Back to resultsREduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)
Primary Purpose
Ankylosing Spondylitis, Axial Spondyloarthritis
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Adalimumab and its biosimilars
Biological: Etanercept and its biosimilars
Golimumab
Infliximab biosimilar
Sponsored by
About this trial
This is an interventional treatment trial for Ankylosing Spondylitis
Eligibility Criteria
Inclusion Criteria:
- Documented diagnosis of Ankylosing spondylitis (AS) and meet the modified New York classification criteria for AS.
- Subjects maintaining stable disease (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] < 4) with standard-dose subcutaneous tumor-necrosis factor inhibitor (TNFi) treatment during previous 6 months from screening.
- Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 at screening and 12 weeks prior to screening
- In subjects treated with methotrexate or sulfasalazine, the dose should be maintained (methotrexate≤ 25mg/day, sulfasalazine ≤ 3 g/day) during previous 4 weeks before screening.
- In subjects treated with systemic glucocorticoids, the dose should be less than 10mg/day of predinisolone or equivalent during at least 2 weeks from the screening
- Subjects with stable dose of concomitant NSAID (including Cox2 inhibitors) during the 2 weeks from the randomization
Exclusion Criteria:
- Exposure to more than 1 TNFi
- History of hypersensitivity reaction to any TNFis
- Subjects with concomitant fibromyalgia, as determined by the investigator
- Subjects who have received any TNFis with reduced dosage
- Presence of total spinal ankylosis ('Bamboo spine')
- Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study
- Subjects with a history of malignancies and lymphoproliferative disorder including lymphoma within 5 years (Basal cell carcinoma treated within previous 3 months and showing no evidence of recurrence, actinic keratosis, and treated cervical/colon carcinoma in situ were allowed.)
- Subjects with current or history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac or neurological disease, as determined by the investigator
Subjects with significant laboratory abnormalities included but not limited to:
- AST/ALT > 3.0 X ULN
- White blood cell (WBC) < 3000/μL and/or absolute neutrophil count (ANC) < 1500/μL
- Platelet count <100,000/μL and/or hemoglobin level <8.5 g/dL
- Serum creatinine ≥ 1.5 X ULN
- Subjected with any high-potency opioids (ex. methadone, hydromorphone, morphine, oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, meperidine)
- Subjects with current acute or chronic viral hepatitis B or C or with human immunodeficiency virus (HIV) infection
- Subjects planning to receive any live attenuated vaccinations after screening
- Subjects has history of chronic alcohol abuse or drug abuse within 6 months from screening
- Subjects concomitantly treated with systemic glucocorticoid (>10mg/day of prednisolone or equivalent doses)
- Subjects with any other condition that, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Open-label reduced-dose TNFi
Open-label full-dose TNFi
Arm Description
Participants in the experimental arm will receive one of the intervention below according to the TNFi agent used at baseline: Adalimumab 40mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48. Etanercept 50mg subcutaneous every 10 days (Q10D) from week 0 to week 48. Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 5 weeks (Q5W) from week 0 to week 48. Remsima SC 120mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48.
Participants in the comparator arm will receive one of the intervention below according to the TNFi agent used at baseline: Adalimumab 40mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48. Etanercept 50mg subcutaneous every week (QW) from week 0 to week 48. Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 4 weeks (Q4W) from week 0 to week 48. Remsima SC 120mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48.
Outcomes
Primary Outcome Measures
Percentage of Participants who did not experience a flare
Flare is defined as below:
A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥ 2.1) at 2 consecutive visits or an ASDAS greater than (> 3.5) at any visit.
If a participant had an ASDAS ≥ 2.1 and ≤ 3.5, the participant has an additional visit 4 weeks later and ASDAS is assessed by the investigator to confirm the flare.
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Secondary Outcome Measures
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 12.
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 24.
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 36.
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 48.
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 12.
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 24.
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 36.
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 48.
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 12.
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 24.
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 36.
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 48.
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 12.
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 24.
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 36.
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 48.
