Axial Spondyloarthritis
Conditions
Keywords
Spondylitis, Spondylarthropathy, Ankylosing Spondyloarthritis, Spondyloarthritis, Spinal Diseases, Musculoskeletal Diseases, Arthritis, Joint Diseases, Adalimumab, Antirheumatic Agents, Anti-Inflammatory Agents
Brief summary
The objective of this multicenter, randomized, double-blind study was to evaluate the efficacy and safety of continuing versus withdrawing therapy with adalimumab 40 mg given every other week SC in maintaining remission in subjects with moderate to severe non-radiographic axial spondyloarthritis.
Detailed description
The study duration included a 42-day Screening Period, a 28-week open-label 40 mg adalimumab every other week (eow) treatment period (Period 1), a 40-week double-blind placebo controlled eow treatment period (Period 2) with an opportunity to receive at least 12 weeks of rescue therapy with open-label adalimumab (participants that flared at Weeks 60, 64 or 68 were allowed 12 weeks of rescue therapy and final visits were at Weeks 72, 76 or 80 respectively), plus a 70-day follow-up phone call. Participants in sustained Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were randomized at Week 28 at a 1:1 ratio to receive either blinded adalimumab 40 mg eow or matching placebo. The length of exposure to adalimumab depended on remission or flare status and ranged from 20 (first time Ankylosing Spondylitis Disease Activity Score \[ASDAS\] remission was calculated) to 80 weeks of treatment.
Interventions
BIOLOGICALadalimumab
40 mg every other week
BIOLOGICALPlacebo
every other week
Sponsors
AbbVie
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 99 Years
Healthy volunteers
No
Inclusion criteria
* Adult participants with inadequate response to ≥2 nonsteroidal anti-inflammatory drugs (NSAIDs) * Participants with non-radiographic axial spondyloarthritis fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axial SpA classification criteria, but not fulfilling the radiologic criterion of the modified New York criteria for ankylosing spondylitis * Participants must have baseline disease activity as defined by having an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.100, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and Patient's Assessment of Total Back Pain score ≥ 4 based on a Numeric Rating Scale (NRS) at both the screening and baseline visits * Participants with evidence of active inflammation in the sacroiliac (SI) joints or spine on MRI, or elevated high sensitivity C-reactive protein (hs-CRP) at screening * Negative tuberculosis (TB) screening assessment * Ability to administer subcutaneous injections or have a qualified person available to administer injections * If female, either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or of childbearing potential and practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug. * Participant judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray, and a 12-lead electrocardiogram performed at screening
Exclusion criteria
* Prior anti-Tumor Necrosis Factor (TNF) therapy; biologic therapy with a potential therapeutic impact on SpA or treated with an investigational drug of chemical or biologic nature within 30 days or 5 half-lives prior to the baseline visit. * Fulfillment of the radiologic criterion of the modified New York criteria for Ankylosing Spondylitis at or prior to the screening visit * Recent infection requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the baseline visit or oral anti-infectives within 14 days prior to the baseline visit * Significant medical events or conditions that may put participants at risk for participation * Female participants who are pregnant or breast-feeding or considering becoming pregnant during the study * Known hypersensitivity to adalimumab or its excipients as stated in the label
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68 | From Week 28 through 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy | Baseline and Rescue Therapy Week 12 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Major Improvement is defined as a change from baseline ≤ -2.000. |
| Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy | Baseline and Rescue Therapy Week 12 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Clinically Important Improvement is defined as a change from baseline ≤ -1.100. |
| Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy | Baseline and Rescue Therapy Week 12 | ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 1 unit (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit) in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy | Baseline and Rescue Therapy Week 12 | ASAS40 response was defined as improvement of ≥ 40% relative to baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy | Baseline and Rescue Therapy Week 12 | An Assessment of Spondyloarthritis International Society (ASAS) 5/6 response is a 20% improvement in 5 out of the following 6 domains: * Patient's Global Assessment of disease activity, on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which assesses participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation: the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none) to 10 (very severe/2 hrs or more duration); * Spinal mobility: the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility); * High-sensitivity C-reactive protein level (lower levels = less inflammation). |
| Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy | Rescue Therapy Week 12 | Assessment in SpondyloArthritis International Society (ASAS) partial remission is defined as an absolute score of \< 2 units on a 0 to 10 scale for each of the four following domains: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 at 12 Weeks After Initiation of Rescue Therapy | Baseline and Rescue Therapy 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 point numeric rating scale \[NRS\]) 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. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from baseline in BASDAI score. |
| Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy | Baseline and Rescue Therapy 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 (very severe, high-dependency disability). Negative mean changes from baseline in the overall score indicate improvement. |
| Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68 | Weeks 28 and 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Inactive Disease is defined as a score of \<1.300. |
| Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Major Improvement is defined as a change from baseline ≤ -2.000. |
| Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy | Rescue Therapy Week 12 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Inactive Disease is defined as a score of \<1.300. |
| Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 1 unit (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit) in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | ASAS40 response was defined as improvement of ≥ 40% relative to baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 ASAS 5/6 Response at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | An Assessment of Spondyloarthritis International Society (ASAS) 5/6 response is a 20% improvement in 5 out of the following 6 domains: * Patient's Global Assessment of disease activity, on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which assesses participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation: the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none) to 10 (very severe/2 hrs or more duration); * Spinal mobility: the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility); * High-sensitivity C-reactive protein level (lower levels = less inflammation). |
| Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | Assessment in SpondyloArthritis International Society (ASAS) partial remission is defined as an absolute score of \< 2 units on a 0 to 10 scale for each of the four following domains: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale \[NRS\]) 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. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from baseline in BASDAI score. |
| Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | 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 (very severe, high-dependency disability). Negative mean changes from baseline in the overall score indicate improvement. |
| Time to Flare at Week 68 | From Week 28 through 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100. |
| Time to Partial Flare at Week 68 | From Week 28 through 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A partial flare was defined as having any 2 consecutive study visits with ASDAS ≥ 1.300 but \<2.100. |
| Number of Participants Reaching Flare Definition by Week 68 | From Week 28 through 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100. |
| Number of Participants Reaching Partial Flare Definition by Week 68 | From Week 28 through 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A partial flare was defined as having any 2 consecutive study visits with ASDAS ≥ 1.300 but \<2.100. |
| Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68 | Baseline, Weeks 28 and 68 | The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Clinically Important Improvement is defined as a change from baseline ≤ -1.100. |
Participant flow
Pre-assignment details
This study included a 42-day screening period.The Full Analysis Set (FAS) included all participants who enrolled in the open-label period (Period 1) and received at least 1 dose of adalimumab. The All Randomized Set included all Period 2 participants who were randomized to receive either placebo or 40 mg adalimumab every other week.
