Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, RA, secukinumab, AIN457, inflammatory joints, American College of Rheumatology, ACR
Brief summary
The study compared the efficacy and assessed the safety of secukinumab given as 3 intravenous (i.v.) loading doses or weekly sub-cutaneous (s.c.) loading doses, compared to placebo, followed by monthly s.c. injections in patients with active Rheumatoid Arthritis (RA) despite treatment with Methotrexate.
Interventions
BIOLOGICALsecukinumab (AIN457)
Secukinumab is a human monoclonal antibody. Monoclonal antibodies are proteins that recognize and bind to unique proteins that your body produces. Secukinumab binds and reduces the activity of a cytokine (a messenger protein in the body) called Interleukin 17 (IL-17).
DRUGplacebo
Matching placebo to AIN457 i.v. and to AIN457 s.c..
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* presence of RA classified by ACR 2010 revised criteria for at least 3 months before screening * must have been taking MTX for at least 3 months before randomization and must currently be on a stable dose of MTX for at least 4 weeks before randomization. * At Baseline: Disease activity criteria defined by \>6 tender joints out of 68 and \>6 swollen joints out of 66 and with at least 1 of the following at screening: Anti-CCP antibodies positive OR Rheumatoid Factor positive and with at least 1 of the following at screening: hsCRP ≥ 10 mg/L OR ESR ≥ 28
Exclusion criteria
* RA patients functional status class IV according to the ACR 1991 revised criteria * Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor * Previous exposure ever to an anti-TNF-a agent or any other immunomodulatory biologic agent (experimental or approved) * Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, or morphine) * Any therapy by intra-articular injections (e.g. corticosteroid, hyaluronan) required for treatment of arthritis within 4 weeks before randomization * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20) | 12 weeks | A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve ACR50 and ACR70 | 12 weeks | A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). |
| Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain | baseline, 12 weeks | The patient's assessment of pain was performed using 100 mm visual analog scale (VAS) ranging from 0 (no pain) to 100 (unbearable pain) after the question Please indicate with a vertical mark through the horizontal line the most pain you had from your rheumatoid arthritis over the last 24 hours. A negative change from baseline indicates improvement. |
| Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score. | baseline, 12 Weeks | The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from baseline indicates improvement. |
| Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP) | baseline, 12 weeks | The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28-CRP is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-CRP is calculated using the following formula: DAS28-4(crp) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP+1) + 0.014\*GH + 0.96. The calculation results in a DAS28-CRP score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6. A negative change from baseline indicates improvement. |
| Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR) | baseline, 12 weeks | The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), erythrocyte sedimentation rate (ESR), and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-ESR is calculated using the following formula: DAS28 = 0.56 \* sqrt(tender28) + 0.28 \* sqrt(swollen28) + 0.70 \* ln(ESR) + 0.014 \* GH. The calculation results in a DAS28-ESR score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6. A negative change from baseline indicates improvement. |
| Change From Baseline in Tender 68-joint Count | baseline, 12 weeks | The 68 joints assessed for tenderness included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0). A negative change from baseline indicates improvement. |
| Change From Baseline in Swollen 66-joint Count | baseline, 12 weeks | The 66 joints assessed for swelling included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0). A negative change in baseline indicates improvement. |
