Trial Outcomes & Findings for Study of Adalimumab in Patients With Axial Spondyloarthritis (NCT NCT00939003)

Last Updated: 2014-09-09

Results Overview

ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 20 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of \> 0 units on a scale from 0 to 100) in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); * Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

192 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2014-09-09

Participant Flow

A total of 192 participants were enrolled at 37 study sites in Australia, Belgium, Canada, the Czech Republic, France, Germany, the Netherlands, Spain, the United Kingdom, and the US. Due to Investigator non-compliance with protocol requirements, 1 study site was closed; the 7 participants enrolled at this site were excluded from efficacy analyses.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.	Adalimumab Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.
Double-blind Treatment Period STARTED	97	95
Double-blind Treatment Period COMPLETED	95	91
Double-blind Treatment Period NOT COMPLETED	2	4
Open-label Treatment Period STARTED	95	91
Open-label Treatment Period COMPLETED	66	62
Open-label Treatment Period NOT COMPLETED	29	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.	Adalimumab Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.
Double-blind Treatment Period Adverse Event	1	1
Double-blind Treatment Period Lack of Efficacy	0	1
Double-blind Treatment Period Pregnancy	0	1
Double-blind Treatment Period MRI Not Diagnostic	1	1
Open-label Treatment Period Adverse Event	4	8
Open-label Treatment Period Withdrawal by Subject	14	7
Open-label Treatment Period Lack of Efficacy	6	9
Open-label Treatment Period Pregnancy	1	1
Open-label Treatment Period Exclusion Criteria	1	0
Open-label Treatment Period Site Closure	3	4

Baseline Characteristics

Study of Adalimumab in Patients With Axial Spondyloarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=94 Participants Participants received placebo every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.	Double-blind Adalimumab n=91 Participants Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.	Total n=185 Participants Total of all reporting groups
Age, Continuous	38.4 years STANDARD_DEVIATION 10.39 • n=5 Participants	37.6 years STANDARD_DEVIATION 11.29 • n=7 Participants	38.0 years STANDARD_DEVIATION 10.82 • n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	47 Participants n=7 Participants	101 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	44 Participants n=7 Participants	84 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set. Participants with missing data at Week 12 were counted as non-responders (non-responder imputation).

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response	14 participants	33 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set; Non-responder imputation performed.

ASAS20 response was defined as improvement of ≥ 20% relative to Baseline and absolute improvement of ≥ 10 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a change for the worse of ≥ 20% and net worsening of ≥ 10 units) in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); * Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response	29 participants	47 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set; Non-responder imputation performed.

The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 cm VAS) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10 cm. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from Baseline in BASDAI score.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response	14 participants	32 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set with available data

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life. The SF-36 consists of 36 questions in 8 domains (limitations in physical functioning due to health problems; limitations in usual role because of physical health problems; bodily pain; general health perceptions; vitality; limitations in social functioning because of physical or emotional problems; limitations in usual role due to emotional problems; and general mental health). Two component scores can be summarized: physical and mental; domains 1-4 comprise the physical component summary of the SF-36. A transformed summary score is calculated ranging from 0 to 100 where higher scores indicate a higher level of functioning. A positive change from Baseline score indicates an improvement.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=93 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score	2.0 units on a scale Standard Deviation 7.04	5.5 units on a scale Standard Deviation 8.98

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set; Non-responder imputation performed.

ASAS partial remission is an absolute score of \< 20 units on a 0 to 100 scale for each of the four following domains: * Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); * Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving ASAS Partial Remission	5 participants	15 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set; Non-responder imputation performed.

ASAS5/6 response is a 20% improvement in five out of the following six domains: * Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); * Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none) to 10 (very severe/2 hours or more duration). * Spinal mobility, measured from the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility); * C-reactive protein level (lower levels indicate less inflammation).

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving an ASAS5/6 Response	6 participants	28 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set; participants with non-missing Baseline and at least one non-missing post-baseline values were included. Last observation carried forward was used.

Health Assessment Questionnaire modified for spondyloarthropathies (HAQ-S) is a self-reported measure to assess the physical function and health-related quality of life. The Disability Index (DI) of HAQ-S is calculated as the mean of the following 8 category scores (range: 0 \[without any difficulty\] to 3 \[unable to do\]): Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Five additional items in the functional status measure were included in the HAQ-S, including carrying heavy packages, sitting for long periods, able to work at a flat topped table, and (if the participant had a driver's license or a car) able to look in the rear view mirror and able to turn head to drive in reverse. The overall score ranges from 0 (no disability) to 3 (three very severe, high-dependency disability). Negative mean changes from Baseline in the overall score indicate improvement.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S)	-0.1 units on a scale Standard Deviation 0.42	-0.3 units on a scale Standard Deviation 0.49

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set; participants with non-missing Baseline and at least one non-missing post-baseline value were included. Last observation carried forward was used.