Participants by arm
| Arm | Count |
|---|---|
| Open-label (OL) Adalimumab (Period 1) 40 mg every other week (eow), Weeks 0-28. | 673 |
| Total | 673 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 | Adverse Event | 15 | 0 | 0 |
| Period 1 | Did not meet criteria for remission | 303 | 0 | 0 |
| Period 1 | Did not meet inclusion criteria | 3 | 0 | 0 |
| Period 1 | Enrolled in error | 7 | 0 | 0 |
| Period 1 | Investigator decision: site closure | 2 | 0 | 0 |
| Period 1 | Lack of Efficacy | 1 | 0 | 0 |
| Period 1 | Lost to Follow-up | 9 | 0 | 0 |
| Period 1 | Non-compliance per sponsor | 1 | 0 | 0 |
| Period 1 | Non-conformance with inclusion criteria | 3 | 0 | 0 |
| Period 1 | Withdrew consent | 24 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 4 | 0 |
| Period 2 | Investigator no longer conducting trials | 0 | 1 | 0 |
| Period 2 | Lost to Follow-up | 0 | 0 | 2 |
| Period 2 | Switched to other therapy | 0 | 1 | 0 |
| Period 2 | Withdrew consent | 0 | 7 | 6 |
Baseline characteristics
| Characteristic | Open-label (OL) Adalimumab (Period 1) |
|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 11.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 651 Participants |
| Sex: Female, Male Female | 343 Participants |
| Sex: Female, Male Male | 330 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 673 | 0 / 153 | 0 / 152 | 0 / 673 |
| other Total, other adverse events | 221 / 673 | 51 / 153 | 57 / 152 | 275 / 673 |
| serious Total, serious adverse events | 19 / 673 | 10 / 153 | 1 / 152 | 28 / 673 |
Outcome results
Primary
Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
Time frame: From Week 28 through 68
Population: Modified Intent-to-treat population: all participants who were randomized into double-blind Period 2 and received at least 1 dose of double-blind study medication; participants with missing data were inputed as nonresponders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68 | 72 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68 | 107 Participants |
p-value: <0.001Chi-squared
Secondary
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy
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 (very severe, high-dependency disability). Negative mean changes from baseline in the overall score indicate improvement.
Time frame: Baseline and Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Period 2) | Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy | -0.3 units on a scale | Standard Deviation 0.55 |
| Double-blind Adalimumab (Period 2) | Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy | -0.4 units on a scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68
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 (very severe, high-dependency disability). Negative mean changes from baseline in the overall score indicate improvement.
Time frame: Baseline, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Period 2) | Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68 | Week 28 | -0.8 units on a scale | Standard Deviation 0.58 |
| Double-blind Adalimumab (Period 2) | Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68 | Week 68 | -0.8 units on a scale | Standard Deviation 0.59 |
| Double-blind Adalimumab (Period 2) | Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68 | Week 68 | -0.8 units on a scale | Standard Deviation 0.63 |
Secondary
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy
The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale \[NRS\]) 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. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from baseline in BASDAI score.
Time frame: Baseline and Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy | 41 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy | 18 Participants |
Secondary
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68
The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale \[NRS\]) 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. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from baseline in BASDAI score.
Time frame: Baseline, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68 | Week 28 | 317 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68 | Week 68 | 72 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68 | Week 68 | 103 Participants |
Secondary
Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy
An Assessment of Spondyloarthritis International Society (ASAS) 5/6 response is a 20% improvement in 5 out of the following 6 domains: * Patient's Global Assessment of disease activity, on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which assesses participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation: the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none) to 10 (very severe/2 hrs or more duration); * Spinal mobility: the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility); * High-sensitivity C-reactive protein level (lower levels = less inflammation).
Time frame: Baseline and Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy | 25 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy | 9 Participants |
Secondary
Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68
An Assessment of Spondyloarthritis International Society (ASAS) 5/6 response is a 20% improvement in 5 out of the following 6 domains: * Patient's Global Assessment of disease activity, on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which assesses participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation: the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none) to 10 (very severe/2 hrs or more duration); * Spinal mobility: the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility); * High-sensitivity C-reactive protein level (lower levels = less inflammation).
Time frame: Baseline, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68 | Week 28 | 253 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68 | Week 68 | 49 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68 | Week 68 | 87 Participants |
Secondary
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy
ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 1 unit (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit) in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy | 46 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy | 19 Participants |
Secondary
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68
ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 1 unit (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit) in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68 | Week 28 | 315 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68 | Week 68 | 72 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68 | Week 68 | 107 Participants |
Secondary
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy
ASAS40 response was defined as improvement of ≥ 40% relative to baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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 Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy | 35 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy | 16 Participants |
Secondary
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68
ASAS40 response was defined as improvement of ≥ 40% relative to baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration in the potential remaining domain: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68 | Week 28 | 302 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68 | Week 68 | 70 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68 | Week 68 | 100 Participants |
Secondary
Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy
Assessment in SpondyloArthritis International Society (ASAS) partial remission is defined as an absolute score of \< 2 units on a 0 to 10 scale for each of the four following domains: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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: Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy | 26 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy | 15 Participants |
Secondary
Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68
Assessment in SpondyloArthritis International Society (ASAS) partial remission is defined as an absolute score of \< 2 units on a 0 to 10 scale for each of the four following domains: * Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68 | Week 28 | 224 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68 | Week 68 | 41 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68 | Week 68 | 64 Participants |
Secondary
Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Clinically Important Improvement is defined as a change from baseline ≤ -1.100.
