Axial Psoratic Arthritis
Conditions
Keywords
Assessment of spondyloarthritis international society, ASAS, axial, Psoriatic Arthritis, PsA, Magnetic resonance imaging, MRI
Brief summary
The purpose of this study is to demonstrate the efficacy and safety of secukinumab 150 mg or 300 mg in the management of axial manifestations in PsA patients who have failed to respond to at least 2 non-steroidal anti-inflammatory drugs (NSAIDs) over a 4-week period, according to assessment of spondyloarthritis international society (ASAS) recommendations for the treatment of axial spondyloarthritis (AxSpA).
Detailed description
In the anlalysis (CSR), there are 498 patients, as 5 patients were mis-randomized, i.e. had randomization number but did never take study medication. So there were 498 participants, and not 503
Interventions
BIOLOGICALSecukinumab
Anti IL-17a monoclonal antibody
DRUGSecukinumab and Placebo
Placebo matching AIN457
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
498 patients were randomized in this Phase 3b trial. 5 (of 503) were mis-randomized, i.e. received randomization number but never received study medication. This was a 52-week, randomized, double-blind, double-dummy, placebo-controlled, multicenter study to assess the efficacy of secukinumab 150 mg or 300 mg in patients with AxPsA who had an inadequate response to NSAIDs. The study had 2 treatment periods; a placebo-controlled period from Baseline to Week 12 followed by an active treatment period from Week 12 to Week 52. At Week 12, patients randomized to placebo at Baseline were re-randomized (1:1) to active treatment with secukinumab 150 mg or secukinumab 300 mg.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed * Diagnosis of psoriatic arthritis classified by Classification criteria for psoriatic arthritis (CASPAR) criteria * Active spinal disease defined by Bath ankylosing spondylitis disease activity index (BASDAI) score ≥ 4 * Spinal Pain visual analog scale (VAS) ≥ 40 (on a VAS 100 scale) * Inadequate Response to at least 2 non-steroidal anti-inflammatory drugs over a 4 weeks period
Exclusion criteria
* History of exposure to other IL-17 or IL-23 inhibitor biologic drug * History of exposure to previous biologic disease modifying anti-rheumatic drugs (DMARDs) (Tumor necrosis factor (TNF) blockers or Ustekinumab) * Current treatment with disease modifying anti-rheumatic drugs (DMARDs) other than Methotrexate * Subjects taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine) * Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician Other protocol-defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Response to Treatment (300 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | at week 12 | Purpose of this measure: was to demonstrate that secukinumab 150 mg s.c. is superior to placebo in the achievement of ASAS 20 response at Week 12 after superiority of 300 mg was established ASAS20 was defined as an improvement of ≥20% and absolute improvement of ≥10 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Response to Treatment (150 mg/300 mg AIN457) as Assessed by the ASAS40 Criteria at Week 12 | at week 12 | Proportion of patients with response to treatment as assessed by the Assessment of spondyloarthritis international society (ASAS) 40 criteria at week 12. ASAS40 was defined as an improvement of ≥40% and absolute improvement of ≥20 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI) |
| Percentage of Participants With Response to Treatment as Assessed by BASDAI50 at Week 12 | at week 12 | Bath ankylosing spondylitis disease activity index (BASDAI) 50 response BASDAI 50 response is defined as at least 50% improvement (decrease) in total BASDAI score. |
| Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Any Time | at baseline, at week 12 | Change from baseline in Spinal pain visual analog scale (VAS) at week 12 VAS is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom,pain,health) orientated from the left (worst) to the right (best). VAS measures pain and stress for on a horizontal line of 100 mm, ranging from very low (0) to very high (100). |
| Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Night | at baseline, at week 12 | Change from baseline in Spinal pain visual analog scale (VAS) at week 12 VAS is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom,pain,health) orientated from the left (worst) to the right (best). VAS measures pain and stress for on a horizontal line of 100 mm, ranging from very low (0) to very high (100) |
| Percentage of Participants With Response to Treatment (150 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | at week 12 | Purpose of this key secondary measure: was to demonstrate that secukinumab 150 mg s.c. is superior to placebo in the achievement of ASAS 20 response at Week 12 after superiority of 300 mg was established. 300mg and 150mg are presented side by side for clarity; and to align with protocol. 300mg data is for Primary outcome; and 150mg data is for key secondary outcome ASAS20 was defined as an improvement of ≥20% and absolute improvement of ≥10 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI) |
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | baseline and week 12 | The health assessment questionnaire disability index (HAQ-DI) assesses the difficulty a patient has had in the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question, level of difficulty is scored from 0 to 3 with 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. The score for each domain is the maximum (worst) score from the items/questions within the domain. Higher score indicates greater disability. Overall score was computed as the sum of the domain scores divided by the number of domains answered. The total possible score ranged from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 12 | baseline and week 12 | The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue with a 7-day recall period. Items are scored on a 0 - 4 response scale with anchors ranging from Not at all to Very much so. To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. |
