Psoriatic Arthritis
Conditions
Keywords
Psoriatic Arthritis, Arthritis, Psoriatic, Psoriatic Arthropathy, Spondylitis
Brief summary
The purpose of this study was to demonstrate efficacy including effect on inhibition of progression of structural damage, safety and tolerability up to 2 years with primary focus at Week 16 (week 24 for structural damage), to support the use of secukinumab pre-filled syringe (PFS) by subcutaneous (s.c.) self-administration with or without loading regimen in subjects with active Psoriatic Arthritis (PsA) despite current or previous NSAID, DMARD therapy and/or previous anti-TNFα therapy. Long term efficacy up to 2 years was based on signs and symptoms of joint/bone structure preservation (X-ray) and improvement in physical function measured by Health Assessment Questionnaire - Disability Index (HAQ-DI©), as well as skin and nail improvement for psoriasis signs.
Detailed description
This multicenter study uses a randomized, double-blind, placebo-controlled, parallel-group design. A screening period (SCR) running up to 10 weeks before randomization will be used to assess subject eligibility followed by 104 weeks of treatment. At BSL approximately 990 subjects whose eligibility is confirmed will be randomized to one of four treatment groups in 2:2:2:3 ratio: * Group 1 - secukinumab 150 mg s.c. without loading regimen * Group 2 - secukinumab 150 mg s.c. with loading dose regimen * Group 3 - secukinumab 300 mg s.c. with loading dose regimen * Group 4 - Placebo s.c. NOTE: Group 4 is split into 2 treatment arms, detailed description below. At randomization, subjects will be stratified on the basis of previous anti-TNF therapy as TNFα inhibitor naïve (TNF-naïve) or TNFα inhibitor inadequate responders (TNF-IR). At each study treatment visit, one (for secukinumab 150 mg) or two (for secukinumab 300 mg) s.c. injections in the form of PFS will be administered, since secukinumab is available in 1.0 mL (150 mg) PFSs. Placebo to secukinumab is also available in 1.0 mL to match the active drug. At Week 16, subjects who have been randomized to secukinumab groups at BSL (Groups 1-3) will be classified as either responders (≥20% improvement from BSL in both tender joint count (TJC) and swollen joint counts (SJC)) or non-responders (\<20% improvement from BSL TJC or SJC), however they will continue on the same treatment irrespective of their response status. At Week 16, subjects who have been randomized to placebo at BSL (Group 4) will be classified as either responders (≥20% improvement from BSL in both TJC and SJC) or non-responders (\<20% improvement from BSL TJC or SJC): * Subjects who are non-responders will receive either secukinumab 150 mg or 300 mg s.c. every 4 weeks starting at Week 16 (as dictated by treatment sequence assigned to these subjects at BSL). * Subjects who are responders will continue to receive placebo every 4 weeks. Starting Week 24, these subjects will receive either secukinumab 150 mg s.c. or 300 mg s.c. every 4 weeks starting at Week 24 (as dictated by treatment sequence assigned to these subjects at BSL). At Week 24, the assessments to address the primary objective will be performed. As described above, subjects who are still receiving placebo s.c. injection will receive either secukinumab 150 mg s.c. or 300 mg s.c. every 4 weeks starting at Week 24 (as dictated by treatment sequence assigned to these subjects at BSL). At week 52, based on Investigator's decision, the subjects on a 150 mg dose whose signs and symptoms do not show satisfactory response have the possibility to be allocated to secukinumab 300 mg s.c. After the Week 52 database lock and analyses have been completed, site personnel and subjects will be unblinded to the original randomized treatment (sequence) assignment at randomization. In addition, treatment will be given open-label in order to eliminate the placebo injection. The subject will continue to receive the same active dose of secukinumab as open-label treatment administered until Week 100.
