.4
Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score At Month 9 (N=2832)	3.8 BAS-G score Standard Deviation 2.4
Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score At Month 12 (N=2574)	3.6 BAS-G score Standard Deviation 2.4
Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score At Month 18 (N=2162)	3.5 BAS-G score Standard Deviation 2.4
Mean Bath Ankylosing Spondylitis-Global (BAS-G) Score At Month 24 (N=1796)	3.4 BAS-G score Standard Deviation 2.4

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Global Assessment of Disease Activity was a participant-reported measure that evaluated disease activity. It was scored on a scale that ranged from 0 to 10; lower scores indicated better patient status.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3744 Participants Participants with ankylosing spondylitis
Mean Global Assessment of Disease Activity Score Baseline	6.5 Score on scale Standard Deviation 1.7
Mean Global Assessment of Disease Activity Score At Month 3 (N=3574)	3.1 Score on scale Standard Deviation 2.1
Mean Global Assessment of Disease Activity Score At Month 6 (N=3174)	2.8 Score on scale Standard Deviation 2.1
Mean Global Assessment of Disease Activity Score At Month 9 (N=2831)	2.6 Score on scale Standard Deviation 2.0
Mean Global Assessment of Disease Activity Score At Month 12 (N=2574)	2.4 Score on scale Standard Deviation 1.9
Mean Global Assessment of Disease Activity Score At Month 18 (N=2161)	2.3 Score on scale Standard Deviation 1.9
Mean Global Assessment of Disease Activity Score At Month 24 (N=1805)	2.2 Score on scale Standard Deviation 1.9

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Using the BASDAI questionnaire, participants assessed the overall level of fatigue/tiredness experienced by him/her. It was scored on a numerical rating scale from 0 (no symptoms) to 10 (severe symptoms).

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3756 Participants Participants with ankylosing spondylitis
Mean Participant Fatigue Score Baseline	5.9 Score on scale Standard Deviation 2.3
Mean Participant Fatigue Score At Month 3 (N=3585)	4.3 Score on scale Standard Deviation 2.5
Mean Participant Fatigue Score At Month 6 (N=3189)	4.2 Score on scale Standard Deviation 2.5
Mean Participant Fatigue Score At Month 9 (N=2837)	4.0 Score on scale Standard Deviation 2.5
Mean Participant Fatigue Score At Month 12 (N=2591)	3.9 Score on scale Standard Deviation 2.5
Mean Participant Fatigue Score At Month 18 (N=2174)	3.8 Score on scale Standard Deviation 2.4
Mean Participant Fatigue Score At Month 24 (N=1803)	3.8 Score on scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Using the BASDAI questionnaire, participants assessed the overall level of AS neck, back or hip pain experienced by him/her. It was scored on a numerical rating scale from 0 (no symptoms) to 10 (severe symptoms).

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3756 Participants Participants with ankylosing spondylitis
Mean Participant Pain Score Baseline	6.7 Score on scale Standard Deviation 2.3
Mean Participant Pain Score At Month 3 (N=3586)	4.0 Score on scale Standard Deviation 2.6
Mean Participant Pain Score At Month 6 (N=3191)	3.9 Score on scale Standard Deviation 2.6
Mean Participant Pain Score At Month 9 (N=2839)	3.8 Score on scale Standard Deviation 2.6
Mean Participant Pain Score At Month 12 (N=2589)	3.7 Score on scale Standard Deviation 2.5
Mean Participant Pain Score At Month 18 (N=2173)	3.5 Score on scale Standard Deviation 2.5
Mean Participant Pain Score At Month 24 (N=1804)	3.5 Score on scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Morning stiffness was a participant-reported assessment. The number of participants with morning stiffness were assessed at each visit.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3756 Participants Participants with ankylosing spondylitis
Percentage of Participants With Morning Stiffness At Month 9 (N=2835)	78.8 Percentage of participants
Percentage of Participants With Morning Stiffness Baseline	95.4 Percentage of participants
Percentage of Participants With Morning Stiffness At Month 3 (N=3582)	81.8 Percentage of participants
Percentage of Participants With Morning Stiffness At Month 6 (N=3186)	79.9 Percentage of participants
Percentage of Participants With Morning Stiffness At Month 12 (N=2589)	77.6 Percentage of participants
Percentage of Participants With Morning Stiffness At Month 18 (N=2173)	77.6 Percentage of participants
Percentage of Participants With Morning Stiffness At Month 24 (N=1802)	77.8 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Participants accessed the duration of morning stiffness in 15 minute intervals from 0 to 2 hours. Data are reported as the mean duration of morning stiffness ± standard deviation.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3756 Participants Participants with ankylosing spondylitis
Mean Duration of Morning Stiffness Baseline	56.7 minutes Standard Deviation 34.5
Mean Duration of Morning Stiffness At Month 3 (N=3582)	33.5 minutes Standard Deviation 30.7
Mean Duration of Morning Stiffness At Month 6 (N=3186)	31.3 minutes Standard Deviation 30.0
Mean Duration of Morning Stiffness At Month 9 (N=2835)	29.6 minutes Standard Deviation 28.7
Mean Duration of Morning Stiffness At Month 12 (N=2589)	28.6 minutes Standard Deviation 28.2
Mean Duration of Morning Stiffness At Month 18 (N=2173)	27.7 minutes Standard Deviation 27.4
Mean Duration of Morning Stiffness At Month 24 (N=1802)	27.4 minutes Standard Deviation 27.0