Time frame: Baseline and Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy | 37 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy | 17 Participants |
Secondary
Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Clinically Important Improvement is defined as a change from baseline ≤ -1.100.
Time frame: Baseline, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68 | Week 28 | 316 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68 | Week 68 | 69 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68 | Week 68 | 102 Participants |
Secondary
Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Major Improvement is defined as a change from baseline ≤ -2.000.
Time frame: Baseline and Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy | 21 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy | 8 Participants |
Secondary
Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Major Improvement is defined as a change from baseline ≤ -2.000.
Time frame: Baseline, Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68 | Week 28 | 266 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68 | Week 68 | 49 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68 | Week 68 | 89 Participants |
Secondary
Number of Participants Reaching Flare Definition by Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
Time frame: From Week 28 through 68
Population: Modified Intent-to-treat population: all participants who were randomized into double-blind Period 2 and received at least 1 dose of double-blind study medication; participants with missing data were inputed as nonresponders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Reaching Flare Definition by Week 68 | 81 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Reaching Flare Definition by Week 68 | 45 Participants |
Secondary
Number of Participants Reaching Partial Flare Definition by Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A partial flare was defined as having any 2 consecutive study visits with ASDAS ≥ 1.300 but \<2.100.
Time frame: From Week 28 through 68
Population: Modified Intent-to-treat population: all participants who were randomized into double-blind Period 2 and received at least 1 dose of double-blind study medication; participants with missing data were inputed as nonresponders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants Reaching Partial Flare Definition by Week 68 | 98 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants Reaching Partial Flare Definition by Week 68 | 62 Participants |
Secondary
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Inactive Disease is defined as a score of \<1.300.
Time frame: Rescue Therapy Week 12
Population: Rescued Population: participants with available data who received open-label rescue treatment after the double-blind period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Period 2) | Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy | 37 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy | 20 Participants |
Secondary
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Inactive Disease is defined as a score of \<1.300.
Time frame: Weeks 28 and 68
Population: Period 1 (all enrolled participants who received at least 1 dose of adalimumab); Period 2 (mITT: all randomized participants who received at least 1 dose of double-blind study medication); participants with missing data were inputed as nonresponders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Period 2) | Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68 | Week 28 | 295 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68 | Week 68 | 51 Participants |
| Double-blind Adalimumab (Period 2) | Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68 | Week 68 | 87 Participants |
Secondary
Time to Flare at Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
Time frame: From Week 28 through 68
Population: Modified Intent-to-treat population: all participants who were randomized into double-blind Period 2 and received at least 1 dose of double-blind study medication; participants with missing data were treated as missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Period 2) | Time to Flare at Week 68 | NA weeks |
| Double-blind Adalimumab (Period 2) | Time to Flare at Week 68 | NA weeks |
Comparison: The statistical test was performed at a 2-sided significance level of 0.05. Time to flare analysis showed statistically significant lower risk of flare in the adalimumab group than in the placebo group.p-value: <0.001Log Rank
Secondary
Time to Partial Flare at Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A partial flare was defined as having any 2 consecutive study visits with ASDAS ≥ 1.300 but \<2.100.
Time frame: From Week 28 through 68
Population: Modified Intent-to-treat population: all participants who were randomized into double-blind Period 2 and received at least 1 dose of double-blind study medication; participants with missing data were treated as missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Period 2) | Time to Partial Flare at Week 68 | 41 weeks |
| Double-blind Adalimumab (Period 2) | Time to Partial Flare at Week 68 | 42 weeks |