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 12.
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 24.
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 36.
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 48.
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 12.
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 24.
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 36.
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 48.
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 12.
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 24.
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 36.
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 48.
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at week 24.
The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at week 48.
The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Change from baseline in Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) at week 24.
The Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) is a disease-specific measure to assess the level of enthesitis in Ankylosing Spondylitis. It is based on clinical examination by assessor who determined by presence (score 1) or absence (score 0) of enthesitis at 13 different sites as below:
Both 1st costochondral
Both 7th costochondral
Both iliac crest
Both anterior superior iliac spine
Both posterior superior iliac spine
Both proximal Achilles tendon
5th lumbar spinous process
Change from baseline in Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) at week 48.
The Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) is a disease-specific measure to assess the level of enthesitis in Ankylosing Spondylitis. It is based on clinical examination by assessor who determined by presence (score 1) or absence (score 0) of enthesitis at 13 different sites as below:
Both 1st costochondral
Both 7th costochondral
Both iliac crest
Both anterior superior iliac spine
Both posterior superior iliac spine
Both proximal Achilles tendon
5th lumbar spinous process
Change from baseline in swollen/tender joint count (0-44) at week 24.
American College of Rheumatology (ACR), swollen joint count were an assessment of 44 joints. Joints are classified as either swollen or not swollen (tender or non-tender). An increase in swollen joints from baseline represented disease progression and/or joint worsening.
Change from baseline in swollen/tender joint count (0-44) at week 48.
American College of Rheumatology (ACR), swollen joint count were an assessment of 44 joints. Joints are classified as either swollen or not swollen (tender or non-tender). An increase in swollen joints from baseline represented disease progression and/or joint worsening.
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 12.
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 24.
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 36.
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 48.
Change from baseline in serum C-Reactive Protein (CRP) level at week 12.
Change from baseline in serum C-Reactive Protein (CRP) level at week 24.
Change from baseline in serum C-Reactive Protein (CRP) level at week 36.
Change from baseline in serum C-Reactive Protein (CRP) level at week 48.
Change from baseline in Assessment of SpondyloArthritis international Society (ASAS)-health index (ASAS-HI) at week 24.
The self-report questionnaire measures functioning and health across 17 aspects of health and 9 environmental factors (EF) in patients with spondyloarthritis. The ASAS HI contains items addressing categories of pain, emotional functions, sleep, sexual function, mobility, self care, and community life.
Change from baseline in Assessment of SpondyloArthritis international Society (ASAS)-health index (ASAS-HI) at week 48.
The self-report questionnaire measures functioning and health across 17 aspects of health and 9 environmental factors (EF) in patients with spondyloarthritis. The ASAS HI contains items addressing categories of pain, emotional functions, sleep, sexual function, mobility, self care, and community life.
Change from baseline in 5-level EQ-5D version (EQ-5D-5L) at week 24.
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.
Change from baseline in 5-level EQ-5D version (EQ-5D-5L) at week 48.
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.
The amount of NSAID intake between week 0 and 12
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
The amount of NSAID intake between week 12 and 24
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
The amount of NSAID intake between week 24 and 36
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
The amount of NSAID intake between week 36 and 48
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
Percentage of patients at Least One Adverse Event (AE) During the study period.
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Full Information
NCT ID
NCT05164198
First Posted
November 8, 2021
Last Updated
December 6, 2021
Sponsor
Hanyang University Seoul Hospital
Collaborators
Linical Korea
1. Study Identification
Unique Protocol Identification Number
NCT05164198
Brief Title
REduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)
Official Title
Multicenter, Prospective Clinical Trial for Optimizing TNF Inhibitor Dose Adjustment in Ankylosing Spondylitis Patients With Stable Disease Activity
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 15, 2022 (Anticipated)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hanyang University Seoul Hospital
Collaborators
Linical Korea
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
Yes
5. Study Description
Brief Summary
Participants maintaining stable disease activity of Ankylosing Spondylitis (AS) with standard-dose tumor necrosis factor inhibitor (TNFi) treatment will randomly split into two groups: maintaining standard-dose TNFi, versus reduced-dose TNFi. The proportion of participants not underwent flare between the two groups will be analyzed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ankylosing Spondylitis, Axial Spondyloarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Phase 4, randomized, parallel, non-inferiority, open-label, multi-center clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
448 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Open-label reduced-dose TNFi
Arm Type
Experimental
Arm Description
Participants in the experimental arm will receive one of the intervention below according to the TNFi agent used at baseline:
Adalimumab 40mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48.