SECONDARY outcome

Timeframe: At 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

This is a four domain (participant global assessment of disease activity, assessment of spinal pain, assessment of function (BASFI), and assessment of duration/severity of morning stiffness (mean of BASDAI questions 5 and 6)), participant-reported assessment scored on a scale from 0 (best) to 10 (worst). To qualify for a 20% improvement, participants were required to have an improvement of greater than or equal to 20% and greater than or equal to 1 unit in at least 3 domains, and no worsening of greater than or equal to 20% and greater than or equal to 1 unit in the remaining domain. To achieve a 40% improvement, participants were required to have an improvement of greater than or equal to 40% and greater than or equal to 2 units in at least 3 domains, and no worsening at all in the remaining domain.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3349 Participants Participants with ankylosing spondylitis
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 20 Improvement at Month 3	57.9 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 20 Improvement at Month 6 (N=2989)	63.0 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 20 Improvement at Month 9 (N=2661)	64.3 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 20 Improvement at Month 12 (N=2419)	65.6 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 20 Improvement at Month 18 (N=2030)	66.9 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 20 Improvement at Month 24 (N=1688)	67.2 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 40 Improvement at Month 3	36.4 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 40 Improvement at Month 6 (N=2989)	40.1 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 40 Improvement at Month 9 (N=2661)	42.5 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 40 Improvement at Month 12 (N=2419)	43.7 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 40 Improvement at Month 18 (N=2030)	45.9 Percentage of participants
Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) Improvement Criteria ASAS 40 Improvement at Month 24 (N=1688)	46.8 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3731 Participants Participants with ankylosing spondylitis
Percentage of Participants Achieving ASAS Partial Remission Criteria Baseline	1.1 Percentage of participants
Percentage of Participants Achieving ASAS Partial Remission Criteria Month 3 (N=3537)	17.7 Percentage of participants
Percentage of Participants Achieving ASAS Partial Remission Criteria Month 6 (N=3128)	21.5 Percentage of participants
Percentage of Participants Achieving ASAS Partial Remission Criteria Month 9 (N=2785)	23.3 Percentage of participants
Percentage of Participants Achieving ASAS Partial Remission Criteria Month 12 (N=2535)	23.9 Percentage of participants
Percentage of Participants Achieving ASAS Partial Remission Criteria Month 18 (N=2132)	24.9 Percentage of participants
Percentage of Participants Achieving ASAS Partial Remission Criteria Month 24 (N=1782)	26.8 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

