Axial Spondyloarthritis
Conditions
Brief summary
This study will evaluate how well adalimumab works in the short and long term in patients with axial spondyloarthritis who are not diagnosed as having either ankylosing spondylitis or psoriatic arthritis.
Detailed description
This is a Phase 3, placebo-controlled, double-blind randomized study with an open-label phase designed to evaluate the efficacy and safety of adalimumab 40 mg administered every other week in adult patients with active axial spondyloarthritis (SpA) who are not diagnosed with ankylosing spondylitis, psoriasis, or psoriatic arthritis and who have had an inadequate response or intolerance to one or more nonsteroidal anti-inflammatory drugs (NSAIDs) or had a contraindication to NSAIDs. Participants receive adalimumab or placebo for 12 weeks during the double-blind phase of the study. Following the double-blind phase, all remaining participants enter the open-label phase of the study in which they receive open-label adalimumab for up to 144 weeks. Efficacy endpoints include the Assessment of Spondyloarthritis International Society (ASAS) response criteria for patients with SpA. These response criteria were used to determine participants who were responders. ASAS response involves evaluations in the following 4 domains: participant's global assessment of disease activity, pain, function, and inflammation. The patient's global assessment of disease activity score is assessed using a 100 millimeter (mm) visual analog scale (VAS; 0 for no disease activity to 100 for severe disease activity). Pain is represented as a total back pain score and is assessed using a 100 mm VAS (0 for no pain to 100 for most severe pain). Function score is represented as the Bath Ankylosing Spondylitis (AS) Functional Index (BASFI) 100 mm VAS score (average of the ability to perform 10 activities, each scored as 0 for easy to 100 for impossible). Inflammation is determined using the morning stiffness overall level score (0 for none to 10 for very severe) and duration score (0 for 0 hours to 10 for ≥ 2 hours) of the Bath AS Disease Activity Index (BASDAI) (mean of these items #5 and #6 scores). In addition, the BASDAI is used as an efficacy endpoint. The BASDAI is used by the participant to assess his/her disease activity. Using VAS scales, the participant answers 6 questions pertaining to symptoms experienced over the past week. For 5 questions (levels of: fatigue/tiredness; AS neck, back, or hip pain; pain/swelling; discomfort at areas tender to touch or pressure; and morning stiffness), the response scale is 0 (none) to 10 (very severe). For 1 question (duration of morning stiffness), the response scale is 0 (0 hours) to 10 (≥ 2 or more hours).
Interventions
BIOLOGICALAdalimumab
40 mg every other week up to Week 12
BIOLOGICALPlacebo
Placebo every other week up to Week 12
BIOLOGICALOpen-label Adalimumab
40 mg every other week, Week 12 through Week 156
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients with inadequate response to \>/= 1 non-steroidal anti-inflammatory drugs (NSAIDs) * Chronic back pain with onset \< 45 years of age * Magnetic resonance imaging (MRI) indicating active sacroiliitis or positive human leukocyte antigen-B27 (HLA-B27) blood test in addition to meeting spondyloarthritis clinical criteria * Negative purified protein derivative (PPD) test and chest x-ray performed at Baseline visit must be negative * Ability to administer subcutaneous injections * General good health otherwise
Exclusion criteria
* Prior anti-tumor necrosis factor (TNF) therapy * Psoriasis or psoriatic arthritis * Fulfillment of modified New York criteria for ankylosing spondylitis * Recent infection requiring treatment * Significant medical events or conditions that may put patients at risk for participation * Females who are pregnant or breast-feeding or considering becoming pregnant during the study * History of cancer, except successfully treated skin cancer * Recent history of drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response | Baseline and Week 12 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score | Baseline and Week 12 | 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. |
| Number of Participants Achieving an ASAS5/6 Response | Baseline and Week 12 | 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). |
| Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) | Baseline and Week 12 | 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. |
| Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) | Baseline and Week 12 | 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. |
| Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints | Baseline and Week 12 | 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. |
| Change From Baseline in SPARCC MRI Score for the Spine | Baseline and Week 12 | 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. |
| Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response | Baseline and Week 12 | 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). |
| Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response | Baseline and Week 12 | 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. |
| Number of Participants Achieving ASAS Partial Remission | Week 12 | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving an ASAS20 Response During the Open-label Period | Baseline and Weeks 52, 104, and 156 | 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). |