Interventions
BIOLOGICALSecukinumab
Anti IL-17a monoclonal antibody
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at BSL ≥3 tender joints out of 78 and ≥3 swollen joints out of 76 (dactylitis of a digit counts as one joint each). * Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies negative at screening. * Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a documented history of plaque psoriasis. * Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs.-Subjects who are regularly taking NSAIDs as part of their PsA therapy are required to be on a stable dose for at least 2 weeks before study randomization and should remain on a stable dose up to Week 24. * Subjects taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week 24. * Subjects taking MTX (≤ 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week 52. * Subjects on MTX must be on folic acid supplementation at randomization. * Subjects who are on a DMARD other than MTX must discontinue the DMARD 4 weeks prior to randomization visit except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed. * Subjects who have been on a TNFα inhibitor must have experienced an inadequate response to previous or current treatment with a TNFα inhibitor given at an approved dose for at least 3 months or have stopped treatment due to safety/tolerability problems after at least one administration of a TNFα inhibitor. * Subjects who have previously been treated with TNFα inhibitors (investigational or approved) will be allowed entry into study after appropriate wash-out period prior to randomization
Exclusion criteria
Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process. - Subjects taking high potency opioid analgesics. * Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor. - Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. * Any intramuscular or intravenous or intra-articular corticosteroid treatment within 4 weeks before randomization. * Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα (investigational or approved). * Previous treatment with any cell-depleting therapies including but not limited to anti- CD20, investigational agents * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16 | Week 16 | ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement based on tender 78-joint count, swollen 76-joint count and at least 20% improvement in 3 of the following 5 measures: participant's assessment of PsA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, participant's self-assessed disability (Health Assessment Questionnaire Disability Index (HAQ-DI) score), and acute phase reactant evaluated as (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR)). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response | Week 16 | The efficacy of secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo based on the proportion of patients achieving Psoriatic Area and Severity Index 75 (PASI75) response. |
| Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response | 16 weeks | The efficacy of secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo based on the proportion of patients achieving Psoriatic Area and Severity Index 90 (PASI90) response. |
| Count and Percentage of Patients Achieving an ACR50 Response | 16 weeks | ACR 50 Response is a measure based on American College of Rheumatology criteria of at least a 50% improvement in the number of tender and swollen joints, and a 50% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function measured using the Stanford Health Assessment Questionnaire the physician's global assessment of disease status; serum C-reactive protein levels. |
| Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | Baseline, Week 24 | PsA modified vdH-mTSS scoring method was used to assess bone erosion & joint space narrowing (JSN) in hands & feet; that included the 2nd through 5th distal interphalangeal (DIP) joints of each hand. Maximum score for erosions was 5 in joints of the hands and 10 in joints of the feet with 0=no erosions, 1=discrete erosion, 2=large erosion not passing the mid-line, and 3=large erosion passing the mid-line. JSN is: 0=normal, 1=asymmetrical or minimal narrowing up to a maximum of 25%, 2 = definite narrowing with loss of up to 50% of the normal space, 3 = definite narrowing with loss of 50-99% of the normal space, and 4 = absence of a joint space. Maximum erosion score is 320 (200 for the hands and 120 for the feet), and the max total JSN score is 208 (160 for the hands and 48 for the feet). Total radiographic score (hands & feet combined) ranges from 0 to 528, where higher scores indicate more articular damage |
| Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP)) | 16 weeks | The improvement on secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo for the disease activity assessed by the changes in Disease Activity Score for 28 joints (DAS28-CRP) (utilizing High sensitivity C-Reactive Protein (hsCRP)) relative to baseline. Scores range from 0 (no difficulty) to 3 (unable to do) |
| Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline | 16 weeks | The efficacy of secukinumab pooled regimen (150 mg with or without loading regimen, and 300 mg with loading regimen) at Week 16 compared with placebo based on the proportion of patients with enthesitis in the subset of patients who had enthesitis at baseline |
| Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline | 16 weeks | The efficacy of secukinumab pooled regimen (150 mg with or without loading regimen, and 300 mg with loading regimen) at Week 16 compared with placebo based on the proportion of patients with dactylitis in the subset of patients who have dactylitis at baseline |
| Change From Baseline in HAQ-DI© Score | 16 weeks | The change (within treatment) on secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen), at Week 16 compared with placebo for the disease activity assessed by the changes in The Health Assessment Questionnaire disability index (HAQ-DI) relative to baseline. |
Countries
Argentina, Austria, Canada, Chile, Czechia, Denmark, Estonia, Finland, Germany, Greece, Guatemala, Hungary, India, Ireland, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, Philippines, Russia, Spain, Sweden, Thailand, United Kingdom, United States, Vietnam
Participant flow
Recruitment details
Study was conducted at 173 centers in 28 countries.