Etanercept 50mg subcutaneous every 10 days (Q10D) from week 0 to week 48.
Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 5 weeks (Q5W) from week 0 to week 48.
Remsima SC 120mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48.
Arm Title
Open-label full-dose TNFi
Arm Type
Active Comparator
Arm Description
Participants in the comparator arm will receive one of the intervention below according to the TNFi agent used at baseline:
Adalimumab 40mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48.
Etanercept 50mg subcutaneous every week (QW) from week 0 to week 48.
Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 4 weeks (Q4W) from week 0 to week 48.
Remsima SC 120mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48.
Intervention Type
Biological
Intervention Name(s)
Adalimumab and its biosimilars
Other Intervention Name(s)
Humira, Adaloce
Intervention Description
Active substance: Adalimumab
Pharmaceutical form: Prefilled syringe
Concentration: 100mg/mL
Route of administration: Subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
Biological: Etanercept and its biosimilars
Other Intervention Name(s)
Enbrel, Eucept, Etalace
Intervention Description
Active substance: Etanercept
Pharmaceutical form: Prefilled syringe
Concentration: 50mg/mL
Route of administration: Subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
Golimumab
Other Intervention Name(s)
Simponi
Intervention Description
Active substance: Adalimumab
Pharmaceutical form: Prefilled syringe
Concentration: 100mg/mL
Route of administration: Subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
Infliximab biosimilar
Other Intervention Name(s)
Remsima
Intervention Description
Active substance: Infliximab
Pharmaceutical form: Prefilled syringe
Concentration: 120mg/mL
Route of administration: Subcutaneous injection
Primary Outcome Measure Information:
Title
Percentage of Participants who did not experience a flare
Description
Flare is defined as below:
A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥ 2.1) at 2 consecutive visits or an ASDAS greater than (> 3.5) at any visit.
If a participant had an ASDAS ≥ 2.1 and ≤ 3.5, the participant has an additional visit 4 weeks later and ASDAS is assessed by the investigator to confirm the flare.
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Time Frame
From week 0 to week 48
Secondary Outcome Measure Information:
Title
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 12.
Description
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Time Frame
Week 12
Title
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 24.
Description
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Time Frame
Week 24
Title
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 36.
Description
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Time Frame
Week 36
Title
Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 48.
Description
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.
Time Frame
Week 48
Title
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 12.
Description
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Time Frame
Week 12
Title
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 24.
Description
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Time Frame
Week 24
Title
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 36.
Description
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Time Frame
Week 36
Title
Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 48.
Description
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity.
Time Frame
Week 48
Title
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 12.
Description
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 12
Title
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 24.
Description
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 24
Title
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 36.
Description
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 36
Title
Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 48.
Description
The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 48
Title
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 12.
Description
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 12
Title
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 24.
Description
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 24
Title
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 36.
Description
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 36
Title
Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 48.
Description
The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Higher scores mean a worse outcome in the all domains.
Time Frame
Week 48
Title
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 12.
Description
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Time Frame
Week 12
Title
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 24.
Description
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Time Frame
Week 24
Title
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 36.
Description
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Time Frame
Week 36
Title
Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 48.
Description
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Time Frame
Week 48
Title
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 12.
Description
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Time Frame
Week 12
Title
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 24.
Description
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Time Frame
Week 24
Title
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 36.
Description
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Time Frame
Week 36
Title
Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 48.
Description
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Time Frame
Week 48
Title
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 12.