The impairment of daily activities was based on participant recall of events that occurred over the 4 weeks before the visit. Percentage of participants with impairment for 0, less than 7, 7 to 14, and greater than 14 days was assessed.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3654 Participants Participants with ankylosing spondylitis
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 0 Days at Baseline	23.0 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 0 Days at Month 3 (N=3496)	47.2 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 0 Days at Month 6 (N=3121)	52.6 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 0 Days at Month 9 (N=2793)	55.9 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 0 Days at Month 12 (N=2524)	57.1 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 0 Days at Month 18 (N=2130)	60.2 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 0 Days at Month 24 (N=1766)	60.9 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Less Than 7 Days at Baseline	28.5 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Less Than 7 Days at Month 3 (N=3496)	30.3 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Less Than 7 Days at Month 6 (N=3121)	28.5 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Less Than 7 Days at Month 9 (N=2793)	27.2 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Less Than 7 Days at Month 12 (N=2524)	27.2 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Less Than 7 Days at Month 18 (N=2130)	24.4 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Less Than 7 Days at Month 24 (N=1766)	24.0 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 7 to 14 Days at Baseline	23.4 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 7 to 14 Days at Month 3 (N=3496)	11.6 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 7 to 14 Days at Month 6 (N=3121)	9.9 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 7 to 14 Days at Month 9 (N=2793)	9.6 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 7 to 14 Days at Month 12 (N=2524)	8.9 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 7 to 14 Days at Month 18 (N=2130)	8.8 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks 7 to 14 Days at Month 24 (N=1766)	8.9 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Greater Than 14 Days at Baseline	25.1 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Greater Than 14 Days at Month 3 (N=3496)	11.0 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Greater Than 14 Days at Month 6 (N=3121)	9.0 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Greater Than 14 Days at Month 9 (N=2793)	7.3 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Greater Than 14 Days at Month 12 (N=2524)	6.8 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Greater Than 14 Days at Month 18 (N=2130)	6.6 Percentage of participants
Percentage of Participants With Impairment in Daily Activities During the Last 4 Weeks Greater Than 14 Days at Month 24 (N=1766)	6.1 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=2217 Participants Participants with ankylosing spondylitis
Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months Baseline	45.7 Percentage of participants
Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months At Month 3 (N=2082)	39.3 Percentage of participants
Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months At Month 6 (N=1870)	32.2 Percentage of participants
Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months At Month 9 (N=1673)	26.3 Percentage of participants
Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months At Month 12 (N=1549)	21.3 Percentage of participants
Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months At Month 18 (N=1331)	17.2 Percentage of participants
Percentage of Participants Who Missed Work Days Due to Ankylosing Spondylitis (AS) in the Previous 12 Months At Month 24 (N=1105)	14.2 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=2217 Participants Participants with ankylosing spondylitis
Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months Baseline	48.0 Days Standard Deviation 69.1
Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months At Month 3 (N=2082)	52.2 Days Standard Deviation 74.3
Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months At Month 6 (N=1870)	56.0 Days Standard Deviation 85.7
Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months At Month 9 (N=1673)	50.5 Days Standard Deviation 81.7
Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months At Month 12 (N=1549)	48.0 Days Standard Deviation 80.1
Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months At Month 18 (N=1331)	35.3 Days Standard Deviation 61.4
Mean Missed Work Days Due to Ankylosing Spondylitis in the Previous 12 Months At Month 24 (N=1105)	35.4 Days Standard Deviation 61.3

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3692 Participants Participants with ankylosing spondylitis
Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months Baseline	20.6 Percentage of participants
Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 3 (N=3521)	18.9 Percentage of participants
Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 6 (N=3134)	16.9 Percentage of participants
Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 9 (N=2798)	12.9 Percentage of participants
Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 12 (N=2538)	8.4 Percentage of participants
Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 18 (N=2133)	4.7 Percentage of participants
Percentage of Participants With In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 24 (N=1762)	3.8 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3692 Participants Participants with ankylosing spondylitis
Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months Baseline	16.0 Days Standard Deviation 14.7
Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 3 (N=3521)	15.1 Days Standard Deviation 12.6
Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 6 (N=3134)	16.3 Days Standard Deviation 21.5
Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 9 (N=2798)	17.2 Days Standard Deviation 26.4
Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 12 (N=2538)	18.8 Days Standard Deviation 33.9
Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 18 (N=2133)	17.7 Days Standard Deviation 12.4
Mean Days of In-Patient Hospitalization Due to Ankylosing Spondylitis in the Previous 12 Months At Month 24 (N=1762)	15.3 Days Standard Deviation 11.9