Pre-assignment details
996 were randomized and dosed, of which 932 participants completed 24 weeks of treatment. Out of the 64 participants who discontinued the most common reasons were participant/guardian decision (32) and adverse events (16).
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 150 mg Without Load Participants were s.c. administered with 150 milligrams (mg) of secukinumab as 1 mL PFS and secukinumab matching placebo (1 mL PFS) at baseline. Participants received secukinumab matching placebo (2\*1 mL PFS) at Weeks 1, 2 and 3. From week 4 participants received secukinumab 150 mg (1 mL PFS) and secukinumab matching placebo (1 mL PFS) every four weeks up to 100 weeks. | 222 |
| Secukinumab 150 mg With Load Participants were s.c. administered with 150 mg of secukinumab as 1 mL PFS and secukinumab matching placebo (1 mL PFS) at baseline, weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4 up to 100. | 220 |
| Secukinumab 300 mg With Load Participants were s.c. administered with 300 mg of secukinumab as 2\*1 mL PFS (150 mg dose) at baseline, weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4 up to 100 weeks. | 222 |
| Placebo Participants were s.c. administered with secukinumab matching placebo (2\*1 mL PFS) at baseline, weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4. Participants were further randomized to two different treatment sequences in 1:1 ratio at baseline as secukinumab matching placebo till Week 16/24 followed by secukinumab 150 mg every 4 weeks starting at Week 16/24 up to 100 weeks and secukinumab matching placebo till Week 16/24 followed by secukinumab 300 mg every 4 weeks starting at Week 16/24 up to 100 weeks. | 332 |
| Total | 996 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 3 | 9 |
| Overall Study | Due to Non-compliance with treatment | 0 | 0 | 0 | 1 |
| Overall Study | Due to Technical problems | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 1 | 0 | 3 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 2 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 3 | 3 | 19 |
Baseline characteristics
| Characteristic | Secukinumab 150 mg Without Load | Secukinumab 150 mg With Load | Secukinumab 300 mg With Load | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.8 years STANDARD_DEVIATION 11.82 | 48.4 years STANDARD_DEVIATION 12.87 | 48.9 years STANDARD_DEVIATION 12.8 | 49.0 years STANDARD_DEVIATION 12.12 | 48.8 years STANDARD_DEVIATION 12.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 30 Participants | 31 Participants | 51 Participants | 137 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 180 Participants | 160 Participants | 174 Participants | 251 Participants | 765 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants | 30 Participants | 17 Participants | 30 Participants | 94 Participants |
| Sex: Female, Male Female | 102 Participants | 109 Participants | 114 Participants | 171 Participants | 496 Participants |
| Sex: Female, Male Male | 120 Participants | 111 Participants | 108 Participants | 161 Participants | 500 Participants |
| Subjects with psoriasis ≥ 3% of BSA No | 105 Participants | 95 Participants | 112 Participants | 170 Participants | 482 Participants |
| Subjects with psoriasis ≥ 3% of BSA Yes | 117 Participants | 125 Participants | 110 Participants | 162 Participants | 514 Participants |
| Subjects with psoriasis of hands and feet No | 89 Participants | 85 Participants | 95 Participants | 158 Participants | 427 Participants |
| Subjects with psoriasis of hands and feet Yes | 133 Participants | 135 Participants | 127 Participants | 174 Participants | 569 Participants |
| Subjects with psoriasis of nail No | 69 Participants | 85 Participants | 78 Participants | 101 Participants | 333 Participants |
| Subjects with psoriasis of nail Yes | 153 Participants | 135 Participants | 144 Participants | 231 Participants | 663 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 222 | 0 / 220 | 0 / 222 | 0 / 822 | 0 / 332 |
| other Total, other adverse events | 95 / 222 | 82 / 220 | 83 / 222 | 275 / 822 | 127 / 332 |
| serious Total, serious adverse events | 6 / 222 | 9 / 220 | 7 / 222 | 25 / 822 | 12 / 332 |
Outcome results
Primary
Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16
ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement based on tender 78-joint count, swollen 76-joint count and at least 20% improvement in 3 of the following 5 measures: participant's assessment of PsA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, participant's self-assessed disability (Health Assessment Questionnaire Disability Index (HAQ-DI) score), and acute phase reactant evaluated as (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR)).
