Back to resultsContinuing Versus Withdrawing Adalimumab in Maintaining Remission in Non-Radiographic Axial Spondyloarthritis
Primary Purpose
Axial Spondyloarthritis
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
adalimumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Axial Spondyloarthritis focused on measuring Spondylitis, Spondylarthropathy, Ankylosing Spondyloarthritis, Spondyloarthritis, Spinal Diseases, Musculoskeletal Diseases, Arthritis, Joint Diseases, Adalimumab, Antirheumatic Agents, Anti-Inflammatory Agents
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Double-Blind Adalimumab
Open-label (OL) Adalimumab
Placebo
Arm Description
40 mg every other week (eow), Weeks 28-68. Blinded adalimumab was discontinued in participants who met the criteria for flare.
40 mg every other week (eow), Weeks 0-28. If participants flared during the double-blind period, they had an opportunity to receive at least 12 weeks of open-label adalimumab 40 mg eow.
Placebo every other week (eow), Weeks 28-68. Placebo was discontinued in participants who met the criteria for flare.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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).
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).
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).
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).
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.
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.
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.
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.
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.
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).
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).
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).
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).
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.
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 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 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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01808118
Brief Title
Continuing Versus Withdrawing Adalimumab in Maintaining Remission in Non-Radiographic Axial Spondyloarthritis
Official Title
A Multicenter, Randomized, Double-Blind, Study Comparing the Efficacy and Safety of Continuing Versus Withdrawing Adalimumab Therapy in Maintaining Remission in Subjects With Non-Radiographic Axial Spondyloarthritis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
April 16, 2013 (Actual)
Primary Completion Date
February 21, 2017 (Actual)
Study Completion Date
April 14, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Axial Spondyloarthritis
Keywords
Spondylitis, Spondylarthropathy, Ankylosing Spondyloarthritis, Spondyloarthritis, Spinal Diseases, Musculoskeletal Diseases, Arthritis, Joint Diseases, Adalimumab, Antirheumatic Agents, Anti-Inflammatory Agents
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
673 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Double-Blind Adalimumab
Arm Type
Experimental
Arm Description
40 mg every other week (eow), Weeks 28-68. Blinded adalimumab was discontinued in participants who met the criteria for flare.
Arm Title
Open-label (OL) Adalimumab
Arm Type
Experimental
Arm Description
40 mg every other week (eow), Weeks 0-28. If participants flared during the double-blind period, they had an opportunity to receive at least 12 weeks of open-label adalimumab 40 mg eow.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo every other week (eow), Weeks 28-68. Placebo was discontinued in participants who met the criteria for flare.
Intervention Type
Biological
Intervention Name(s)
adalimumab
Other Intervention Name(s)
Humira, ABT-D2E7
Intervention Description
40 mg every other week
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
every other week
Primary Outcome Measure Information:
Title
Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68
Description
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
Secondary Outcome Measure Information:
Title
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy
Description
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
Title
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68
Description
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
Title
Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68
Description
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
Title
Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68
Description
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
Title
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68
Description
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
Title
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68
Description
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
Title
Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68
Description
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
Title
Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68
Description
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
Title
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68
Description
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
Title
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68
Description
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
Title
Time to Flare at Week 68
Description
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
Title
Time to Partial Flare at Week 68
Description
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
Title
Number of Participants Reaching Flare Definition by Week 68
Description
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
Title
Number of Participants Reaching Partial Flare Definition by Week 68
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29961640
Citation
Landewe R, Sieper J, Mease P, Inman RD, Lambert RG, Deodhar A, Marzo-Ortega H, Magrey M, Kiltz U, Wang X, Li M, Zhong S, Mostafa NM, Lertratanakul A, Pangan AL, Anderson JK. Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study. Lancet. 2018 Jul 14;392(10142):134-144. doi: 10.1016/S0140-6736(18)31362-X. Epub 2018 Jun 29.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
Humira Prescribing Information
Learn more about this trial
Continuing Versus Withdrawing Adalimumab in Maintaining Remission in Non-Radiographic Axial Spondyloarthritis
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