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3744 Participants Participants with ankylosing spondylitis
Percentage of Participants on Adalimumab Monotherapy Baseline	78.8 Percentage of participants
Percentage of Participants on Adalimumab Monotherapy At Month 3 (N=3591)	81.6 Percentage of participants
Percentage of Participants on Adalimumab Monotherapy At Month 6 (N=3202)	82.8 Percentage of participants
Percentage of Participants on Adalimumab Monotherapy At Month 9 (N=2848)	83.2 Percentage of participants
Percentage of Participants on Adalimumab Monotherapy At Month 12 (N=2598)	83.6 Percentage of participants
Percentage of Participants on Adalimumab Monotherapy At Month 18 (N=2179)	83.7 Percentage of participants
Percentage of Participants on Adalimumab Monotherapy At Month 24 (N=1816)	84.6 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3744 Participants Participants with ankylosing spondylitis
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Methotrexate at Month 24 (N=1816)	11.0 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Methotrexate at Baseline	13.0 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Methotrexate at Month 3 (N=3591)	11.9 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Methotrexate at Month 6 (N=3202)	11.9 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Methotrexate at Month 9 (N=2848)	11.6 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Methotrexate at Month 12 (N=2598)	11.5 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Methotrexate at Month 18 (N=2179)	11.6 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Sulfasalazine at Baseline	7.5 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Sulfasalazine at Month 3 (N=3591)	5.2 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Sulfasalazine at Month 6 (N=3202)	4.2 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Sulfasalazine at Month 9 (N=2848)	3.9 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Sulfasalazine at Month 12 (N=2598)	3.8 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Sulfasalazine at Month 18 (N=2179)	3.7 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Sulfasalazine at Month 24 (N=1816)	3.3 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Other DMARDs at Baseline	2.3 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Other DMARDs at Month 3 (N=3591)	1.9 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Other DMARDs at Month 6 (N=3202)	1.8 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Other DMARDs at Month 9 (N=2848)	2.0 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Other DMARDs at Month 12 (N=2598)	1.8 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Other DMARDs at Month 18 (N=2179)	1.6 Percentage of participants
Percentage of Participants With Concomitant Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs) Other DMARDs at Month 24 (N=1816)	1.5 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

Participants with concomitant pain relief/anti-inflammatory agents like analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, and systemic glucocorticoids were assessed during the study period.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3744 Participants Participants with ankylosing spondylitis
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Analgesics at Baseline	17.5 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Analgesics at Month 3 (N=3591)	12.4 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Analgesics at Month 6 (N=3202)	11.8 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Analgesics at Month 9 (N=2848)	11.1 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Analgesics at Month 12 (N=2598)	11.2 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Analgesics at Month 18 (N=2179)	10.1 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Analgesics at Month 24 (N=1816)	10.3 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents NSAIDs at Baseline	52.3 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents NSAIDs at Month 3 (N=3591)	36.1 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents NSAIDs at Month 6 (N=3202)	33.5 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents NSAIDs at Month 9 (N=2848)	31.4 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents NSAIDs at Month 12 (N=2598)	30.2 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents NSAIDs at Month 18 (N=2179)	31.3 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents NSAIDs at Month 24 (N=1816)	30.2 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents COX-2 Inhibitors at Baseline	21.4 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents COX-2 Inhibitors at Month 3 (N=3591)	16.5 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents COX-2 Inhibitors at Month 6 (N=3202)	15.4 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents COX-2 Inhibitors at Month 9 (N=2848)	15.0 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents COX-2 Inhibitors at Month 12 (N=2598)	14.5 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents COX-2 Inhibitors at Month 18 (N=2179)	14.0 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents COX-2 Inhibitors at Month 24 (N=1816)	13.3 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Systemic Glucocorticoids at Baseline	22.9 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Systemic Glucocorticoids at Month 3 (N=3591)	15.2 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Systemic Glucocorticoids at Month 6 (N=3202)	13.1 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Systemic Glucocorticoids at Month 9 (N=2848)	11.8 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Systemic Glucocorticoids at Month 12 (N=2598)	11.9 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Systemic Glucocorticoids at Month 18 (N=2179)	11.3 Percentage of participants
Percentage of Participants With Concomitant Pain Relief/Anti-Inflammatory Agents Systemic Glucocorticoids at Month 24 (N=1816)	11.0 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Month 0), 3, 6, 9, 12, 18, and 24 months

Population: Full analysis set: Participants with adequate data available for evaluation of effectiveness.

The mean equivalent dose of prednisolone was calculated based on the International Standard for comparison of different glucocorticoid products.