| Change From Baseline in Participant's Global Assessment of Disease Activity | baseline, 12 weeks | The patient's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question Considering all the ways rheumatoid arthritis affects you, please indicate with a vertical mark through the horizontal line how well you are doing today. A negative change from baseline indicates improvement. |
| Change From Baseline in Physician's Global Assessment of Disease Activity | baseline, 12 weeks | The physician's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question Considering all the ways rheumatoid arthritis affects your patient, how would you rate his or her current condition?. A negative change from baseline indicates improvement. |
| Change From Baseline in hsCRP | baseline, 12 weeks | Blood for this assessment was obtained to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement. |
| Change From Baseline in ESR | baseline, 12 weeks | Blood for this assessment was obtained to monitor disease activity and response to therapy. A negative change from baseline indicates improvement. |
| Percentage of Participants With European League Against Rheumatism (EULAR) Response | baseline, 12 weeks | EULAR response criteria are based on DAS28 status in combination with DAS28 improvements. The EULAR response criteria are as follows: present DAS28 \<3.2 with DAS28 improvement \>1.2 corresponds to 'good response'; present DAS28 \<3.2 with DAS28 improvement between 0.6 to 1.2, or present DAS28 between 3.2 to 5.1 with DAS28 improvement from 0.6 to \>1.2, or present DAS28 \>5.2 with DAS28 improvement \>1.2 correspond to 'moderate response; present DAS28 \<3.2 with DAS28 improvement \<0.6, or present DAS28 between 3.2 to 5.1 with DAS28 improvement \<0.6, or present DAS28 \>5.1 with DAS28 improvement \<0.6 to 1.2 correspond to 'no response'. |
Countries
Bulgaria, Canada, Hungary, Italy, Poland, Puerto Rico, Slovakia, United States
Participant flow
Recruitment details
Participants were randomized to one of the following 3 treatment groups in a 2:2:1 ratio: secukinumab 10 mg/kg i.v., secukinumab 150 mg s.c. or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 10 mg/kg i.v. Loading secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8 | 88 |
| Secukinumab 150 mg s.c. Loading secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8 | 89 |
| Placebo placebo at Weeks 0, 1, 2, 3, 4, 8 & 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16 | 44 |
| Total | 221 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind (Weeks 0 - 16) | Abnormal laboratory values | 1 | 0 | 0 |
| Double-blind (Weeks 0 - 16) | Adverse Event | 1 | 2 | 0 |
| Double-blind (Weeks 0 - 16) | Withdrawal by Subject | 0 | 2 | 0 |
| Follow-up (Weeks 52 - 60) | Abnormal laboratory value | 0 | 1 | 0 |
| Follow-up (Weeks 52 - 60) | Administrative problems | 1 | 0 | 0 |
| Follow-up (Weeks 52 - 60) | Adverse Event | 3 | 5 | 1 |
| Follow-up (Weeks 52 - 60) | Lack of Efficacy | 3 | 3 | 3 |
| Follow-up (Weeks 52 - 60) | Protocol deviation | 0 | 1 | 0 |
| Follow-up (Weeks 52 - 60) | Withdrawal by Subject | 1 | 5 | 4 |
| Open Label 150 mg s.c. (Weeks 16 - 52) | Abnormal laboratory values | 0 | 1 | 0 |
| Open Label 150 mg s.c. (Weeks 16 - 52) | Administrative problems | 1 | 0 | 0 |
| Open Label 150 mg s.c. (Weeks 16 - 52) | Adverse Event | 3 | 5 | 1 |
| Open Label 150 mg s.c. (Weeks 16 - 52) | Lack of Efficacy | 3 | 3 | 3 |
| Open Label 150 mg s.c. (Weeks 16 - 52) | Protocol deviation | 0 | 1 | 0 |
| Open Label 150 mg s.c. (Weeks 16 - 52) | Withdrawal by Subject | 1 | 3 | 4 |
Baseline characteristics
| Characteristic | Secukinumab 10 mg/kg i.v. Loading | Secukinumab 150 mg s.c. Loading | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 53.8 Years STANDARD_DEVIATION 11.81 | 54.5 Years STANDARD_DEVIATION 12.26 | 53.5 Years STANDARD_DEVIATION 9.33 | 54.0 Years STANDARD_DEVIATION 11.51 |
| Sex: Female, Male Female | 67 Participants | 72 Participants | 37 Participants | 176 Participants |
| Sex: Female, Male Male | 21 Participants | 17 Participants | 7 Participants | 45 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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 88 | 30 / 89 | 18 / 44 | 78 / 214 | 10 / 214 |
| serious Total, serious adverse events | 2 / 88 | 3 / 89 | 1 / 44 | 18 / 214 | 3 / 214 |
Outcome results
Primary
Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20)
A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).