| Change From Baseline in Spondyloarthritis International Society (ASAS) Health Index at Week 12 | baseline and week 12 | Statistical analysis (using ANCOVA) of change from baseline in spondyloarthritis international society (ASAS) Health Index score by visit - treatment period 1 ASAS HI is a disease-specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17-item instrument has scores ranging from 0 (good health) to 17 (poor health). Each item consists of one question that the participant needs to respond to with either I agree (score of 1) or I do not agree (score of 0). A score of 1 is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors |
| Percentage of Participants With Response to Treatment as Assessed by the ACR20 Criteria at Week 12 | at week 12 | American College of Rheumatology 20% (ACR20) Response at Week 12 is the % of responders with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS) |
| Change From Baseline Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index Score at Week 12 | baseline and week 12 | The Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index score range is 0-16, where 0 is the best outcome, and 16 the worst. The assessor determines whether the site shows tenderness and therefore would count as site with enthesitis. This is done by applying pressure to the site and getting feedback from patient about whether the site is tender. |
Countries
Belgium, Bulgaria, Czechia, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Poland, Romania, Russia, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
503 participants completed the screening period; and the randomized set consists of 498 patients because 5 participants were misrandomized
Pre-assignment details
95.6% of those randomized completed period 1 and moved on to period 2; and the 85.3% completed treatment period 2.
Participants by arm
| Arm | Count |
|---|---|
| AIN457 300mg Secukinumab 300 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 300 mg injections every 4 weeks between week 8 and week 48 | 167 |
| AIN457 150mg Secukinumab 150 mg sc injections at baseline and weekly until 4 weeks followed by Secukinumab 150 mg injections every 4 weeks between week 8 and week 48 | 165 |
| Placebo AIN457 Placebo sc. injections at baseline and weekly until Week 4, then at Week 8 and followed by Secukinumab 300 mg or 150 mg injections every 4 weeks between week 12 and week 48 | 166 |
| Total | 498 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 3 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Did not continue to period 2 | 5 | 12 | 0 | 0 | 5 |
| Overall Study | Lack of Efficacy | 7 | 4 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 3 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 2 | 3 | 7 | 0 |
Baseline characteristics
| Characteristic | AIN457 150mg | Placebo AIN457 | AIN457 300mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 156 Participants | 157 Participants | 159 Participants | 472 Participants |
| Age, Customized <45 years old | 65 Participants | 72 Participants | 77 Participants | 214 Participants |
| Age, Customized >=45 years old | 100 Participants | 94 Participants | 90 Participants | 284 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 10 Participants | 9 Participants | 6 Participants | 25 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 140 Participants | 146 Participants | 139 Participants | 425 Participants |
| Race/Ethnicity, Customized Not reported | 10 Participants | 8 Participants | 17 Participants | 35 Participants |
| Race/Ethnicity, Customized Unknown | 6 Participants | 0 Participants | 5 Participants | 13 Participants |
| Race/Ethnicity, Customized White | 159 Participants | 164 Participants | 162 Participants | 485 Participants |
| Sex: Female, Male Female | 84 Participants | 78 Participants | 90 Participants | 252 Participants |
| Sex: Female, Male Male | 81 Participants | 88 Participants | 77 Participants | 246 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 248 | 0 / 245 | 0 / 166 |
| other Total, other adverse events | 116 / 248 | 108 / 245 | 47 / 166 |
| serious Total, serious adverse events | 14 / 248 | 14 / 245 | 4 / 166 |
Outcome results
Primary
Percentage of Participants With Response to Treatment (300 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12
Purpose of this measure: was to demonstrate that secukinumab 150 mg s.c. is superior to placebo in the achievement of ASAS 20 response at Week 12 after superiority of 300 mg was established ASAS20 was defined as an improvement of ≥20% and absolute improvement of ≥10 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI)
Time frame: at week 12
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 150mg | Percentage of Participants With Response to Treatment (300 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | 66.3 percentage of participants |
| AIN457 300mg | Percentage of Participants With Response to Treatment (300 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | 62.9 percentage of participants |
| Placebo AIN457 | Percentage of Participants With Response to Treatment (300 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | 31.2 percentage of participants |
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [2.72, 7.01]Regression, Logistic
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [2.41, 6.1]Regression, Logistic
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 12
The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue with a 7-day recall period. Items are scored on a 0 - 4 response scale with anchors ranging from Not at all to Very much so. To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52.