Outcome measures

Outcome measures
Measure	Ankylosing Spondylitis n=3744 Participants Participants with ankylosing spondylitis
Mean Equivalent Dose of Prednisolone Baseline	10.5 mg/day Standard Deviation 15.2
Mean Equivalent Dose of Prednisolone At Month 3 (N=3591)	6.6 mg/day Standard Deviation 5.0
Mean Equivalent Dose of Prednisolone At Month 6 (N=3202)	6.8 mg/day Standard Deviation 6.6
Mean Equivalent Dose of Prednisolone At Month 9 (N=2848)	6.4 mg/day Standard Deviation 6.1
Mean Equivalent Dose of Prednisolone At Month 12 (N=2598)	7.2 mg/day Standard Deviation 14.9
Mean Equivalent Dose of Prednisolone At Month 18 (N=2179)	6.0 mg/day Standard Deviation 7.0
Mean Equivalent Dose of Prednisolone At Month 24 (N=1816)	5.6 mg/day Standard Deviation 3.8

Adverse Events

Ankylosing Spondylitis

Serious events: 141 serious events

Other events: 1099 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ankylosing Spondylitis n=4681 participants at risk Participants with ankylosing spondylitis
Surgical and medical procedures Surgery	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Vascular bypass graft	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Adhesiolysis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Caecum operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Cardioversion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Cholecystectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Coronary revascularization	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Foot operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Gastric operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hernia repair	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hysterectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Kidney ablation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Meniscus operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Rehabilitation therapy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Salpingo-oophorectomy bilateral	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Shoulder operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Spinal operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Stent placement	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Therapeutic procedure	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Tonsillectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pneumonia	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hospitalization	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hip arthroplasty	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Knee arthroplasty	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Intervertebral disc operation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Cellulitis	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Acute tonsillitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Tuberculosis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Urinary tract infection	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Abscess limb	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Anal abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Arthritis bacterial	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Bronchitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Cytomegalovirus infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Fungal oesophagitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Gastroenteritis escherichia coli	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Gastrointestinal infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Herpes zoster	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Influenza	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pancreatitis bacterial	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Peritonsillar abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Postoperative wound infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pulmonary tuberculosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Respiratory tract infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Salmonellosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Sepsis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Sinusitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Stitch abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Systemic mycosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Arthralgia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Arthritis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Back pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Myositis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Osteitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Polyarthritis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Toe deformity	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Nausea	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Pancreatitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Tooth loss	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Diarrhoea	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Diverticular perforation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Diverticulum intestinal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Duodenitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Dysphagia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastric haemorrhage	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastritis erosive	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastrointestinal mucosal disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastrointestinal pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Haematochezia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Melaena	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Pancreatic mass	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Pancreatitis acute	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Periodontitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Peritoneal adhesions	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Subileus	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Vomiting	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Fall	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Post procedural complication	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Accident	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Ankle fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Dislocation of vertebra	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Foot fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Haemothorax	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Incisional hernia, obstructive	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Lower limb fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Meniscus lesion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Multiple injuries	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Post procedural fistula	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Road traffic accident	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Spinal fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Ureteric injury	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Acute myocardial infarction	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Cardiac failure	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Atrial fibrillation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Myocardial infarction	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Arrhythmia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Coronary artery disease	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Palpitations	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Sinus tachycardia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Pyrexia	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Abasia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Adhesion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Chest discomfort	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Chest pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Disease recurrence	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Performance status decreased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Dizziness	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Cerebrovascular accident	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Hypoaesthesia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Transient ischaemic attack	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Altered state of consciousness	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Aphasia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Convulsion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Disturbance in attention	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Hemiparesis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Hyperaesthesia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Multiple sclerosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Polyneuropathy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Sciatica	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Somnolence	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Psoriasis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Alopecia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dry skin	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Erythema	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Plantar erythema	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Pruritus	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Pustular psoriasis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Hypertension	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Aortic aneurysm	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Deep vein thrombosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Hypertensive crisis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Thrombosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Nasal turbinate hypertrophy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Body temperature increased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Hepatic enzyme increased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Laboratory test abnormal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Laparoscopy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Weight decreased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seminoma	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Depression	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Mental disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Panic disorder with agoraphobia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Suicidal ideation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Lymphadenitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Lymphadenopathy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Thrombocytopenia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Cholelithiasis	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Cholecystitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Hepatocellular damage	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Congenital, familial and genetic disorders Chondrodystrophy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Congenital, familial and genetic disorders Factor V deficiency	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Conjunctivitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Visual disturbance	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Renal colic	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Nephrolithiasis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Adnexa uteri cyst	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Breast mass	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Ear and labyrinth disorders Sudden hearing loss	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Death	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.