C-reactive protein (CRP) is considered an efficacy variable for the axial spondyloarthritis indication. It is a general marker of inflammation that is sensitive to acute changes in inflammatory response. Higher levels indicate more inflammation.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=73 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=70 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)	-0.3 mg/L Standard Deviation 6.39	-4.7 mg/L Standard Deviation 12.32

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set; participants with non-missing Baseline and non-missing post-baseline value were included.

Six consecutive sacroiliac (SI) joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema using SPARCC scoring. Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema; the maximum score is 8 per slice and maximum score for 6 SI joint slices is 48. Intensity of edema: A score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice. The maximum score is 2 per slice and 12 for 6 slices. A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant. The maximum score per slice is 2 and for 6 slices 12. The total maximum score for all SI joints across 6 slices is 72.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=84 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=84 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints	-0.6 units on a scale Standard Deviation 6.19	-3.2 units on a scale Standard Deviation 8.34

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set; participants with non-missing Baseline and non-missing post-baseline value were included.

Six discovertebral units (DVU) representing the 6 most abnormal DVUs, and 3 consecutive sagittal slices at each DVU representing the most abnormal slices for that DVU were selected for scoring. Each DVU was divided into 4 quadrants and scored for the presence (1) or absence (0) of edema. The maximum score is 12 per DVU. The maximum score is 72 for 6 DVUs. If edema was present in at least 1 quadrant of a DVU slice, it was scored for intensity and depth of the edema representing that slice: A score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. The maximum score for intensity per slice is 1, per DVU is 3 and for 6 DVUs is 18. A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the surface of the endplate in any quadrant. The maximum score per slice is 1, for a DVU is 3 and for 6 DVUs is 18. The total maximum SPARCC score for all 6 DVUs is 108.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=82 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=85 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Change From Baseline in SPARCC MRI Score for the Spine	-0.2 units on a scale Standard Deviation 3.35	-1.8 units on a scale Standard Deviation 4.51

OTHER_PRE_SPECIFIED outcome

Timeframe: Through Week 12

Population: All participants who received at least 1 dose of study drug. For the double-blind phase of the study, adverse events are reported through Week 12.

Adverse events were collected at designated study visits for all participants who received at least 1 dose of study drug. The number of participants experiencing any adverse event (serious and non-serious) is summarized.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=97 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=95 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Reporting Adverse Events	57 participants	55 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Through Week 12

Population: All participants who received at least 1 dose of study drug. Results for the double-blind phase phase of the study are reported through Week 12.

Blood was collected for analysis at designated study visits; hematology and chemistry results were provided by a central laboratory. The number of participants with an abnormal laboratory result (higher then upper normal limit or lower than lower normal limit) meeting Common Toxicity Criteria (CTC) of Grade 3 or higher is summarized.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=97 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=95 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3	6 participants	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 52, 104, and 156

Population: Full analysis set participants with available data at each time point (as indicated by N)

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving an ASAS20 Response During the Open-label Period Week 52 (N=78, 72)	59 participants	57 participants
Number of Participants Achieving an ASAS20 Response During the Open-label Period Week 104 (N=74, 64)	59 participants	53 participants
Number of Participants Achieving an ASAS20 Response During the Open-label Period Week 156 (N=64, 58)	53 participants	48 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 52, 104, and 156

Population: Full analysis set participants with available data at each time point (indicated by N)

ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 20 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of \> 0 units on a scale of 0 to 100) in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); * Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving an ASAS40 Response During the Open-label Period Week 52 (N=78, 72)	50 participants	42 participants
Number of Participants Achieving an ASAS40 Response During the Open-label Period Week 104 (N=74, 64)	51 participants	38 participants
Number of Participants Achieving an ASAS40 Response During the Open-label Period Week 156 (N=64, 58)	44 participants	37 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 52, 104, and 156

Population: Full analysis set participants with available data at each time point (indicated by N)

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=94 Participants Double-blind placebo every other week for 12 weeks	Double-blind Adalimumab n=91 Participants Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks
Number of Participants Achieving a BASDAI50 Response During the Open-label Period Week 52 (N=78, 72)	52 participants	42 participants
Number of Participants Achieving a BASDAI50 Response During the Open-label Period Week 104 (N=74, 64)	50 participants	40 participants
Number of Participants Achieving a BASDAI50 Response During the Open-label Period Week 156 (N=64, 58)	46 participants	39 participants