Time frame: Week 16
Population: The analysis was performed in Full Analysis Set (FAS) population defined as all randomized participants assigned to study treatment. Following the intent-to-treat principle, participants were analyzed according to treatment assigned at randomization by actual anti-Tumor Necrosis Factor (TNF) status. Missing responses were imputed as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 150 mg Without Load | Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16 | 59.5 percentage of participants |
| Secukinumab 150 mg With Load | Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16 | 55.5 percentage of participants |
| Secukinumab 300 mg With Load | Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16 | 62.6 percentage of participants |
| Placebo | Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16 | 27.4 percentage of participants |
Comparison: Statistical values were calculated from a logistic regression model with treatment and randomization stratum (TNF-a status -naive or Incidence Rate) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [2.78, 5.79]Regression, Logistic
Comparison: Statistical values were calculated from a logistic regression model with treatment and randomization stratum (TNF-a status -naive or Incidence Rate) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [2.35, 4.87]Regression, Logistic
Comparison: Statistical values were calculated from a logistic regression model with treatment and randomization stratum (TNF-a status -naive or Incidence Rate) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [3.16, 6.63]Regression, Logistic
Secondary
Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP))
The improvement on secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo for the disease activity assessed by the changes in Disease Activity Score for 28 joints (DAS28-CRP) (utilizing High sensitivity C-Reactive Protein (hsCRP)) relative to baseline. Scores range from 0 (no difficulty) to 3 (unable to do)
Time frame: 16 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg Without Load | Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP)) | -1.29 scores on a scale | Standard Error 0.074 |
| Secukinumab 150 mg With Load | Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP)) | -1.29 scores on a scale | Standard Error 0.075 |
| Secukinumab 300 mg With Load | Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP)) | -1.49 scores on a scale | Standard Error 0.074 |
| Placebo | Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing High Sensitivity C-Reactive Protein (hsCRP)) | -0.63 scores on a scale | Standard Error 0.062 |
Comparison: Mixed model with treatment regimen, analysis visit and randomization stratum (TNF-alpha status -naïve or IR) as factors, weight and baseline score as continuous covariates, and treatment by analysis visit and baseline score by analysis visit as interaction terms, using an unstructured covariance structurep-value: <0.000195% CI: [-0.85, -0.47]Mixed Models Analysis
Comparison: Mixed model with treatment regimen, analysis visit and randomization stratum (TNF-alpha status -naïve or IR) as factors, weight and baseline score as continuous covariates, and treatment by analysis visit and baseline score by analysis visit as interaction terms, using an unstructured covariance structurep-value: <0.000195% CI: [-0.85, -0.47]Mixed Models Analysis
Comparison: Mixed model with treatment regimen, analysis visit and randomization stratum (TNF-alpha status -naïve or IR) as factors, weight and baseline score as continuous covariates, and treatment by analysis visit and baseline score by analysis visit as interaction terms, using an unstructured covariance structurep-value: <0.000195% CI: [-1.05, -0.67]Mixed Models Analysis
Secondary
Change From Baseline in HAQ-DI© Score
The change (within treatment) on secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen), at Week 16 compared with placebo for the disease activity assessed by the changes in The Health Assessment Questionnaire disability index (HAQ-DI) relative to baseline.
