A Study Treating Participants With Early Axial Spondyloarthritis (axSpA) Taking an Intense Treatment Approach Versus Routine Treatment

Study Overview
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Brief Summary
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A study comparing a treat-to-target (T2T) intense treatment approach with routine treatment (Standard of Care [SOC]) in reducing disease activity in participants with axial spondyloarthritis (axSpA).

Official Title
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STRIKE - Treating Patients With Early Axial Spondyloarthritis to Target - a 1 Year Randomized Controlled Study Taking an Intense Treatment Approach Versus Routine Treatment

Conditions
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Axial Spondyloarthritis

Intervention / Treatment
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* Biological: Adalimumab
* Other: Non-steroidal Anti-inflammatory Drugs (NSAIDs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent before start of study-related assessments or procedures Diagnosis of axSpA (either ankylosing spondylitis or non-radiographic axSpA) and fulfilling the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axSpA Participants aged ≥ 18 years Disease duration < 5 years Participants must have a Baseline disease activity as defined by an ASDAS ≥ 2.1 or a Bath AS Disease Activity Index (BASDAI) ≥ 4 NSAID-naive or not treated with the maximal recommended NSAID dose during the last 2 weeks prior to the Baseline visit Participants must never have failed a NSAID taken at maximal recommended dose for 2 weeks or more. Exclusion Criteria: Contraindications for NSAIDs or tumor necrosis factor (TNF) blocker according to local labeling If entering the study on concomitant NSAIDs, participants taking the maximal recommended dose during the last 2 weeks prior to the Baseline Visit or have failed or developed intolerance to a NSAID taken at maximal recommended dose for 2 weeks or more at any time Prior exposure to any anti-TNF therapy; any biologic therapy with a potential therapeutic impact on SpA, or participant has been treated with any investigational drug of chemical or biologic nature within a minimum of 30 days or five half-lives (whichever is longer) of the drug prior to the Baseline visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treat-to-Target (T2T)<br>Participants initially received treatment with any non-steroidal anti-inflammatory drug (NSAID) at full anti-inflammatory dose for 4 weeks. After 4 weeks, if the Ankylosing Spondylitis Disease Activity Score (ASDAS) was ≥ 2.1 or treatment with NSAID 1 was not tolerated, treatment was changed to a second NSAID at full anti-inflammatory dose for 4 weeks. If ASDAS was ≥ 2.1 after 4 weeks of NSAID 2 or treatment with the chosen NSAID was not tolerated, , participants were switched to receive a combination of NSAID and adalimumab 40 mg every other week for up to 48 weeks. | Biological: Adalimumab<br>* Administered every other week by subcutaneous injection for up to 48 weeks, depending on participants' disease activity.<br>* Other names: ABT-D2E7;|
| Active Comparator: Standard of Care (SOC)<br>Participants received treatment as prescribed by their physician according to the local standard of care. | Other: Non-steroidal Anti-inflammatory Drugs (NSAIDs)<br>* ASAS recommended NSAID doses to treat axial spondyloarthritis.<br>* Other names: Routine practice;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Ankylosing Spondylitis Disease Activity Score (ASDAS) of Inactive Disease at Week 32 | ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with ASDAS inactive disease (defined as ASDAS < 1.3) calculated using CRP is reported. | Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire | The EQ-5D-3L is a health state utility instrument that evaluates preference for health status (utility). The 5 items in the EQ-5D-3L comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on 3 levels of severity (1: indicating no problem, 2: indicating some/moderate problems, 3: indicating extreme problems). A single preference-weighted health utility index score was calculated by applying country-specific weights, with scores ranging from approximately 0 (death) to 1 (full health). | Baseline, week 32, and week 52 | 
| Change From Baseline in Work Productivity and Activity Impairment - Axial Spondyloarthritis (WPAI-axSpA): Presenteeism | The Work Productivity and Activity Impairment (WPAI) axSpA is an axSpA specific questionnaire consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement. | Baseline, week 32, and week 52 | 