| Number of Participants Achieving an ASAS40 Response During the Open-label Period | Baseline and Weeks 52, 104, and 156 | 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). |
| Number of Participants Achieving a BASDAI50 Response During the Open-label Period | Baseline and Weeks 52, 104, and 156 | 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. |
| Number of Participants Reporting Adverse Events | 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. |
| Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3 | 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Netherlands, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 94 |
| Double-blind 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. | 91 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Treatment Period | Adverse Event | 1 | 1 |
| Double-blind Treatment Period | Lack of Efficacy | 0 | 1 |
| Double-blind Treatment Period | MRI Not Diagnostic | 1 | 1 |
| Double-blind Treatment Period | Pregnancy | 0 | 1 |
| Open-label Treatment Period | Adverse Event | 4 | 8 |
| Open-label Treatment Period | Exclusion Criteria | 1 | 0 |
| Open-label Treatment Period | Lack of Efficacy | 6 | 9 |
| Open-label Treatment Period | Pregnancy | 1 | 1 |
| Open-label Treatment Period | Site Closure | 3 | 4 |
| Open-label Treatment Period | Withdrawal by Subject | 14 | 7 |
Baseline characteristics
| Characteristic | Placebo | Double-blind Adalimumab | Total |
|---|---|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 10.39 | 37.6 years STANDARD_DEVIATION 11.29 | 38.0 years STANDARD_DEVIATION 10.82 |
| Sex: Female, Male Female | 54 Participants | 47 Participants | 101 Participants |
| Sex: Female, Male Male | 40 Participants | 44 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 97 | 42 / 95 | 152 / 190 |
| serious Total, serious adverse events | 1 / 97 | 3 / 95 | 33 / 190 |
Outcome results
Primary
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response
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).
Time frame: Baseline and Week 12
Population: Full analysis set. Participants with missing data at Week 12 were counted as non-responders (non-responder imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response | 14 participants |
| Double-blind Adalimumab | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response | 33 participants |
p-value: <0.001Chi-squared
Secondary
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | 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 |
| Double-blind Adalimumab | Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) | -0.3 units on a scale | Standard Deviation 0.49 |
p-value: 0.027ANCOVA
Secondary
Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) | -0.3 mg/L | Standard Deviation 6.39 |
| Double-blind Adalimumab | Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) | -4.7 mg/L | Standard Deviation 12.32 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score
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.
Time frame: Baseline and Week 12
Population: Full analysis set with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score | 2.0 units on a scale | Standard Deviation 7.04 |
| Double-blind Adalimumab | Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score | 5.5 units on a scale | Standard Deviation 8.98 |
p-value: 0.001ANCOVA
Secondary
Change From Baseline in SPARCC MRI Score for the Spine
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.
Time frame: Baseline and Week 12
Population: Full analysis set; participants with non-missing Baseline and non-missing post-baseline value were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | Change From Baseline in SPARCC MRI Score for the Spine | -0.2 units on a scale | Standard Deviation 3.35 |
| Double-blind Adalimumab | Change From Baseline in SPARCC MRI Score for the Spine | -1.8 units on a scale | Standard Deviation 4.51 |
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints
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.
Time frame: Baseline and Week 12
Population: Full analysis set; participants with non-missing Baseline and non-missing post-baseline value were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | 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 |
| Double-blind Adalimumab | Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints | -3.2 units on a scale | Standard Deviation 8.34 |
p-value: 0.003ANCOVA
Secondary
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response
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.
Time frame: Baseline and Week 12
Population: Full analysis set; Non-responder imputation performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response | 14 participants |
| Double-blind Adalimumab | Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response | 32 participants |
p-value: 0.001Chi-squared
Secondary
Number of Participants Achieving an ASAS5/6 Response
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).
Time frame: Baseline and Week 12
Population: Full analysis set; Non-responder imputation performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Achieving an ASAS5/6 Response | 6 participants |
| Double-blind Adalimumab | Number of Participants Achieving an ASAS5/6 Response | 28 participants |
p-value: <0.001Chi-squared
Secondary
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response
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).