Time frame: 16 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg Without Load | Change From Baseline in HAQ-DI© Score | -0.45 scores on a scale | Standard Error 0.035 |
| Secukinumab 150 mg With Load | Change From Baseline in HAQ-DI© Score | -0.44 scores on a scale | Standard Error 0.035 |
| Secukinumab 300 mg With Load | Change From Baseline in HAQ-DI© Score | -0.55 scores on a scale | Standard Error 0.035 |
| Placebo | Change From Baseline in HAQ-DI© Score | -0.21 scores on a scale | Standard Error 0.029 |
p-value: <0.000195% CI: [-0.32, -0.15]Mixed Models Analysis
p-value: <0.000195% CI: [-0.32, -0.14]Mixed Models Analysis
p-value: <0.000195% CI: [-0.42, -0.24]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS))
PsA modified vdH-mTSS scoring method was used to assess bone erosion & joint space narrowing (JSN) in hands & feet; that included the 2nd through 5th distal interphalangeal (DIP) joints of each hand. Maximum score for erosions was 5 in joints of the hands and 10 in joints of the feet with 0=no erosions, 1=discrete erosion, 2=large erosion not passing the mid-line, and 3=large erosion passing the mid-line. JSN is: 0=normal, 1=asymmetrical or minimal narrowing up to a maximum of 25%, 2 = definite narrowing with loss of up to 50% of the normal space, 3 = definite narrowing with loss of 50-99% of the normal space, and 4 = absence of a joint space. Maximum erosion score is 320 (200 for the hands and 120 for the feet), and the max total JSN score is 208 (160 for the hands and 48 for the feet). Total radiographic score (hands & feet combined) ranges from 0 to 528, where higher scores indicate more articular damage
Time frame: Baseline, Week 24
Population: The analysis was performed in FAS population with a measurement that could be evaluated. Participants in placebo group, rescued at Week 16 were also extrapolated (i.e. treated as missing at Week 24).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secukinumab 150 mg Without Load | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | baseline | 15.25 Mean Sharp Score | Standard Deviation 37.098 |
| Secukinumab 150 mg Without Load | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | change | -0.10 Mean Sharp Score | Standard Deviation 2.872 |
| Secukinumab 150 mg With Load | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | change | 0.13 Mean Sharp Score | Standard Deviation 1.222 |
| Secukinumab 150 mg With Load | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | baseline | 13.50 Mean Sharp Score | Standard Deviation 25.636 |
| Secukinumab 300 mg With Load | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | baseline | 12.90 Mean Sharp Score | Standard Deviation 23.781 |
| Secukinumab 300 mg With Load | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | change | 0.02 Mean Sharp Score | Standard Deviation 1.336 |
| Placebo | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | baseline | 14.95 Mean Sharp Score | Standard Deviation 38.236 |
| Placebo | Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)) | change | 0.50 Mean Sharp Score | Standard Deviation 1.708 |
Comparison: Secukinumab 300 mg With Load compared to Placebo Estimate (for the difference in mean), SE and p-value are from a non-parametric ANCOVA model (Koch, 1998) with the change from baseline van der Heijde total modified Sharp score (or Erosion Score or Joint Space Narrowing Score) as the dependent variable, treatment and randomization stratum (TNFa status -naive or IR ) as factors, and weight and baseline van der Heijde total modified Sharp score as covariates.p-value: 0.0061Non-parametric ANCOVA model
Comparison: Secukinumab 300 mg With Load compared to Placebo Estimate (for the difference in mean), SE and p-value are from a non-parametric ANCOVA model (Koch, 1998) with the change from baseline van der Heijde total modified Sharp score (or Erosion Score or Joint Space Narrowing Score) as the dependent variable, treatment and randomization stratum (TNFa status -naive or IR ) as factors, and weight and baseline van der Heijde total modified Sharp score as covariates.p-value: 0.0048Non-parametric ANCOVA model
Comparison: Secukinumab 300 mg With Load compared to Placebo Estimate (for the difference in mean), SE and p-value are from a non-parametric ANCOVA model (Koch, 1998) with the change from baseline van der Heijde total modified Sharp score (or Erosion Score or Joint Space Narrowing Score) as the dependent variable, treatment and randomization stratum (TNFa status -naive or IR ) as factors, and weight and baseline van der Heijde total modified Sharp score as covariates.p-value: 0.0003Non-parametric ANCOVA model
Secondary
Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline
The efficacy of secukinumab pooled regimen (150 mg with or without loading regimen, and 300 mg with loading regimen) at Week 16 compared with placebo based on the proportion of patients with dactylitis in the subset of patients who have dactylitis at baseline
Time frame: 16 weeks
Population: Dactylitis subset: The dactylitis subset included all FAS patients who had dactylitis at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg Without Load | Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline | 45 Participants |
| Secukinumab 150 mg With Load | Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline | 34 Participants |
| Secukinumab 300 mg With Load | Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline | 28 Participants |
| Placebo | Count and Percentage of Participants With Dactylitis in the Subset of Patients Who Have Dactylitis at Baseline | 84 Participants |
p-value: 0.000495% CI: [0.22, 0.65]Regression, Logistic
p-value: 0.000395% CI: [0.19, 0.6]Regression, Logistic
p-value: <0.000195% CI: [0.13, 0.44]Regression, Logistic
Secondary
Count and Percentage of Patients Achieving an ACR50 Response
ACR 50 Response is a measure based on American College of Rheumatology criteria of at least a 50% improvement in the number of tender and swollen joints, and a 50% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function measured using the Stanford Health Assessment Questionnaire the physician's global assessment of disease status; serum C-reactive protein levels.