Time frame: baseline and week 12
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AIN457 150mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 12 | 8.0 scores on a scale | Standard Error 0.72 |
| AIN457 300mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 12 | 7.6 scores on a scale | Standard Error 0.71 |
| Placebo AIN457 | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 12 | 4.2 scores on a scale | Standard Error 0.7 |
Comparison: week 12p-value: 0.000295% CI: [1.8, 5.7]ANCOVA
Comparison: week 12p-value: 0.000795% CI: [1.4, 5.3]ANCOVA
Secondary
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12
The health assessment questionnaire disability index (HAQ-DI) assesses the difficulty a patient has had in the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question, level of difficulty is scored from 0 to 3 with 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. The score for each domain is the maximum (worst) score from the items/questions within the domain. Higher score indicates greater disability. Overall score was computed as the sum of the domain scores divided by the number of domains answered. The total possible score ranged from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability.
Time frame: baseline and week 12
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AIN457 150mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | -0.330 scores on a scale | Standard Error 0.036 |
| AIN457 300mg | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | -0.389 scores on a scale | Standard Error 0.0353 |
| Placebo AIN457 | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 | -0.155 scores on a scale | Standard Error 0.0351 |
p-value: 0.000595% CI: [-0.273, -0.076]ANCOVA
p-value: <0.000195% CI: [-0.331, -0.136]ANCOVA
Secondary
Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Any Time
Change from baseline in Spinal pain visual analog scale (VAS) at week 12 VAS is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom,pain,health) orientated from the left (worst) to the right (best). VAS measures pain and stress for on a horizontal line of 100 mm, ranging from very low (0) to very high (100).
Time frame: at baseline, at week 12
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AIN457 150mg | Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Any Time | -28.5 scores on a scale | Standard Error 1.88 |
| AIN457 300mg | Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Any Time | -26.5 scores on a scale | Standard Error 1.84 |
| Placebo AIN457 | Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Any Time | -13.6 scores on a scale | Standard Error 1.83 |
p-value: <0.000195% CI: [-20, -9.7]ANCOVA
p-value: <0.000195% CI: [-18, -7.8]ANCOVA
Secondary
Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Night
Change from baseline in Spinal pain visual analog scale (VAS) at week 12 VAS is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom,pain,health) orientated from the left (worst) to the right (best). VAS measures pain and stress for on a horizontal line of 100 mm, ranging from very low (0) to very high (100)
Time frame: at baseline, at week 12
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AIN457 150mg | Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Night | -30.3 scores on a scale | Standard Error 1.95 |
| AIN457 300mg | Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Night | -30.2 scores on a scale | Standard Error 1.9 |
| Placebo AIN457 | Change From Baseline in Spinal Pain Visual Analog Scale (VAS) - Pain at Night | -15.2 scores on a scale | Standard Error 1.89 |
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [-20.4, -9.7]ANCOVA
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [-20.3, -9.8]ANCOVA
Secondary
Change From Baseline in Spondyloarthritis International Society (ASAS) Health Index at Week 12
Statistical analysis (using ANCOVA) of change from baseline in spondyloarthritis international society (ASAS) Health Index score by visit - treatment period 1 ASAS HI is a disease-specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17-item instrument has scores ranging from 0 (good health) to 17 (poor health). Each item consists of one question that the participant needs to respond to with either I agree (score of 1) or I do not agree (score of 0). A score of 1 is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors
Time frame: baseline and week 12
Population: Full analysis set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AIN457 150mg | Change From Baseline in Spondyloarthritis International Society (ASAS) Health Index at Week 12 | -2.9 scores on a scale | Standard Error 0.29 |
| AIN457 300mg | Change From Baseline in Spondyloarthritis International Society (ASAS) Health Index at Week 12 | -2.8 scores on a scale | Standard Error 0.28 |
| Placebo AIN457 | Change From Baseline in Spondyloarthritis International Society (ASAS) Health Index at Week 12 | -1.2 scores on a scale | Standard Error 0.28 |
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [-2.5, -0.9]ANCOVA
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [-2.4, -0.9]ANCOVA
Secondary
Change From Baseline Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index Score at Week 12
The Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index score range is 0-16, where 0 is the best outcome, and 16 the worst. The assessor determines whether the site shows tenderness and therefore would count as site with enthesitis. This is done by applying pressure to the site and getting feedback from patient about whether the site is tender.