| Change From Baseline in Work Productivity and Activity Impairment - Axial Spondyloarthritis (WPAI-axSpA): Absenteeism | The Work Productivity and Activity Impairment (WPAI) axSpA is an axSpA specific questionnaire consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement. | Baseline, week 32, and week 52 | 
| Change From Baseline in Work Productivity and Activity Impairment - Axial Spondyloarthritis (WPAI-axSpA): Total Work Productivity Impairment | The Work Productivity and Activity Impairment (WPAI) axSpA is an axSpA specific questionnaire consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement. | Baseline, week 32, and week 52 | 
| Change From Baseline in Work Productivity and Activity Impairment - Axial Spondyloarthritis (WPAI-axSpA): Total Activity Impairment | The Work Productivity and Activity Impairment (WPAI) axSpA is an axSpA specific questionnaire consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement. | Baseline, week 32, and week 52 | 
| Change From Baseline in Assessment of Spondyloarthritis International Society (ASAS) Health Index (HI) | The ASAS HI measures functioning and health across 17 aspects of health in patients with AS, including pain, emotional functions, sleep, sexual function, mobility, self care, and community life. The ASAS HI consists of 17 questions, each answered by the participant as agree (1) or disagree (0). The responses to the 17 dichotomous items are summed up to give a total score ranging from 0 to 17, with a lower score indicating a better and a higher score indicating an inferior health status. | Baseline, week 32, and week 52 | 
| Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index | The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 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 where lower scores indicate less disease activity. | Baseline, week 32, and week 52 | 
| Percentage of Participants Achieving a BASDAI 50 Response | The BASDAI 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. A BASDAI 50 response is defined as improvement of 50% or more from baseline in BASDAI score. | Baseline, week 32, and week 52 | 
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) | The Bath Ankylosing Spondylitis Functional Index (BASFI) is a validated index to determine the degree of functional limitation in patients with AS. BASFI consists of 10 questions assessing participants' ability to perform activities, on a numeric rating scale (NRS) ranging from 0 (easy to perform an activity) to 10 (impossible to perform an activity). The overall score is the mean of the 10 items and ranges from 0 (best) to 10 (worst). | Baseline, week 32, and week 52 | 
| Change From Baseline in ASDAS(CRP) | ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. Change from baseline in ASDAS calculated using CRP is reported. | Baseline, week 32, and week 52 | 
| Percentage of Participants Achieving ASDAS(CRP) Major Improvement | ASDAS Major Improvement is defined as a change from baseline ≤ -2.0. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with major improvement in ASDAS calculated using CRP is reported. | Baseline, week 32, and week 52 | 
| Percentage of Participants Achieving ASDAS(CRP) Clinically Important Improvement | ASDAS clinically important improvement is defined as a change from baseline ≤ -1.1. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with clinically important improvement in ASDAS calculated using CRP is reported. | Baseline, week 32, and week 52 | 
| Percentage of Participants With ASDAS Inactive Disease at Week 52 | ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with ASDAS inactive disease (defined as ASDAS < 1.3) calculated using CRP is reported. | Week 52 | 
| Percentage of Participants With ASDAS Low Disease Activity | ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with ASDAS low disease activity (defined as ASDAS < 2.1) calculated using CRP is reported. | Week 32 and week 52 | 
| Percentage of Participants With ASDAS Moderate Disease Activity | ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with ASDAS moderate disease activity (defined as an ASDAS ≥ 1.3 to < 2.1) calculated using CRP is reported. | Week 32 and week 52 | 
| Percentage of Participants With ASDAS High Disease Activity | ASDAS high disease activity is defined as an ASDAS ≥ 2.1 to < 3.5. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with high disease activity (defined as an ASDAS ≥ 2.1 to < 3.5) calculated using CRP is reported. | Week 32 and week 52 | 