Time frame: 16 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg Without Load | Count and Percentage of Patients Achieving an ACR50 Response | 71 Participants |
| Secukinumab 150 mg With Load | Count and Percentage of Patients Achieving an ACR50 Response | 79 Participants |
| Secukinumab 300 mg With Load | Count and Percentage of Patients Achieving an ACR50 Response | 88 Participants |
| Placebo | Count and Percentage of Patients Achieving an ACR50 Response | 27 Participants |
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [3.3, 8.73]Regression, Logistic
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [3.93, 10.32]Regression, Logistic
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [4.61, 12]Regression, Logistic
Secondary
Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response
The efficacy of secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo based on the proportion of patients achieving Psoriatic Area and Severity Index 75 (PASI75) response.
Time frame: Week 16
Population: Psoriasis subset: The psoriasis subset included all FAS patients who had ≥ 3% of the BSA affected by psoriatic skin involvement at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg Without Load | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response | 68 Participants |
| Secukinumab 150 mg With Load | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response | 75 Participants |
| Secukinumab 300 mg With Load | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response | 77 Participants |
| Placebo | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 75 (PASI75) Response | 20 Participants |
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [5.52, 18.63]Regression, Logistic
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [6.37, 21.37]Regression, Logistic
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.p-value: <0.000195% CI: [9.56, 34.12]Regression, Logistic
Secondary
Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response
The efficacy of secukinumab 150 mg (with or without loading regimen), or 300 mg (with loading regimen) at Week 16 compared with placebo based on the proportion of patients achieving Psoriatic Area and Severity Index 90 (PASI90) response.
Time frame: 16 weeks
Population: Psoriasis subset: The psoriasis subset included all FAS patients who had ≥ 3% of the BSA affected by psoriatic skin involvement at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg Without Load | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response | 37 Participants |
| Secukinumab 150 mg With Load | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response | 46 Participants |
| Secukinumab 300 mg With Load | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response | 59 Participants |
| Placebo | Count and Percentage of Patients Achieving Psoriatic Area and Severity Index 90 (PASI90) Response | 15 Participants |
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.~Missing responses are imputed as non-responders.p-value: <0.000195% CI: [2.31, 8.83]Regression, Logistic
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.~Missing responses are imputed as non-responders.p-value: <0.000195% CI: [3.18, 11.87]Regression, Logistic
Comparison: Odds ratio, 95% confidence interval, and p-value are from a logistic regression model with treatment and randomization stratum (TNF-alpha status -naïve or IR) as factors and baseline weight as a covariate.~Missing responses are imputed as non-responders.p-value: <0.000195% CI: [6.43, 24.48]Regression, Logistic
Secondary
Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline
The efficacy of secukinumab pooled regimen (150 mg with or without loading regimen, and 300 mg with loading regimen) at Week 16 compared with placebo based on the proportion of patients with enthesitis in the subset of patients who had enthesitis at baseline
Time frame: 16 weeks
Population: Enthesitis subset: The enthesitis subset included all FAS patients who had enthesitis at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg Without Load | Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline | 75 Participants |
| Secukinumab 150 mg With Load | Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline | 64 Participants |
| Secukinumab 300 mg With Load | Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline | 62 Participants |
| Placebo | Count and Percentage of Patients With Enthesitis in the Subset of Patients Who Had Enthesitis at Baseline | 124 Participants |
p-value: 0.22595% CI: [0.47, 1.19]Regression, Logistic
p-value: 0.000495% CI: [0.29, 0.7]Regression, Logistic
p-value: 0.000495% CI: [0.28, 0.69]Regression, Logistic