Description
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame
Week 12
Title
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 24.
Description
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame
Week 24
Title
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 36.
Description
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame
Week 36
Title
Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 48.
Description
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame
Week 48
Title
Change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at week 24.
Description
The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame
Week 24
Title
Change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at week 48.
Description
The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Week 0 is calculated, a negative value indicating improvement and a positive value worsening.
Time Frame
Week 48
Title
Change from baseline in Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) at week 24.
Description
The Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) is a disease-specific measure to assess the level of enthesitis in Ankylosing Spondylitis. It is based on clinical examination by assessor who determined by presence (score 1) or absence (score 0) of enthesitis at 13 different sites as below:
Both 1st costochondral
Both 7th costochondral
Both iliac crest
Both anterior superior iliac spine
Both posterior superior iliac spine
Both proximal Achilles tendon
5th lumbar spinous process
Time Frame
Week 24
Title
Change from baseline in Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) at week 48.
Description
The Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) is a disease-specific measure to assess the level of enthesitis in Ankylosing Spondylitis. It is based on clinical examination by assessor who determined by presence (score 1) or absence (score 0) of enthesitis at 13 different sites as below:
Both 1st costochondral
Both 7th costochondral
Both iliac crest
Both anterior superior iliac spine
Both posterior superior iliac spine
Both proximal Achilles tendon
5th lumbar spinous process
Time Frame
Week 48
Title
Change from baseline in swollen/tender joint count (0-44) at week 24.
Description
American College of Rheumatology (ACR), swollen joint count were an assessment of 44 joints. Joints are classified as either swollen or not swollen (tender or non-tender). An increase in swollen joints from baseline represented disease progression and/or joint worsening.
Time Frame
Week 24
Title
Change from baseline in swollen/tender joint count (0-44) at week 48.
Description
American College of Rheumatology (ACR), swollen joint count were an assessment of 44 joints. Joints are classified as either swollen or not swollen (tender or non-tender). An increase in swollen joints from baseline represented disease progression and/or joint worsening.
Time Frame
Week 48
Title
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 12.
Time Frame
Week 12
Title
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 24.
Time Frame
Week 24
Title
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 36.
Time Frame
Week 36
Title
Change from baseline in Erythrocyte sedimentation rate (ESR) at week 48.
Time Frame
Week 48
Title
Change from baseline in serum C-Reactive Protein (CRP) level at week 12.
Time Frame
Week 12
Title
Change from baseline in serum C-Reactive Protein (CRP) level at week 24.
Time Frame
Week 24
Title
Change from baseline in serum C-Reactive Protein (CRP) level at week 36.
Time Frame
Week 36
Title
Change from baseline in serum C-Reactive Protein (CRP) level at week 48.
Time Frame
Week 48
Title
Change from baseline in Assessment of SpondyloArthritis international Society (ASAS)-health index (ASAS-HI) at week 24.
Description
The self-report questionnaire measures functioning and health across 17 aspects of health and 9 environmental factors (EF) in patients with spondyloarthritis. The ASAS HI contains items addressing categories of pain, emotional functions, sleep, sexual function, mobility, self care, and community life.
Time Frame
Week 24
Title
Change from baseline in Assessment of SpondyloArthritis international Society (ASAS)-health index (ASAS-HI) at week 48.
Description
The self-report questionnaire measures functioning and health across 17 aspects of health and 9 environmental factors (EF) in patients with spondyloarthritis. The ASAS HI contains items addressing categories of pain, emotional functions, sleep, sexual function, mobility, self care, and community life.
Time Frame
Week 48
Title
Change from baseline in 5-level EQ-5D version (EQ-5D-5L) at week 24.
Description
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.
Time Frame
Week 24
Title
Change from baseline in 5-level EQ-5D version (EQ-5D-5L) at week 48.
Description
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.