Other adverse events

Other adverse events
Measure	Ankylosing Spondylitis n=4681 participants at risk Participants with ankylosing spondylitis
Investigations Antinuclear antibody increased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Biopsy breast normal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Drug ineffective	4.5% 210/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Influenza like illness	1.1% 50/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Pyrexia	0.70% 33/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site erythema	0.68% 32/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Fatigue	0.58% 27/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site pruritus	0.32% 15/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site irritation	0.26% 12/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site reaction	0.26% 12/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Oedema peripheral	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site pain	0.17% 8/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site swelling	0.17% 8/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Impaired healing	0.15% 7/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Drug intolerance	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Malaise	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Pain	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Chills	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders General physical health deterioration	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Inflammation	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Asthenia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Chest discomfort	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Chest pain	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Condition aggravated	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site rash	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site warmth	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Local swelling	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Mucosal dryness	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Sensation of foreign body	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Swelling	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Abasia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Adverse event	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Cyst	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Feeling abnormal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Feeling cold	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Feeling hot	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Gait disturbance	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Induration	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site discharge	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site induration	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site inflammation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Injection site urticaria	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Mucosal haemorrhage	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Mucosal inflammation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Performance status decreased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
General disorders Tenderness	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Bronchitis	0.98% 46/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Upper respiratory tract infection	0.98% 46/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Nasopharyngitis	0.79% 37/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Infection	0.77% 36/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Sinusitis	0.70% 33/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Respiratory tract infection	0.51% 24/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Herpes zoster	0.32% 15/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Gastrointestinal infection	0.26% 12/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Infection in an immunocompromised host	0.26% 12/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Rash pustular	0.23% 11/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Otitis media	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pneumonia	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Urinary tract infection	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Acute tonsillitis	0.19% 9/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Cystitis	0.19% 9/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Oral herpes	0.19% 9/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Rhinitis	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Tonsillitis	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Erysipelas	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Folliculitis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Furuncle	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Herpes virus infection	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Laryngitis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pharyngitis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pyelonephritis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Influenza	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Viral infection	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Vulvovaginal mycotic infection	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Abscess	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Bronchopneumonia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Chronic sinusitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Diverticulitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Ear infection	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Gastroenteritis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Paronychia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Respiratory tract infection viral	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Skin infection	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Tooth infection	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Abdominal wall abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Abscess jaw	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Anal abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Anogenital warts	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Body tinea	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Borrelia infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Bronchitis bacterial	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Campylobacter intestinal infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Conjunctivitis infective	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Eczema impetiginous	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Erythema infectiosum	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Fungal skin infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Gastrointestinal fungal infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Genital abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Genitourinary tract infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Gingival infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Groin abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Infectious mononucleosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Intervertebral discitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Latent tuberculosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Legionella infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Molluscum contagiosum	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Onychomycosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Oropharyngitis fungal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Parotitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pertussis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Postoperative wound infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Pseudofolliculitis barbae	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Puncture site abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Scarlet fever	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Sepsis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Sialoadenitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Subcutaneous abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Tinea infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Tinea pedis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Tooth abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Urosepsis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Vaginal abscess	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Varicella	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Infections and infestations Viral upper respiratory tract infection	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash	0.75% 35/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Psoriasis	0.64% 30/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Pruritus	0.56% 26/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Pustular psoriasis	0.41% 19/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Erythema	0.38% 18/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Alopecia	0.28% 13/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.26% 12/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Urticaria	0.19% 9/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.17% 8/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Night sweats	0.15% 7/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin exfoliation	0.15% 7/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Acne	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dry skin	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Eczema	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Pruritus generalised	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash papular	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin reaction	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Drug eruption	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash generalised	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash pruritic	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin disorder	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Blister	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Erythema multiforme	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dermatitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dermatitis psoriasiform	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dyshidrosis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Neurodermatitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Acrodermatitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Dermal cyst	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Erythema annulare	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Heat rash	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Hypoaesthesia facial	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Intertrigo	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Nail bed inflammation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Onychoclasis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Onycholysis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Parapsoriasis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Pigmentation disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Pityriasis rosea	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash erythematous	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rash macular	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Rosacea	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin burning sensation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin fibrosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin lesion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin nodule	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin odour