Time frame: Baseline and Week 12
Population: Full analysis set; Non-responder imputation performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response | 29 participants |
| Double-blind Adalimumab | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response | 47 participants |
p-value: 0.004Chi-squared
Secondary
Number of Participants Achieving ASAS Partial Remission
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).
Time frame: Week 12
Population: Full analysis set; Non-responder imputation performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Achieving ASAS Partial Remission | 5 participants |
| Double-blind Adalimumab | Number of Participants Achieving ASAS Partial Remission | 15 participants |
p-value: 0.014Chi-squared
Other Pre-specified
Number of Participants Achieving a BASDAI50 Response During the Open-label Period
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.
Time frame: Baseline and Weeks 52, 104, and 156
Population: Full analysis set participants with available data at each time point (indicated by N)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Placebo | Number of Participants Achieving a BASDAI50 Response During the Open-label Period | Week 52 (N=78, 72) | 52 participants |
| Double-blind Placebo | Number of Participants Achieving a BASDAI50 Response During the Open-label Period | Week 104 (N=74, 64) | 50 participants |
| Double-blind Placebo | Number of Participants Achieving a BASDAI50 Response During the Open-label Period | Week 156 (N=64, 58) | 46 participants |
| Double-blind Adalimumab | Number of Participants Achieving a BASDAI50 Response During the Open-label Period | Week 52 (N=78, 72) | 42 participants |
| Double-blind Adalimumab | Number of Participants Achieving a BASDAI50 Response During the Open-label Period | Week 104 (N=74, 64) | 40 participants |
| Double-blind Adalimumab | Number of Participants Achieving a BASDAI50 Response During the Open-label Period | Week 156 (N=64, 58) | 39 participants |
Other Pre-specified
Number of Participants Achieving an ASAS20 Response During the Open-label Period
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).
Time frame: Baseline and Weeks 52, 104, and 156
Population: Full analysis set participants with available data at each time point (as indicated by N)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Placebo | Number of Participants Achieving an ASAS20 Response During the Open-label Period | Week 104 (N=74, 64) | 59 participants |
| Double-blind Placebo | Number of Participants Achieving an ASAS20 Response During the Open-label Period | Week 156 (N=64, 58) | 53 participants |
| Double-blind Placebo | Number of Participants Achieving an ASAS20 Response During the Open-label Period | Week 52 (N=78, 72) | 59 participants |
| Double-blind Adalimumab | Number of Participants Achieving an ASAS20 Response During the Open-label Period | Week 104 (N=74, 64) | 53 participants |
| Double-blind Adalimumab | Number of Participants Achieving an ASAS20 Response During the Open-label Period | Week 156 (N=64, 58) | 48 participants |
| Double-blind Adalimumab | Number of Participants Achieving an ASAS20 Response During the Open-label Period | Week 52 (N=78, 72) | 57 participants |
Other Pre-specified
Number of Participants Achieving an ASAS40 Response During the Open-label Period
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).
Time frame: Baseline and Weeks 52, 104, and 156
Population: Full analysis set participants with available data at each time point (indicated by N)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Placebo | Number of Participants Achieving an ASAS40 Response During the Open-label Period | Week 52 (N=78, 72) | 50 participants |
| Double-blind Placebo | Number of Participants Achieving an ASAS40 Response During the Open-label Period | Week 104 (N=74, 64) | 51 participants |
| Double-blind Placebo | Number of Participants Achieving an ASAS40 Response During the Open-label Period | Week 156 (N=64, 58) | 44 participants |
| Double-blind Adalimumab | Number of Participants Achieving an ASAS40 Response During the Open-label Period | Week 52 (N=78, 72) | 42 participants |
| Double-blind Adalimumab | Number of Participants Achieving an ASAS40 Response During the Open-label Period | Week 156 (N=64, 58) | 37 participants |
| Double-blind Adalimumab | Number of Participants Achieving an ASAS40 Response During the Open-label Period | Week 104 (N=74, 64) | 38 participants |
Other Pre-specified
Number of Participants Reporting Adverse Events
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Reporting Adverse Events | 57 participants |
| Double-blind Adalimumab | Number of Participants Reporting Adverse Events | 55 participants |
Other Pre-specified
Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3 | 6 participants |
| Double-blind Adalimumab | Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3 | 4 participants |