Time frame: 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20) | 53.4 Percentage of participants |
| Secukinumab 150 mg s.c. Loading | Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20) | 44.9 Percentage of participants |
| Placebo | Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20) | 40.9 Percentage of participants |
Secondary
Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP)
The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28-CRP is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-CRP is calculated using the following formula: DAS28-4(crp) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP+1) + 0.014\*GH + 0.96. The calculation results in a DAS28-CRP score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6. A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Participants from the full analysis set (FAS), who had values at both baseline and week 12, were included in this analysis. The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP) | -1.67 score on a scale | Standard Error 0.119 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP) | -1.65 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP) | -1.21 score on a scale | Standard Error 0.166 |
Secondary
Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR)
The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), erythrocyte sedimentation rate (ESR), and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-ESR is calculated using the following formula: DAS28 = 0.56 \* sqrt(tender28) + 0.28 \* sqrt(swollen28) + 0.70 \* ln(ESR) + 0.014 \* GH. The calculation results in a DAS28-ESR score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6. A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Participants from the full analysis set (FAS), who had values at both baseline and week 12, were included in this analysis. The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR) | -1.98 score on a scale | Standard Error 0.126 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR) | -1.80 score on a scale | Standard Error 0.128 |
| Placebo | Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR) | -1.46 score on a scale | Standard Error 0.179 |
Secondary
Change From Baseline in ESR
Blood for this assessment was obtained to monitor disease activity and response to therapy. A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in ESR | -16.68 mm/hr | Standard Error 1.409 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in ESR | -12.43 mm/hr | Standard Error 1.425 |
| Placebo | Change From Baseline in ESR | -10.53 mm/hr | Standard Error 1.993 |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score.
The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from baseline indicates improvement.
Time frame: baseline, 12 Weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score. | -0.35 score on a scale | Standard Error 0.052 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score. | -0.28 score on a scale | Standard Error 0.053 |
| Placebo | Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score. | -0.17 score on a scale | Standard Error 0.074 |
Secondary
Change From Baseline in hsCRP
Blood for this assessment was obtained to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in hsCRP | -6.00 mg/L | Standard Error 0.938 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in hsCRP | -5.72 mg/L | Standard Error 0.946 |
| Placebo | Change From Baseline in hsCRP | -1.69 mg/L | Standard Error 1.336 |
Secondary
Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain
The patient's assessment of pain was performed using 100 mm visual analog scale (VAS) ranging from 0 (no pain) to 100 (unbearable pain) after the question Please indicate with a vertical mark through the horizontal line the most pain you had from your rheumatoid arthritis over the last 24 hours. A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain | -14.41 score on a scale | Standard Error 2.057 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain | -12.60 score on a scale | Standard Error 2.071 |
| Placebo | Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain | -6.66 score on a scale | Standard Error 2.902 |
Secondary
Change From Baseline in Participant's Global Assessment of Disease Activity
The patient's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question Considering all the ways rheumatoid arthritis affects you, please indicate with a vertical mark through the horizontal line how well you are doing today. A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in Participant's Global Assessment of Disease Activity | -18.58 score on a scale | Standard Error 2.042 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in Participant's Global Assessment of Disease Activity | -15.29 score on a scale | Standard Error 2.063 |
| Placebo | Change From Baseline in Participant's Global Assessment of Disease Activity | -9.93 score on a scale | Standard Error 2.884 |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity
The physician's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question Considering all the ways rheumatoid arthritis affects your patient, how would you rate his or her current condition?. A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in Physician's Global Assessment of Disease Activity | -27.05 score on a scale | Standard Error 1.925 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in Physician's Global Assessment of Disease Activity | -29.01 score on a scale | Standard Error 1.95 |
| Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity | 18.88 score on a scale | Standard Error 2.726 |
Secondary
Change From Baseline in Swollen 66-joint Count
The 66 joints assessed for swelling included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0). A negative change in baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in Swollen 66-joint Count | -9.49 Number of joints | Standard Error 0.607 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in Swollen 66-joint Count | -9.81 Number of joints | Standard Error 0.612 |
| Placebo | Change From Baseline in Swollen 66-joint Count | -7.88 Number of joints | Standard Error 0.863 |
Secondary
Change From Baseline in Tender 68-joint Count
The 68 joints assessed for tenderness included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0). A negative change from baseline indicates improvement.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Change From Baseline in Tender 68-joint Count | -10.31 Number of joints | Standard Error 1.093 |
| Secukinumab 150 mg s.c. Loading | Change From Baseline in Tender 68-joint Count | -11.99 Number of joints | Standard Error 1.099 |
| Placebo | Change From Baseline in Tender 68-joint Count | -9.50 Number of joints | Standard Error 1.549 |
Secondary
Percentage of Participants Who Achieve ACR50 and ACR70
A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).