Time Frame
Week 48
Title
The amount of NSAID intake between week 0 and 12
Description
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
Time Frame
From week 0 to week 12
Title
The amount of NSAID intake between week 12 and 24
Description
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
Time Frame
From week 12 to week 24
Title
The amount of NSAID intake between week 24 and 36
Description
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
Time Frame
From week 24 to week 36
Title
The amount of NSAID intake between week 36 and 48
Description
The general formula for the calculation is:
(equivalent NSAID score) × (days of intake during period of interest) × (days with intake per week)/(period of interest in days)
Equivalent NSAID score 0 = no intake 100 = 150mg diclofenac / 1000mg naproxen / 200mg aceclofenac / 400mg celecoxib / 600mg etodolac / 150mg indomethacin / 15mg meloxicam / 20mg piroxicam
A scale indicating days with intake per week 0 = did not take any NSAID in a week 0.5/7 = ≤1 day in a week 2/7 = >1 and ≤3 days in a week 4/7 = >3 and ≤5 days in a week 6/7 = >5 days in a week 1 = every day
days of intake during the period of interest
For example, if during a period of interest of 12 weeks, the patient has taken piroxicam 20 mg for 8 weeks and if during this 8-week period he has taken piroxicam 3-5 days per week the calculation is as follows:
100 (20 mg piroxicam score) × 56 (8 weeks) × 4/7 (3-5 days/week)/84 (12 weeks) = 38.1
Time Frame
From week 36 to week 48
Title
Percentage of patients at Least One Adverse Event (AE) During the study period.
Description
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame
From week 0 and week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Documented diagnosis of Ankylosing spondylitis (AS) and meet the modified New York classification criteria for AS.
Subjects maintaining stable disease (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] < 4) with standard-dose subcutaneous tumor-necrosis factor inhibitor (TNFi) treatment during previous 6 months from screening.
Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 at screening and 12 weeks prior to screening
In subjects treated with methotrexate or sulfasalazine, the dose should be maintained (methotrexate≤ 25mg/day, sulfasalazine ≤ 3 g/day) during previous 4 weeks before screening.
In subjects treated with systemic glucocorticoids, the dose should be less than 10mg/day of predinisolone or equivalent during at least 2 weeks from the screening
Subjects with stable dose of concomitant NSAID (including Cox2 inhibitors) during the 2 weeks from the randomization
Exclusion Criteria:
Exposure to more than 1 TNFi
History of hypersensitivity reaction to any TNFis
Subjects with concomitant fibromyalgia, as determined by the investigator
Subjects who have received any TNFis with reduced dosage
Presence of total spinal ankylosis ('Bamboo spine')
Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study
Subjects with a history of malignancies and lymphoproliferative disorder including lymphoma within 5 years (Basal cell carcinoma treated within previous 3 months and showing no evidence of recurrence, actinic keratosis, and treated cervical/colon carcinoma in situ were allowed.)
Subjects with current or history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac or neurological disease, as determined by the investigator
Subjects with significant laboratory abnormalities included but not limited to:
AST/ALT > 3.0 X ULN
White blood cell (WBC) < 3000/μL and/or absolute neutrophil count (ANC) < 1500/μL
Platelet count <100,000/μL and/or hemoglobin level <8.5 g/dL
Serum creatinine ≥ 1.5 X ULN
Subjected with any high-potency opioids (ex. methadone, hydromorphone, morphine, oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, meperidine)
Subjects with current acute or chronic viral hepatitis B or C or with human immunodeficiency virus (HIV) infection
Subjects planning to receive any live attenuated vaccinations after screening
Subjects has history of chronic alcohol abuse or drug abuse within 6 months from screening
Subjects concomitantly treated with systemic glucocorticoid (>10mg/day of prednisolone or equivalent doses)
Subjects with any other condition that, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tae-Hwan Kim, MD, PhD
Phone
82-2-2290-9245
Email
thkim@hanyang.ac.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Ji Hui Shin
Phone
82-2-2290-9252
Email
joobaraki77@naver.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tae-Hwan Kim, MD, PhD
Organizational Affiliation
Hanyang University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
REduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)
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