| Percentage of Participants With ASDAS Very High Disease Activity | ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for inactive disease; ≥ 1.3 to < 2.1 for moderate disease activity; ≥ 2.1 to ≤ 3.5 for high disease activity and > 3.5 for very high disease activity. The percentage of participants with very high disease activity (defined as an ASDAS > 3.5) calculated using CRP is reported | Week 32 and week 52 | 
| Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response | ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 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). | Baseline, week 32, and week 52 | 
| Percentage of Participants Achieving an ASAS 40 Response | 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). | Baseline, week 32, and week 52 | 
| Percentage of Participants Achieving ASAS Partial Remission | 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). | Week 32 and week 52 | 
| Change From Baseline in Active Inflammation of the Sacroiliac Joints and Spine | Active inflammation of the sacroiliac (SI) joints as well as the cervical, thoracic and lumbar regions of the spine was assessed using magnetic resonance imaging (MRI). Images were scored by a central reader according to the Berlin MRI Score on a grading scale from 0 to 3, where Grade 0 indicates no active inflammation and Grade 3 indicates > 66% inflammation of the sacroiliac joints or > 50% active inflammation in the spine. | Baseline and week 52 | 
| Change From Baseline in Physician's Global Assessment of Disease Activity | The Physician's Global Assessment of Disease Activity was assessed using an NRS from 0 (no disease activity) to 10 (severe disease activity). | Baseline, week 32, and week 52 | 
| Change From Baseline in Patient's Global Assessment of Disease Activity | The Patient's Global Assessment of Disease Activity was assessed using an NRS from 0 (no disease activity) to 10 (very severe disease activity). | Baseline, week 32, and week 52 | 
| Change From Baseline in Patient's Global Assessment of Pain | The Patient's Global Assessment of Pain was assessed on a NRS from 0 (no pain) to 10 (pain as bad as it could be). | Baseline, week 32, and week 52 | 
| Change From Baseline in Swollen Joint Count | An assessment of 66 joints was performed by physical examination of each joint. The swollen joint count is the number of joints assessed as swollen (0 to 66). | Baseline, week 32, and week 52 | 
| Change From Baseline in Tender Joint Count | An assessment of 68 joints was performed by physical examination of each joint. The tender joint count is the number of joints assessed as tender (0 to 68). | Baseline, week 32, and week 52 | 
| Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) | The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at 13 entheses (sites where tendons or ligaments insert into the bone). All sites were scored as 0 (absent) or 1 (present). The MASES is the sum of all site scores (from 0 to 13). | Baseline, week 32, and week 52 | 
| Change From Baseline in Dactylitis Count | Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as 0 for no dactylitis or 1 for dactylitis present. The dactylitis count, ranging from 0 to 20, is the total number of digits on the hands and feet with dactylitis present. | Baseline, week 32, and week 52 | 
| Change From Baseline in the Erythrocyte Sedimentation Rate (ESR) | Erythrocyte sedimentation rate measures the rate of fall (sedimentation) of erythrocytes (red blood cells) in a sample of blood that has been placed into a tall, thin, vertical tube as an indirect measure of the degree of inflammation present in the body. | Baseline, week 32, and week 52 | 
| Change From Baseline in C-reactive Protein (CRP) | CRP is an acute phase reactant is a blood test marker for inflammation in the body. CRP levels rise in response to inflammation. | Baseline, week 32, and week 52 | 
| Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin) | The linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin) is a composite score based on 5 direct measurements of spinal mobility: lateral lumbar flexion, tragus-to-wall distance, lumbar flexion, intermalleolar distance, and cervical rotation angle. The total score ranges from 0 to 10, where higher scores indicate more limited mobility. | Baseline, week 32, and week 52 | 
| Number of Participants With New Onset Anterior Uveitis | Anterior uveitis is an inflammation of the middle layer of the eye. which includes the iris (colored part of the eye) and the adjacent tissue, known as the ciliary body. | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Axial Spondyloarthritis, Humira