Time frame: 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Percentage of Participants Who Achieve ACR50 and ACR70 | ACR50 | 20.5 Percentage of participants |
| Secukinumab 10 mg/kg i.v. Loading | Percentage of Participants Who Achieve ACR50 and ACR70 | ACR70 | 8.0 Percentage of participants |
| Secukinumab 150 mg s.c. Loading | Percentage of Participants Who Achieve ACR50 and ACR70 | ACR50 | 18.0 Percentage of participants |
| Secukinumab 150 mg s.c. Loading | Percentage of Participants Who Achieve ACR50 and ACR70 | ACR70 | 5.6 Percentage of participants |
| Placebo | Percentage of Participants Who Achieve ACR50 and ACR70 | ACR50 | 11.4 Percentage of participants |
| Placebo | Percentage of Participants Who Achieve ACR50 and ACR70 | ACR70 | 0.0 Percentage of participants |
Secondary
Percentage of Participants With European League Against Rheumatism (EULAR) Response
EULAR response criteria are based on DAS28 status in combination with DAS28 improvements. The EULAR response criteria are as follows: present DAS28 \<3.2 with DAS28 improvement \>1.2 corresponds to 'good response'; present DAS28 \<3.2 with DAS28 improvement between 0.6 to 1.2, or present DAS28 between 3.2 to 5.1 with DAS28 improvement from 0.6 to \>1.2, or present DAS28 \>5.2 with DAS28 improvement \>1.2 correspond to 'moderate response; present DAS28 \<3.2 with DAS28 improvement \<0.6, or present DAS28 between 3.2 to 5.1 with DAS28 improvement \<0.6, or present DAS28 \>5.1 with DAS28 improvement \<0.6 to 1.2 correspond to 'no response'.
Time frame: baseline, 12 weeks
Population: Full analysis set (FAS): The FAS included all participants who were randomized to study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Secukinumab 10 mg/kg i.v. Loading | Percentage of Participants With European League Against Rheumatism (EULAR) Response | Moderate response | 46.6 Percentage of participants |
| Secukinumab 10 mg/kg i.v. Loading | Percentage of Participants With European League Against Rheumatism (EULAR) Response | Good response | 28.4 Percentage of participants |
| Secukinumab 10 mg/kg i.v. Loading | Percentage of Participants With European League Against Rheumatism (EULAR) Response | No response | 25.0 Percentage of participants |
| Secukinumab 150 mg s.c. Loading | Percentage of Participants With European League Against Rheumatism (EULAR) Response | Moderate response | 44.9 Percentage of participants |
| Secukinumab 150 mg s.c. Loading | Percentage of Participants With European League Against Rheumatism (EULAR) Response | Good response | 27.0 Percentage of participants |
| Secukinumab 150 mg s.c. Loading | Percentage of Participants With European League Against Rheumatism (EULAR) Response | No response | 28.1 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response | Good response | 13.6 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response | No response | 34.1 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response | Moderate response | 52.3 Percentage of participants |