Time frame: baseline and week 12
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AIN457 150mg | Change From Baseline Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index Score at Week 12 | -2.2 scores on a scale | Standard Error 0.22 |
| AIN457 300mg | Change From Baseline Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index Score at Week 12 | -2.4 scores on a scale | Standard Error 0.21 |
| Placebo AIN457 | Change From Baseline Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index Score at Week 12 | -1.7 scores on a scale | Standard Error 0.21 |
p-value: 0.097195% CI: [-1.1, 0.1]ANCOVA
p-value: 0.020795% CI: [-1.3, -0.1]ANCOVA
Secondary
Percentage of Participants With Response to Treatment (150 mg/300 mg AIN457) as Assessed by the ASAS40 Criteria at Week 12
Proportion of patients with response to treatment as assessed by the Assessment of spondyloarthritis international society (ASAS) 40 criteria at week 12. ASAS40 was defined as an improvement of ≥40% and absolute improvement of ≥20 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI)
Time frame: at week 12
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 150mg | Percentage of Participants With Response to Treatment (150 mg/300 mg AIN457) as Assessed by the ASAS40 Criteria at Week 12 | 39.5 percentage of participants |
| AIN457 300mg | Percentage of Participants With Response to Treatment (150 mg/300 mg AIN457) as Assessed by the ASAS40 Criteria at Week 12 | 43.6 percentage of participants |
| Placebo AIN457 | Percentage of Participants With Response to Treatment (150 mg/300 mg AIN457) as Assessed by the ASAS40 Criteria at Week 12 | 12.2 percentage of participants |
p-value: <0.000195% CI: [3.2, 9.84]Regression, Logistic
p-value: <0.000195% CI: [2.67, 8.33]Regression, Logistic
Secondary
Percentage of Participants With Response to Treatment (150 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12
Purpose of this key secondary measure: was to demonstrate that secukinumab 150 mg s.c. is superior to placebo in the achievement of ASAS 20 response at Week 12 after superiority of 300 mg was established. 300mg and 150mg are presented side by side for clarity; and to align with protocol. 300mg data is for Primary outcome; and 150mg data is for key secondary outcome ASAS20 was defined as an improvement of ≥20% and absolute improvement of ≥10 unit (0-100 mm VAS) from baseline in ≥3 of the following 4 domains (and absence of deterioration in any domain): patient's global assessment of disease activity (PTGA), pain assessment (total pain score), Bath Ankylosing Spondylitis Functional Index (BASFI), and clinical inflammation (mean of 2 morning stiffness-related scores on the BASDAI)
Time frame: at week 12
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 150mg | Percentage of Participants With Response to Treatment (150 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | 66.3 percentage of participants |
| AIN457 300mg | Percentage of Participants With Response to Treatment (150 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | 62.9 percentage of participants |
| Placebo AIN457 | Percentage of Participants With Response to Treatment (150 mg AIN457) as Assessed by the ASAS20 Criteria at Week 12 | 31.2 percentage of participants |
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [2.72, 7.01]Regression, Logistic
Secondary
Percentage of Participants With Response to Treatment as Assessed by BASDAI50 at Week 12
Bath ankylosing spondylitis disease activity index (BASDAI) 50 response BASDAI 50 response is defined as at least 50% improvement (decrease) in total BASDAI score.
Time frame: at week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 150mg | Percentage of Participants With Response to Treatment as Assessed by BASDAI50 at Week 12 | 32.7 percentage of particiapnts |
| AIN457 300mg | Percentage of Participants With Response to Treatment as Assessed by BASDAI50 at Week 12 | 37.4 percentage of particiapnts |
| Placebo AIN457 | Percentage of Participants With Response to Treatment as Assessed by BASDAI50 at Week 12 | 9.8 percentage of particiapnts |
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [2.43, 8.33]Regression, Logistic
Comparison: Up to week 12, all participants in the group placebo AIN457 took placebo onlyp-value: <0.000195% CI: [3.04, 10.21]Regression, Logistic
Secondary
Percentage of Participants With Response to Treatment as Assessed by the ACR20 Criteria at Week 12
American College of Rheumatology 20% (ACR20) Response at Week 12 is the % of responders with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS)
Time frame: at week 12
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 150mg | Percentage of Participants With Response to Treatment as Assessed by the ACR20 Criteria at Week 12 | 56.5 percentage of participants |
| AIN457 300mg | Percentage of Participants With Response to Treatment as Assessed by the ACR20 Criteria at Week 12 | 51.6 percentage of participants |
| Placebo AIN457 | Percentage of Participants With Response to Treatment as Assessed by the ACR20 Criteria at Week 12 | 18.5 percentage of participants |
p-value: <0.000195% CI: [3.31, 9.95]Regression, Logistic
p-value: <0.000195% CI: [2.83, 8.16]Regression, Logistic