abnormal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin swelling	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Skin warm	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Swelling face	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Skin and subcutaneous tissue disorders Urticaria generalised	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Diarrhoea	0.49% 23/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Nausea	0.36% 17/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Periodontitis	0.15% 7/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Abdominal pain upper	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastrointestinal pain	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Vomiting	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastritis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Tooth disorder	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Abdominal discomfort	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Abdominal pain	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Abdominal pain lower	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Colitis	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Abdominal distension	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Aphthous stomatitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Dental caries	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Dyspepsia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Dysphagia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gingival bleeding	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Haematochezia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Hypoaesthesia oral	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Oral discomfort	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Reflux oesophagitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Stomatitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Anal fissure	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Ascites	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Crohn's disease	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Diverticulum	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Dry mouth	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Frequent bowel movements	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastric ulcer	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Gastroduodenitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Glossodynia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Haemorrhoids	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Hiatus hernia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Intestinal haemorrhage	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Lip blister	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Odynophagia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Oedema mouth	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Oral mucosal blistering	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Oral mucosal disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Proctitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Retching	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Salivary gland disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Stomach discomfort	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Tongue black hairy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Gastrointestinal disorders Toothache	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Headache	0.79% 37/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Dizziness	0.41% 19/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Paraesthesia	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Carpal tunnel syndrome	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Hypoaesthesia	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Disturbance in attention	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Dysgeusia	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Syncope	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Burning sensation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Migraine	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Multiple sclerosis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Sensory disturbance	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Ageusia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Aphasia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Aphonia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Arachnoid cyst	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Autonomic nervous system imbalance	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Balance disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Cluster headache	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Dysaesthesia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Hemiparesis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Hyperaesthesia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Hypotonia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Memory impairment	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Movement disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Neurological symptom	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Paralysis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Psychomotor hyperactivity	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Somnolence	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Tension headache	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Tremor	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Nervous system disorders Ulnar tunnel syndrome	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Myalgia	0.15% 7/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Arthralgia	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Back pain	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Arthritis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Limb discomfort	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Lupus-like syndrome	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Muscle spasms	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Osteitis	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Bone pain	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Myofascial pain syndrome	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Tendonitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Toe deformity	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Bone disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Bursitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Fibromyalgia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Fistula	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Flank pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Groin pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Joint swelling	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Muscle tightness	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Muscular weakness	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Neck pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Osteoporosis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Sensation of heaviness	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Synovial cyst	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Musculoskeletal and connective tissue disorders Tenosynovitis stenosans	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hospitalisation	0.17% 8/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Dental operation	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hip arthroplasty	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Antibiotic prophylaxis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hip surgery	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Surgery	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Meniscus operation	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Tonsillectomy	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Arthrodesis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Dental treatment	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Hysterectomy	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Inguinal hernia repair	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Knee operation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Nasal septal operation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Tendon operation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Tooth extraction	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Allergenic desensitisation procedure	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Anorectal operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Aortic valve replacement	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Appendicectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Arthroscopic surgery	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Cervical conisation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Cholecystectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Chondroplasty	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Coronary angioplasty	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Coronary arterial stent insertion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Dental implantation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Eye laser surgery	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Female genital operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Haemorrhoid operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Heart valve operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Intervertebral disc operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Intestinal operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Joint irrigation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Knee arthroplasty	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Large intestine operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Laryngeal operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Meniscus removal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Oophorectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Otorhinolaryngological surgery	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Radiotherapy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Salpingectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Sigmoidectomy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Sinus operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Skin operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Spinal operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Testicular operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Toe operation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Surgical and medical procedures Uterine dilation and curettage	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Hepatic enzyme increased	0.34% 16/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Weight decreased	0.23% 11/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Transaminases increased	0.19% 9/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Alanine aminotransferase increased	0.17% 8/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Weight increased	0.17% 8/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Gamma-glutamyltransferase increased	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Arthroscopy	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Aspartate aminotransferase increased	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Blood pressure increased	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations C-reactive protein increased	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Blood count abnormal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Blood creatine phosphokinase increased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Blood testosterone decreased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Blood urine present	