Adverse Events

Double-blind Placebo

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Double-blind Adalimumab

Serious events: 3 serious events

Other events: 42 other events

Deaths: 0 deaths

Any Adalimumab

Serious events: 33 serious events

Other events: 152 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	Double-blind Placebo n=97 participants at risk Participants received placebo every other week for 12 weeks during the double-blind period.	Double-blind Adalimumab n=95 participants at risk Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period.	Any Adalimumab n=190 participants at risk Participants who received any dose of adalimumab during the 12-week double-blind period or during the 144-week open-label period.
Musculoskeletal and connective tissue disorders PERIARTHRITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Cardiac disorders CARDIOPULMONARY FAILURE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Ear and labyrinth disorders VERTIGO	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Endocrine disorders GOITRE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Eye disorders MACULAR DEGENERATION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Eye disorders OSCILLOPSIA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders CONSTIPATION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders DIARRHOEA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders NAUSEA	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders STOMATITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders VOMITING	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders CHEST PAIN	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders CHILLS	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders NON-CARDIAC CHEST PAIN	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders PYREXIA	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Hepatobiliary disorders CHOLECYSTITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Hepatobiliary disorders HEPATITIS ACUTE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations BURSITIS INFECTIVE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations CELLULITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 2/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations DISSEMINATED TUBERCULOSIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations DIVERTICULITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations PILONIDAL CYST	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations POSTOPERATIVE WOUND INFECTION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations SINUSITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations TONSILLITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Injury, poisoning and procedural complications FALL	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Injury, poisoning and procedural complications INCISIONAL HERNIA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Injury, poisoning and procedural complications LACERATION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Injury, poisoning and procedural complications PROCEDURAL PAIN	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders LUPUS-LIKE SYNDROME	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders TENDON CALCIFICATION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Nervous system disorders DIZZINESS	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Nervous system disorders HEADACHE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 2/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Nervous system disorders MIGRAINE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Pregnancy, puerperium and perinatal conditions ABORTION SPONTANEOUS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Psychiatric disorders COMPLETED SUICIDE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Psychiatric disorders SUICIDE ATTEMPT	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Reproductive system and breast disorders BREAST DYSPLASIA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Reproductive system and breast disorders MENORRHAGIA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Reproductive system and breast disorders VAGINAL PROLAPSE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Respiratory, thoracic and mediastinal disorders COUGH	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Skin and subcutaneous tissue disorders RASH	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Surgical and medical procedures ABORTION INDUCED	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.53% 1/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.

Measure	Double-blind Placebo n=97 participants at risk Participants received placebo every other week for 12 weeks during the double-blind period.	Double-blind Adalimumab n=95 participants at risk Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period.	Any Adalimumab n=190 participants at risk Participants who received any dose of adalimumab during the 12-week double-blind period or during the 144-week open-label period.
Eye disorders CONJUNCTIVITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders CONSTIPATION	3.1% 3/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 2/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders DIARRHOEA	7.2% 7/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.2% 4/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	9.5% 18/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Gastrointestinal disorders NAUSEA	7.2% 7/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	7.4% 7/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	6.8% 13/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders ASTHENIA	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 3/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.7% 7/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders FATIGUE	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 3/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	7.4% 14/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders INJECTION SITE ERYTHEMA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 3/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders INJECTION SITE PAIN	3.1% 3/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 2/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders INJECTION SITE REACTION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.2% 4/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	5.8% 11/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
General disorders PYREXIA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.2% 8/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations BRONCHITIS	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	16.3% 31/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations CYSTITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.7% 7/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations GASTROENTERITIS	3.1% 3/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	5.8% 11/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations INFLUENZA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations NASOPHARYNGITIS	3.1% 3/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	11.6% 11/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	27.4% 52/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations ORAL HERPES	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations PHARYNGITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 3/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	7.9% 15/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations RHINITIS	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations SINUSITIS	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	9.5% 18/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations TONSILLITIS	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	4.1% 4/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 3/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	10.0% 19/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations URINARY TRACT INFECTION	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.7% 7/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations VAGINAL INFECTION	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Infections and infestations VULVOVAGINAL MYCOTIC INFECTION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.7% 7/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Injury, poisoning and procedural complications CONTUSION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.7% 7/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Injury, poisoning and procedural complications FALL	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Investigations ALANINE AMINOTRANSFERASE INCREASED	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Metabolism and nutrition disorders HYPERCHOLESTEROLAEMIA	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders ARTHRALGIA	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	5.8% 11/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders BACK PAIN	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	6.8% 13/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders BURSITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders MYALGIA	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.7% 7/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders SPONDYLITIS	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	19.5% 37/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders SPONDYLOARTHROPATHY	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.2% 8/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders SYNOVIAL CYST	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Musculoskeletal and connective tissue disorders TENDONITIS	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Nervous system disorders HEADACHE	3.1% 3/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	6.3% 6/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	10.0% 19/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Psychiatric disorders ANXIETY	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	5.8% 11/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Psychiatric disorders DEPRESSION	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.7% 7/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Psychiatric disorders INSOMNIA	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Respiratory, thoracic and mediastinal disorders COUGH	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.2% 8/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	0.00% 0/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Skin and subcutaneous tissue disorders PRURITUS	1.0% 1/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	1.1% 1/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Skin and subcutaneous tissue disorders RASH	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	2.1% 2/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	3.2% 6/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.
Vascular disorders HYPERTENSION	2.1% 2/97 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	0.00% 0/95 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.	4.7% 9/190 • Twelve weeks during the double blind period and up to Week 156 during the open-label period.