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Borrelia burgdorferi serology positive	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Computerised tomogram thorax abnormal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Double stranded DNA antibody	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Endoscopic retrograde cholangiopancreatography	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Haematology test	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Haemoglobin decreased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Hysteroscopy	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Laboratory test abnormal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Lipase increased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Prostatic specific antigen increased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Prothrombin time shortened	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Investigations Red blood cell sedimentation rate increased	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Cough	0.36% 17/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Asthma	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Tonsillar inflammation	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Productive cough	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Sneezing	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Respiratory, thoracic and mediastinal disorders Snoring	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Visual disturbance	0.21% 10/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Iritis	0.15% 7/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Eye pain	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Dry eye	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Uveitis	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Conjunctivitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Eye inflammation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Eye pruritus	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Iridocyclitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Ocular hyperaemia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Blepharospasm	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Cataract	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Chalazion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Conjunctival hyperaemia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Diplopia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Glaucoma	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Myopia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Ocular discomfort	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Sicca syndrome	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Ulcerative keratitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Eye disorders Visual acuity reduced	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Depression	0.17% 8/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Depressed mood	0.15% 7/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Sleep disorder	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Insomnia	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Loss of libido	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Agitation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Anxiety	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Emotional distress	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Restlessness	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Somatisation disorder	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Binge eating	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Confusional state	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Mental disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Nervousness	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Panic disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Psychosomatic disease	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Psychiatric disorders Somatoform disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Accident	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Tendon rupture	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Accident at work	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Clavicle fracture	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Fall	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Limb traumatic amputation	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Lower limb fracture	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Muscle injury	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Ankle fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Arthropod bite	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Contusion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Epicondylitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Excoriation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Fibula fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Forearm fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Hand fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Joint sprain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Open fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Post procedural complication	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Rib fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Skeletal injury	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Skin injury	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Skin laceration	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Tendon injury	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Traumatic brain injury	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Injury, poisoning and procedural complications Wrist fracture	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Arrhythmia	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Palpitations	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Pericarditis	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Tachycardia	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Cardiac failure	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Cardiovascular disorder	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Coronary artery disease	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Angina pectoris	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Aortic valve incompetence	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Arrhythmia supraventricular	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Cardiomegaly	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Mitral valve incompetence	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Cardiac disorders Pericardial effusion	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.45% 21/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Haematoma	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Hypertension	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Thrombosis	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Lymphoedema	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Hot flush	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Blood pressure fluctuation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Flushing	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Hypotension	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Vascular disorders Temporal arteritis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Erectile dysfunction	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Menorrhagia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Prostatitis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Breast cyst	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Endometrial hyperplasia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Hypomenorrhoea	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Menstruation irregular	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Metrorrhagia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Orchitis noninfective	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Reproductive system and breast disorders Prostatic disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Lymphadenopathy	0.11% 5/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Leukopenia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Anaemia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Anaemia neonatal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Haemolysis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Haemolysis neonatal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Lymphatic disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Neutropenia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Blood and lymphatic system disorders Platelet disorder	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seminoma	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign breast neoplasm	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Testis cancer	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Xanthoma	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Cholelithiasis	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Liver disorder	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Biliary colic	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Cholecystitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Gallbladder polyp	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Hepatitis	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Hepatomegaly	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Hepatobiliary disorders Hyperbilirubinaemia neonatal	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Immune system disorders Hypersensitivity	0.13% 6/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Immune system disorders Anaphylactic reaction	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Haematuria	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Leukocyturia	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Renal colic	0.04% 2/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Calculus ureteric	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Dysuria	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Renal and urinary disorders Nocturia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Ear and labyrinth disorders Tinnitus	0.06% 3/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Ear and labyrinth disorders Deafness unilateral	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Ear and labyrinth disorders Ear pain	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Ear and labyrinth disorders Middle ear inflammation	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Ear and labyrinth disorders Sudden hearing loss	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Metabolism and nutrition disorders Anorexia	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Metabolism and nutrition disorders Diabetes mellitus	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Metabolism and nutrition disorders Gout	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Metabolism and nutrition disorders Iron deficiency	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Metabolism and nutrition disorders Metabolic syndrome	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Metabolism and nutrition disorders Podagra	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Social circumstances Pregnancy of partner	0.09% 4/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Social circumstances Miscarriage of partner	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Congenital, familial and genetic disorders Dermoid cyst	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.
Endocrine disorders Hypothyroidism	0.02% 1/4681 • From signing of informed consent up to 24 months Drug related AEs and all serious adverse events (SAEs) were collected during the study period.

Additional Information

Global Medical Services

AbbVie (prior sponsor, Abbott)

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER