Rheumatoid Arthritis
Conditions
Keywords
Active Rheumatoid Arthritis, anti-interleukin-1beta monoclonal antibody, methotrexate
Brief summary
The 12-week core study was designed to evaluate risk-benefit of three subcutaneous dose regimens of ACZ885, added on to stable methotrexate (MTX) therapy (greater than or equal to 7.5 mg/week), compared to placebo in patients with active rheumatoid arthritis (RA). The study investigated the magnitude of effect as well as onset of effect for the different dose regimens. The primary objective of the extension studies was to assess long-term safety and tolerability of canakinumab (ACZ885) in patients with active RA. CACZ885A2201E1 evaluated this objective in patients who had participated in the core study (CACZ885A2201) and CACZ885A2201E2 did the same in patients who completed the first extension study.
Interventions
DRUGCanakinumab
DRUGPlacebo
Sponsors
Novartis
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
Other protocol-defined inclusion/
Exclusion criteria
may apply CORE STUDY Inclusion Criteria Core Study Inclusion Criteria At Screening 1. Cooperative male or non-pregnant, non-lactating female patients at least 18 years of age who signed an informed consent before the initiation of any study procedure. 2. Diagnosis of rheumatoid arthritis (RA) classified by American College of Rheumatology (ACR) 1987 revised criteria and with symptoms for at least 3 months before randomization. 3. Functional status class I, II or III classified according to the ACR 1991 revised criteria. 4. Patients treated with methotrexate (MTX) at the maximum tolerated (≤25 mg/week) and stable dose of ≥7.5 mg/week for at least 12 weeks before randomization. 5. Patients who had failed any disease-modifying antirheumatic drugs (DMARDs) (including biologic agents and any DMARD used in combination with MTX) were allowed. 6. For patients with previous treatment of biological therapy, the following wash-out periods were required before randomization: * 3 days for Kineret™ (anakinra) - with a terminal half-life of 4 to 6 hours (s.c. route). * 4 weeks for Enbrel® (etanercept) - with a terminal half-life of 102 ± 30 hours (s.c. route). * 8 weeks for Remicade® (infliximab) - with a terminal half-life of 8.0-9. 5 days (intravenous (i.v.) infusion). * 12 weeks for Humira® (adalimumab) - with a terminal half-life of 10-20 days (average 2 weeks) (subcutaneous (s.c.) route). * 12 weeks for Orencia® (abatacept) - with a terminal half-life of 13.1 (8-25) days (i.v. infusion). * 26 weeks for any other biologic - or 10 half-lives, whichever was longer. 7. Patients who took systemic corticosteroids had to be on a stable dose of ≤10 mg/d prednisone or equivalent for at least 4 weeks before randomization. 8. Patients who were regularly taking non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors or paracetamol/ acetaminophen as part of their RA therapy must have been on a stable dose for at least 4 weeks before randomization. Patients taking NSAIDs or COX-2 inhibitors or paracetamol/acetaminophen as needed within 2 weeks before randomization had to stop their medication at least 24 hours before an ACR visit (i.e. Visits 3, 7, 8, 10 and 12 \[End of Study\]). Patients taking folic acid supplementation had to be on stable dose for at least 4 weeks before randomization. 9. Patients with a history of immunization for Influenza (within past 12 months) and Pneumococcal vaccination (within 4 years) were included. If not already immunized, vaccination was completed when medically indicated (only during flu season for influenza) and such patients were included after approximately a 3 week window post-immunization to allow immunity to develop for vaccine. 10. Weight ≥45 kg and body mass index (BMI) \<34.0 11. Women of non-child-bearing potential, defined as all women physiologically not capable of becoming pregnant. Core Study Inclusion criteria At Baseline (Visit 3) 1. Disease activity criteria of ≥6 out of 28 tender joints and ≥6 out of 28 swollen joints. 2. One of the following also had to be present: 1. High-sensitive C-Reactive Protein (hsCRP) concentration ≥10 mg/L 2. Erythrocyte Sedimentation Rate (ESR) ≥28 mm/1st hr 3. a. + b. based on screening values. EXCLUSION 1. History of hypersensitivity to study drug or to molecules with similar structures. 2. Any therapy by intra-articular injections (e.g. corticosteroid) required for treatment of acute RA flare within 4 weeks before randomization. 3. Current use of DMARDs other than MTX. DMARDs included but were not limited to: biologic agents, thiolates (D-penicillamine, thiopronine), sulfasalazine, gold compounds, antimalarials, cyclosporine A, azathioprine, leflunomide, and alkylating agents such as cyclophosphamide. 4. If a patient had been discontinued from DMARDs, the patient should have been off the agent for at least 4 weeks, except leflunomide which was 8 weeks. 5. Patients with evidence of active pulmonary disease (e.g. tuberculosis, fungal diseases). 6. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing. 7. Who had a live vaccination within 12 weeks before randomization, or were planning to have one during the study and were not willing/able to postpone until study completion. 8. a) With bacterial, fungal or viral infections at the time of enrollment, including patients with evidence of human immunodeficiency virus (HIV) infection, hepatitis B and hepatitis C infection. b) History of a positive purified protein derivative (PPD) of tuberculin skin test without a follow-up of a negative chest X-ray. c) Patients requiring administration of antibiotics against latent tuberculosis, e.g. isoniazide. 9. Underlying metabolic, hematologic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromised the patient and/or placed the patient at unacceptable risk for participation in an immunomodulatory therapy. In particular, clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty's syndrome. 10. With significant medical problems, including but not limited to the following: uncontrolled hypertension (≥160/95 mmHg), congestive heart failure, type-I-diabetes(well controlled type-II-diabetes was allowed even when requiring insulin), thyroid disease (unless the patient was taking a stable dose of thyroid hormone for at least 12 weeks before randomization). 11. Other rheumatic diseases that could confound the evaluation of efficacy, including but not limited to primary fibromyalgia, ankylosing spondylitis, Lyme disease, adult juvenile RA, systemic lupus erythematosus, gout and pseudo gout, vasculitis, psoriatic arthritis, reactive arthritis, primary Sjoegren's Syndrome, and Behcet's Syndrome. 12. Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol. 13. History of malignancy of any organ system, treated or untreated, within the past 5 years (with the exception of adequately treated basal cell carcinoma or squamous-cell carcinoma of the skin, carcinoma in situ of the cervix, colon polyps with non-invasive malignancy that have been removed). 14. Use of any investigational drug other than RA therapy and/or devices at the time of randomization, or within 30 days or 5 half- lives of randomization, whichever was longer. STUDY EXTENSIONS Extension Studies Inclusion Criteria: 1. Patients who completed the core CACZ885A2201 study may enter the first extension study upon signing informed consent. A patient is defined as completing the study if he/she completed the core CACZ885A2201 study up to and including Visit 12. 2. Patients who completed the first extension study, may enter the second. Extension Studies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12 | Baseline and Week 12 | Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Details on each of these components are provided in Outcome Measures 10-16. Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders. |
| Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124 | Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR20 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders. |
| Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124 | Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders. |
| Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124 | Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR70 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders. |
| Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Baseline and Weeks 24, 72 and 112 | The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) in mg/L; * Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Tender 28-joint Count | Baseline and Weeks 2, 4, 8 and 12 | The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate. |
| Change From Baseline in Patient's Pain Intensity | Baseline and Weeks 2, 4, 8 and 12 | The patient's assessment of pain was performed using a 100 mm visual analog scale (VAS) ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate. |
| Change From Baseline in Patient's Global Assessment of Disease Activity | Baseline and Weeks 2, 4, 8 and 12 | The patient's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100), after the question Considering all the ways your arthritis affects you, draw a line on the scale for how well you are doing. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate. |
| Change From Baseline in Physician's Global Assessment of Disease Activity | Baseline and Weeks 2, 4, 8 and 12 | The physician's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment of disease activity when performing their own assessment on that patient. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate. |
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Baseline and Weeks 2, 4, 8 and 12 | The patient health assessment questionnaire (HAQ) was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from Baseline score indicates improvement in disability status. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate. |
| Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Baseline and Weeks 2, 4, 8 and 12 | HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate. |
| Change From Baseline in Disease Activity Score (DAS) 28 | Baseline and Weeks 2, 4, 8 and 12 | The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) in mg/L; * Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. 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. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline DAS28 value as a covariate. |
| Change From Baseline in Erythrocyte Sedimentation Rate | Baseline and Weeks 2, 4, 8 and 12 | Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. A negative change from Baseline score indicates improvement. |
| Change From Baseline in Rheumatoid Factor Concentration | Baseline and Weeks 4, 8 and 12 | Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) that is an indicator of inflammation and rheumatoid arthritis. |
| Change From Baseline in Short Form 36 Health Survey (SF-36) | Baseline and Weeks 2, 4, 8 and 12 | The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life. |
| Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Baseline and Weeks 2, 4 and 8 | Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders. |
| Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | Baseline and End of Study (up to 124 weeks) | To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, patients were categorized as follows: 1. Did not attain an ACR20 response; 2. Attained a 20% but not a 50% response; 3. Attained a 50% but not a 70% response; 4. Attained a 70% or greater response. A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire \[HAQ\] score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). |
| Change From Baseline in Swollen 28-joint Count During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. | The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). |
| Change From Baseline in Tender 28-joint Count During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. | The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). |
| Change From Baseline in Patient's Pain Intensity During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. | The patient's assessment of pain was performed using a 100 mm visual analog scale (VAS) ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity. |
| Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. | The patient's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100), after the question Considering all the ways your arthritis affects you, draw a line on the scale for how well you are doing. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. |
| Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. | The physician's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment of disease activity when performing their own assessment on that patient. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. |
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. | The patient health assessment questionnaire (HAQ) was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from Baseline score indicates improvement in disability status. |
| Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. | HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. |
| Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Baseline and Weeks 24, 36, 48, 60, 72 and 88. | Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. A negative change from Baseline score indicates improvement. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Baseline and Weeks 2, 4, 8 and 12 | The fatigue subscale of the FACIT is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants respond to each item on a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT Fatigue subscale scores range from 0 to 52, where higher scores represent less fatigue. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline FACIT-F value as a covariate. |
| Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Baseline and Weeks 2, 4, 8 and 12 | Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered ACR20 non-responders if they failed the ACR20 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders. |
| Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Baseline and Weeks 2, 4, 8 and 12 | Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered ACR70 non-responders if they failed the ACR70 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders. |
| Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | Baseline and Week 12 | To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, participants were categorized as follows: 1. Did not attain an ACR20 response; 2. Attained a 20% but not a 50% response; 3. Attained a 50% but not a 70% response; 4. Attained a 70% or greater response. A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire \[HAQ\] score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). |
| Change From Baseline in Swollen 28-joint Count | Baseline and Weeks 2, 4, 8 and 12 | The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate. |
Countries
Austria, Belgium, Canada, Germany, Spain, United States
Participant flow
Recruitment details
277 patients were randomized in core (CACZ885A2201): 71 were assigned to ACZ885 600 mg intravenous(iv) + 300 mg subcutaneous each 2 weeks(sc q2wk), 66 to ACZ885 300 mg sc q2wk, 69 to ACZ885 150 mg sc q4wk, 71 to placebo. 3 were randomized but not treated. All other 274 (98.9%) were treated and had post-baseline efficacy data.
Pre-assignment details
Enrollment in core & CACZ885A2201E2 was determined by how many entered first extension study. Study protocols did not mandate that patients continue treatment in the extension phase and furthermore the reason for not continuing from the Core to the Extension phase was not capture. A total of 6.6% completed extensions.
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks. | 71 |
| Canakinumab 300 mg q2wk Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. | 64 |
| Canakinumab 150 mg q4wk Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. | 69 |
| Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. | 70 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Core Study | Abnormal Laboratory Values | 0 | 1 | 0 | 0 |
| Core Study | Administrative Problems | 1 | 0 | 1 | 0 |
| Core Study | Adverse Event | 5 | 3 | 1 | 1 |
| Core Study | Lack of Efficacy | 1 | 3 | 0 | 4 |
| Core Study | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Core Study | Protocol Violation | 0 | 0 | 2 | 0 |
| Core Study | Withdrawal by Subject | 1 | 0 | 0 | 2 |
| Extension Phase | Administrative Problems | 0 | 69 | 32 | 35 |
| Extension Phase | Adverse Event | 0 | 9 | 5 | 4 |
| Extension Phase | Death | 0 | 0 | 0 | 1 |
| Extension Phase | Lack of Efficacy | 0 | 16 | 14 | 11 |
| Extension Phase | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Extension Phase | Protocol Violation | 0 | 1 | 1 | 0 |
| Extension Phase | Withdrawal by Subject | 0 | 5 | 3 | 4 |
Baseline characteristics
| Characteristic | Canakinumab 600 mg IV + 300 mg q2wk | Canakinumab 300 mg q2wk | Canakinumab 150 mg q4wk | Placebo | Total |
|---|---|---|---|---|---|
| Age, Customized ≥18 - <41 years | 5 participants | 5 participants | 7 participants | 7 participants | 24 participants |
| Age, Customized ≥41 - <65 years | NA participants | 31 participants | 43 participants | 43 participants | 167 participants |
| Age, Customized ≥65 - <75 years | 11 participants | 25 participants | 12 participants | 12 participants | 49 participants |
| Age, Customized ≥75 years | NA participants | 10 participants | 3 participants | 4 participants | 22 participants |
| Gender Female | 0 participants | 94 participants | 47 participants | 44 participants | 185 participants |
| Gender Male | 0 participants | 16 participants | 12 participants | 14 participants | 42 participants |
| Sex: Female, Male Female | 60 Participants | 57 Participants | 56 Participants | 52 Participants | 225 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 13 Participants | 18 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 71 | 38 / 64 | 39 / 69 | 40 / 70 |
| serious Total, serious adverse events | 11 / 71 | 16 / 64 | 12 / 69 | 16 / 70 |
Outcome results
Primary
Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase
The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) in mg/L; * Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. 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
Time frame: Baseline and Weeks 24, 72 and 112
Population: The Extension Study intent-to-treat (ITT) population consisted of all patients who entered the extension study and who received at least one dose of study drug in the extension studies. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 72 [N=63, 31, 26] | -2.18 scores on a scale | Standard Deviation 1.302 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | End of Study Visit [N=100, 52, 49} | -1.83 scores on a scale | Standard Deviation 1.434 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 112 [N=13, 8, 6] | -2.00 scores on a scale | Standard Deviation 1.11 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 24 [N=103, 56, 54] | -1.60 scores on a scale | Standard Deviation 1.171 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 112 [N=13, 8, 6] | -2.73 scores on a scale | Standard Deviation 1.252 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | End of Study Visit [N=100, 52, 49} | -1.79 scores on a scale | Standard Deviation 1.551 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 72 [N=63, 31, 26] | -2.58 scores on a scale | Standard Deviation 1.232 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 24 [N=103, 56, 54] | -1.82 scores on a scale | Standard Deviation 1.333 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | End of Study Visit [N=100, 52, 49} | -1.86 scores on a scale | Standard Deviation 1.621 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 24 [N=103, 56, 54] | -1.93 scores on a scale | Standard Deviation 1.474 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 112 [N=13, 8, 6] | -2.59 scores on a scale | Standard Deviation 1.916 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase | Week 72 [N=63, 31, 26] | -2.21 scores on a scale | Standard Deviation 1.132 |
Primary
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase
Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR20 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Population: The Extension Study intent-to-treat (ITT) population consisted of all patients who entered the extension study and who received at least one dose of study drug in the extension studies. The number of patients in the analysis at each time point (N) includes those with ACR20 evaluation data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 24 [N=105, 57, 56] | 52.4 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 57.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 48 [N=95, 43, 47] | 66.3 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 60.9 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 62.1 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 88 [N=43, 25, 23] | 67.4 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 100 [N=21, 12, 14] | 81.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 76.9 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 100.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 53, 54] | 51.5 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 100.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 24 [N=105, 57, 56] | 64.9 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 88 [N=43, 25, 23] | 72.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 76.5 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 66.7 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 53, 54] | 54.7 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 75.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 48 [N=95, 43, 47] | 81.4 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 100 [N=21, 12, 14] | 75.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 75.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 66.7 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 73.8 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 74.1 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 88 [N=43, 25, 23] | 82.6 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 100.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 100 [N=21, 12, 14] | 91.7 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 24 [N=105, 57, 56] | 66.1 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 53, 54] | 61.1 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 63.3 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase | Week 48 [N=95, 43, 47] | 72.3 percentage of participants |
Primary
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Details on each of these components are provided in Outcome Measures 10-16. Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Time frame: Baseline and Week 12
Population: The intent-to-treat (ITT) population consisted of all patients as randomized that received at least one dose of study drug and had at least one post-baseline efficacy assessment. The number of patients in the analysis includes those with ACR50 evaluation. Last observation carried forward was applied for all the component variables.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12 | 9.9 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12 | 23.4 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12 | 26.5 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12 | 11.4 percentage of participants |
Primary
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Population: The Extension Study intent-to-treat (ITT) population consisted of all patients who entered the extension study and who received at least one dose of study drug in the extension studies. The number of patients in the analysis at each time point (N) includes those with ACR50 evaluation data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 24 [N=106, 57, 56] | 18.9 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 24.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 48 [N=95, 43, 47] | 34.7 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 34.5 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 37.9 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 88 [N=43, 25, 23] | 39.5 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 100 [N=21, 13, 14] | 47.6 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 23.1 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 50.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 53, 54] | 23.3 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 100.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 24 [N=106, 57, 56] | 29.8 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 88 [N=43, 25, 23] | 44.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 58.8 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 31.3 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 53, 54] | 35.8 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 62.5 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 48 [N=95, 43, 47] | 48.8 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 100 [N=21, 13, 14] | 30.8 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 42.5 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 66.7 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 42.9 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 48.1 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 88 [N=43, 25, 23] | 52.2 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 100.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 100 [N=21, 13, 14] | 57.1 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 24 [N=106, 57, 56] | 37.5 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 53, 54] | 35.2 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 32.7 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase | Week 48 [N=95, 43, 47] | 34.0 percentage of participants |
Primary
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase
Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR70 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Population: The Extension Study intent-to-treat (ITT) population consisted of all patients who entered the extension study and who received at least one dose of study drug in the extension studies. The number of patients in the analysis at each time point (N) includes those with ACR70 evaluation data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 24 [N=106, 57, 56] | 5.7 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 7.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 48 [N=96, 43, 47] | 10.4 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 16.1 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 15.2 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 88 [N=44, 25, 23] | 15.9 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 100 [N=21, 14, 14] | 14.3 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 7.7 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 50.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 54, 54] | 13.6 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 100.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 24 [N=106, 57, 56] | 10.5 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 88 [N=44, 25, 23] | 16.0 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 20.6 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 4.2 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 54, 54] | 16.7 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 37.5 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 48 [N=96, 43, 47] | 9.3 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 100 [N=21, 14, 14] | 21.4 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 17.5 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 112 [N=13, 8, 6] | 33.3 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 60 [N=87, 40, 42] | 19.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 72 [N=66, 34, 27] | 14.8 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 88 [N=44, 25, 23] | 17.4 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 124 [N=2, 1, 1] | 0.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 100 [N=21, 14, 14] | 28.6 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 24 [N=106, 57, 56] | 14.3 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | End of Study Visit [N=103, 54, 54] | 13.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 36 [N=100, 48, 49] | 12.2 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase | Week 48 [N=96, 43, 47] | 6.4 percentage of participants |
Secondary
Change From Baseline in Disease Activity Score (DAS) 28
The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) in mg/L; * Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. 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. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline DAS28 value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 2 [N=69, 64, 66, 70] | -0.7 scores on a scale | Standard Error 0.11 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 4 [N=71, 64, 68, 70] | -0.9 scores on a scale | Standard Error 0.13 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 8 [N=71, 64, 68, 70] | -1.1 scores on a scale | Standard Error 0.14 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 12 [N=71, 64, 68, 70] | -1.2 scores on a scale | Standard Error 0.15 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 4 [N=71, 64, 68, 70] | -1.0 scores on a scale | Standard Error 0.13 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 8 [N=71, 64, 68, 70] | -1.2 scores on a scale | Standard Error 0.15 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 12 [N=71, 64, 68, 70] | -1.3 scores on a scale | Standard Error 0.16 |
| Canakinumab 300 mg q2wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 2 [N=69, 64, 66, 70] | -0.7 scores on a scale | Standard Error 0.11 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 8 [N=71, 64, 68, 70] | -1.2 scores on a scale | Standard Error 0.14 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 4 [N=71, 64, 68, 70] | -1.1 scores on a scale | Standard Error 0.13 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 12 [N=71, 64, 68, 70] | -1.5 scores on a scale | Standard Error 0.15 |
| Canakinumab 150 mg q4wk | Change From Baseline in Disease Activity Score (DAS) 28 | Week 2 [N=69, 64, 66, 70] | -0.8 scores on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Disease Activity Score (DAS) 28 | Week 12 [N=71, 64, 68, 70] | -0.9 scores on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in Disease Activity Score (DAS) 28 | Week 4 [N=71, 64, 68, 70] | -0.7 scores on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in Disease Activity Score (DAS) 28 | Week 2 [N=69, 64, 66, 70] | -0.5 scores on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Disease Activity Score (DAS) 28 | Week 8 [N=71, 64, 68, 70] | -0.8 scores on a scale | Standard Error 0.14 |
Secondary
Change From Baseline in Erythrocyte Sedimentation Rate
Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. A negative change from Baseline score indicates improvement.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 2 [N=68, 64, 67, 69] | -9.0 mm/hr | Standard Deviation 12.85 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 4 [N=71, 64, 69, 70] | -9.2 mm/hr | Standard Deviation 15.11 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 8 [N=71, 64, 69, 70] | -11.3 mm/hr | Standard Deviation 16.28 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 12 [N=71, 64, 69, 70] | -11.2 mm/hr | Standard Deviation 18.2 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 4 [N=71, 64, 69, 70] | -9.6 mm/hr | Standard Deviation 17.43 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 8 [N=71, 64, 69, 70] | -12.3 mm/hr | Standard Deviation 16.02 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 12 [N=71, 64, 69, 70] | -11.1 mm/hr | Standard Deviation 18.12 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 2 [N=68, 64, 67, 69] | -8.2 mm/hr | Standard Deviation 15.97 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 8 [N=71, 64, 69, 70] | -12.8 mm/hr | Standard Deviation 13.89 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 4 [N=71, 64, 69, 70] | -11.8 mm/hr | Standard Deviation 14.71 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 12 [N=71, 64, 69, 70] | -15.1 mm/hr | Standard Deviation 14.96 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate | Week 2 [N=68, 64, 67, 69] | -9.0 mm/hr | Standard Deviation 12.43 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Week 12 [N=71, 64, 69, 70] | -4.1 mm/hr | Standard Deviation 16.73 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Week 4 [N=71, 64, 69, 70] | -2.6 mm/hr | Standard Deviation 12.94 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Week 2 [N=68, 64, 67, 69] | -2.9 mm/hr | Standard Deviation 11.62 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Week 8 [N=71, 64, 69, 70] | -4.4 mm/hr | Standard Deviation 15.65 |
Secondary
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study
Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. A negative change from Baseline score indicates improvement.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72 and 88.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 36 [N=95, 46, 48] | -14.5 mm/hr | Standard Deviation 18.99 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 72 [N=64, 34, 26] | -18.6 mm/hr | Standard Deviation 17.83 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 60 [N=85, 39, 43] | -17.2 mm/hr | Standard Deviation 19.07 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 24 [N=105, 58, 54] | -14.9 mm/hr | Standard Deviation 17.31 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | End of Study Visit [N=98, 55, 55] | -14.9 mm/hr | Standard Deviation 18.09 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 88 [N=42, 24, 23] | -19.7 mm/hr | Standard Deviation 17.46 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 48 [N=91, 42, 47] | -15.6 mm/hr | Standard Deviation 20.13 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 60 [N=85, 39, 43] | -15.8 mm/hr | Standard Deviation 19.08 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 24 [N=105, 58, 54] | -18.3 mm/hr | Standard Deviation 14.96 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 36 [N=95, 46, 48] | -13.6 mm/hr | Standard Deviation 19.09 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 48 [N=91, 42, 47] | -16.6 mm/hr | Standard Deviation 13.44 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 72 [N=64, 34, 26] | -15.3 mm/hr | Standard Deviation 16.39 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 88 [N=42, 24, 23] | -13.5 mm/hr | Standard Deviation 16.38 |
| Canakinumab 300 mg q2wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | End of Study Visit [N=98, 55, 55] | -14.0 mm/hr | Standard Deviation 17.51 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 72 [N=64, 34, 26] | -14.1 mm/hr | Standard Deviation 23.1 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 36 [N=95, 46, 48] | -11.3 mm/hr | Standard Deviation 25.94 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | End of Study Visit [N=98, 55, 55] | -15.9 mm/hr | Standard Deviation 18.1 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 88 [N=42, 24, 23] | -13.3 mm/hr | Standard Deviation 20.89 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 60 [N=85, 39, 43] | -16.7 mm/hr | Standard Deviation 19.09 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 48 [N=91, 42, 47] | -17.0 mm/hr | Standard Deviation 18.81 |
| Canakinumab 150 mg q4wk | Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study | Week 24 [N=105, 58, 54] | -16.8 mm/hr | Standard Deviation 17.1 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F)
The fatigue subscale of the FACIT is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants respond to each item on a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT Fatigue subscale scores range from 0 to 52, where higher scores represent less fatigue. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline FACIT-F value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 2 [N=62, 63, 63, 64] | 2.5 scores on a scale | Standard Error 0.9 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 4 [N=66, 64, 66, 67] | 3.8 scores on a scale | Standard Error 0.99 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 12 [N=67, 64, 66, 67] | 4.9 scores on a scale | Standard Error 1.14 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 8 [N=67, 64, 66, 67] | 4.2 scores on a scale | Standard Error 1.13 |
| Canakinumab 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 2 [N=62, 63, 63, 64] | 1.6 scores on a scale | Standard Error 0.87 |
| Canakinumab 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 12 [N=67, 64, 66, 67] | 3.8 scores on a scale | Standard Error 1.15 |
| Canakinumab 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 4 [N=66, 64, 66, 67] | 3.3 scores on a scale | Standard Error 0.99 |
| Canakinumab 300 mg q2wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 8 [N=67, 64, 66, 67] | 4.0 scores on a scale | Standard Error 1.15 |
| Canakinumab 150 mg q4wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 2 [N=62, 63, 63, 64] | 3.7 scores on a scale | Standard Error 0.89 |
| Canakinumab 150 mg q4wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 12 [N=67, 64, 66, 67] | 5.7 scores on a scale | Standard Error 1.14 |
| Canakinumab 150 mg q4wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 8 [N=67, 64, 66, 67] | 4.6 scores on a scale | Standard Error 1.13 |
| Canakinumab 150 mg q4wk | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 4 [N=66, 64, 66, 67] | 4.9 scores on a scale | Standard Error 0.98 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 12 [N=67, 64, 66, 67] | 1.4 scores on a scale | Standard Error 1.16 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 2 [N=62, 63, 63, 64] | 2.5 scores on a scale | Standard Error 0.89 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 8 [N=67, 64, 66, 67] | 2.1 scores on a scale | Standard Error 1.15 |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) | Week 4 [N=66, 64, 66, 67] | 2.1 scores on a scale | Standard Error 1 |
Secondary
Change From Baseline in Health Assessment Questionnaire (HAQ) Score
The patient health assessment questionnaire (HAQ) was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from Baseline score indicates improvement in disability status. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 2 [N=70, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.04 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 4 [N=71, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.05 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 8 [N=71, 64, 69, 70] | -0.2 scores on a scale | Standard Error 0.06 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 12 [N=71, 64, 69, 70] | -0.2 scores on a scale | Standard Error 0.06 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 12 [N=71, 64, 69, 70] | -0.2 scores on a scale | Standard Error 0.06 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 8 [N=71, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.06 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 4 [N=71, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.05 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 2 [N=70, 64, 69, 70] | 0.0 scores on a scale | Standard Error 0.05 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 8 [N=71, 64, 69, 70] | -0.2 scores on a scale | Standard Error 0.06 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 12 [N=71, 64, 69, 70] | -0.2 scores on a scale | Standard Error 0.06 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 4 [N=71, 64, 69, 70] | -0.2 scores on a scale | Standard Error 0.05 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 2 [N=70, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 12 [N=71, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 2 [N=70, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 4 [N=71, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Week 8 [N=71, 64, 69, 70] | -0.1 scores on a scale | Standard Error 0.06 |
Secondary
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study
The patient health assessment questionnaire (HAQ) was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from Baseline score indicates improvement in disability status.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 124 [N=2, 1, 1] | -0.938 scores on a scale | Standard Deviation 0.6187 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 24 [N=106, 58, 56] | -0.241 scores on a scale | Standard Deviation 0.543 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 72 [N=65, 34, 27] | -0.398 scores on a scale | Standard Deviation 0.6047 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | End of Study Visit [N=101, 54, 54] | -0.260 scores on a scale | Standard Deviation 0.6051 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 36 [N=99, 49, 48] | -0.266 scores on a scale | Standard Deviation 0.5418 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 88 [N=44, 25, 23] | -0.472 scores on a scale | Standard Deviation 0.5985 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 112 [N=13, 8, 6] | -0.538 scores on a scale | Standard Deviation 0.541 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 60 [N=86, 40, 42] | -0.347 scores on a scale | Standard Deviation 0.5552 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 100 [N=21, 13, 14] | -0.613 scores on a scale | Standard Deviation 0.5504 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 48 [N=96, 44, 47] | -0.322 scores on a scale | Standard Deviation 0.5446 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 100 [N=21, 13, 14] | -0.298 scores on a scale | Standard Deviation 0.4692 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 112 [N=13, 8, 6] | -0.406 scores on a scale | Standard Deviation 0.664 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 48 [N=96, 44, 47] | -0.324 scores on a scale | Standard Deviation 0.4988 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 124 [N=2, 1, 1] | -0.625 scores on a scale | — |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 24 [N=106, 58, 56] | -0.304 scores on a scale | Standard Deviation 0.4895 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | End of Study Visit [N=101, 54, 54] | -0.322 scores on a scale | Standard Deviation 0.5724 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 60 [N=86, 40, 42] | -0.419 scores on a scale | Standard Deviation 0.5819 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 72 [N=65, 34, 27] | -0.441 scores on a scale | Standard Deviation 0.5849 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 88 [N=44, 25, 23] | -0.440 scores on a scale | Standard Deviation 0.5218 |
| Canakinumab 300 mg q2wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 36 [N=99, 49, 48] | -0.347 scores on a scale | Standard Deviation 0.5066 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | End of Study Visit [N=101, 54, 54] | -0.291 scores on a scale | Standard Deviation 0.6259 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 24 [N=106, 58, 56] | -0.239 scores on a scale | Standard Deviation 0.5142 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 48 [N=96, 44, 47] | -0.293 scores on a scale | Standard Deviation 0.5375 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 60 [N=86, 40, 42] | -0.425 scores on a scale | Standard Deviation 0.6047 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 72 [N=65, 34, 27] | -0.449 scores on a scale | Standard Deviation 0.6338 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 88 [N=44, 25, 23] | -0.451 scores on a scale | Standard Deviation 0.5823 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 100 [N=21, 13, 14] | -0.563 scores on a scale | Standard Deviation 0.7448 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 112 [N=13, 8, 6] | -0.542 scores on a scale | Standard Deviation 0.71 |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 124 [N=2, 1, 1] | -1.250 scores on a scale | — |
| Canakinumab 150 mg q4wk | Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study | Week 36 [N=99, 49, 48] | -0.302 scores on a scale | Standard Deviation 0.5511 |
Secondary
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels
HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 2 [N=69, 64, 67, 70] | -5.6 mg/L | Standard Error 1.72 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 4 [N=71, 64, 69, 70] | -5.2 mg/L | Standard Error 1.69 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 8 [N=71, 64, 69, 70] | -4.3 mg/L | Standard Error 1.72 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 12 [N=71, 64, 69, 70] | -5.6 mg/L | Standard Error 1.89 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 4 [N=71, 64, 69, 70] | -7.4 mg/L | Standard Error 1.78 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 8 [N=71, 64, 69, 70] | -6.9 mg/L | Standard Error 1.82 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 12 [N=71, 64, 69, 70] | -3.4 mg/L | Standard Error 1.99 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 2 [N=69, 64, 67, 70] | -5.8 mg/L | Standard Error 1.79 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 8 [N=71, 64, 69, 70] | -3.5 mg/L | Standard Error 1.75 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 4 [N=71, 64, 69, 70] | -6.5 mg/L | Standard Error 1.72 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 12 [N=71, 64, 69, 70] | -8.0 mg/L | Standard Error 1.92 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 2 [N=69, 64, 67, 70] | -4.7 mg/L | Standard Error 1.75 |
| Placebo | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 12 [N=71, 64, 69, 70] | -0.7 mg/L | Standard Error 1.94 |
| Placebo | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 4 [N=71, 64, 69, 70] | -1.7 mg/L | Standard Error 1.73 |
| Placebo | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 2 [N=69, 64, 67, 70] | -1.7 mg/L | Standard Error 1.74 |
| Placebo | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels | Week 8 [N=71, 64, 69, 70] | 0.0 mg/L | Standard Error 1.77 |
Secondary
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study
HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 24 [N=106, 58, 55] | -4.82 mg/L | Standard Deviation 17.914 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 36 [N=97, 49, 50] | -7.76 mg/L | Standard Deviation 16.771 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 48 [N=95, 44, 47] | -5.61 mg/L | Standard Deviation 22.335 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 60 [N=88, 40, 43] | -6.93 mg/L | Standard Deviation 21.16 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 72 [N=63, 33, 26] | -9.02 mg/L | Standard Deviation 18.067 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 88 [N=44, 24, 22] | -8.45 mg/L | Standard Deviation 19.06 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 100 [N=21, 14, 12] | -7.29 mg/L | Standard Deviation 12.85 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 112 [N=13, 9, 6] | -5.75 mg/L | Standard Deviation 10.438 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 124 [N=2, 1, 1] | 4.95 mg/L | Standard Deviation 13.364 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | End of Study Visit [N=101, 57, 52] | -7.01 mg/L | Standard Deviation 17.934 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 124 [N=2, 1, 1] | -22.70 mg/L | — |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 24 [N=106, 58, 55] | -6.45 mg/L | Standard Deviation 14.556 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 88 [N=44, 24, 22] | -7.31 mg/L | Standard Deviation 13.035 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 72 [N=63, 33, 26] | -5.29 mg/L | Standard Deviation 15.219 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 36 [N=97, 49, 50] | -4.57 mg/L | Standard Deviation 14.393 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | End of Study Visit [N=101, 57, 52] | -2.94 mg/L | Standard Deviation 15.735 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 112 [N=13, 9, 6] | -1.80 mg/L | Standard Deviation 18.838 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 48 [N=95, 44, 47] | -4.63 mg/L | Standard Deviation 13.521 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 100 [N=21, 14, 12] | -2.74 mg/L | Standard Deviation 17.273 |
| Canakinumab 300 mg q2wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 60 [N=88, 40, 43] | 0.49 mg/L | Standard Deviation 47.139 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 112 [N=13, 9, 6] | -19.33 mg/L | Standard Deviation 35.567 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 60 [N=88, 40, 43] | -7.04 mg/L | Standard Deviation 18.638 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 72 [N=63, 33, 26] | -7.70 mg/L | Standard Deviation 18.221 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 88 [N=44, 24, 22] | -7.65 mg/L | Standard Deviation 18.098 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 124 [N=2, 1, 1] | 0.20 mg/L | — |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 100 [N=21, 14, 12] | -10.74 mg/L | Standard Deviation 24.539 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 24 [N=106, 58, 55] | -9.59 mg/L | Standard Deviation 18.388 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | End of Study Visit [N=101, 57, 52] | -9.74 mg/L | Standard Deviation 20.766 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 36 [N=97, 49, 50] | 0.50 mg/L | Standard Deviation 71.61 |
| Canakinumab 150 mg q4wk | Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study | Week 48 [N=95, 44, 47] | -11.04 mg/L | Standard Deviation 20.261 |
Secondary
Change From Baseline in Patient's Global Assessment of Disease Activity
The patient's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100), after the question Considering all the ways your arthritis affects you, draw a line on the scale for how well you are doing. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 12 [N= 71, 64, 68, 70] | -14.5 scores on a scale | Standard Error 2.61 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 4 [N= 71, 64, 68, 70] | -9.4 scores on a scale | Standard Error 2.28 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 70] | -6.4 scores on a scale | Standard Error 2.12 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 8 [N= 71, 64, 68, 70] | -13.9 scores on a scale | Standard Error 2.63 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 4 [N= 71, 64, 68, 70] | -11.2 scores on a scale | Standard Error 2.39 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 8 [N= 71, 64, 68, 70] | -15.7 scores on a scale | Standard Error 2.76 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 70] | -7.5 scores on a scale | Standard Error 2.21 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 12 [N= 71, 64, 68, 70] | -17.5 scores on a scale | Standard Error 2.74 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 70] | -7.9 scores on a scale | Standard Error 2.15 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 4 [N= 71, 64, 68, 70] | -12.8 scores on a scale | Standard Error 2.33 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 8 [N= 71, 64, 68, 70] | -13.8 scores on a scale | Standard Error 2.68 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 12 [N= 71, 64, 68, 70] | -17.6 scores on a scale | Standard Error 2.66 |
| Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 4 [N= 71, 64, 68, 70] | -6.1 scores on a scale | Standard Error 2.33 |
| Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 70] | -5.0 scores on a scale | Standard Error 2.15 |
| Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 12 [N= 71, 64, 68, 70] | -10.1 scores on a scale | Standard Error 2.66 |
| Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity | Week 8 [N= 71, 64, 68, 70] | -6.9 scores on a scale | Standard Error 2.68 |
Secondary
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study
The patient's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100), after the question Considering all the ways your arthritis affects you, draw a line on the scale for how well you are doing. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 24 [N=105, 57, 56] | -23.2 scores on a scale | Standard Deviation 26.12 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 36 [N=100, 48, 48] | -22.5 scores on a scale | Standard Deviation 28.61 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 48 [N=96, 43, 47] | -25.8 scores on a scale | Standard Deviation 27.92 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 60 [N=87, 40, 42] | -27.7 scores on a scale | Standard Deviation 29.08 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 72 [N=66, 33, 27] | -28.6 scores on a scale | Standard Deviation 24.54 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 88 [N=43, 25, 23] | -28.4 scores on a scale | Standard Deviation 27.77 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 100 [N=21, 13, 14] | -34.1 scores on a scale | Standard Deviation 20.69 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 112 [N=13, 8, 6] | -29.9 scores on a scale | Standard Deviation 23.05 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 124 [N=2, 1, 1] | -59.5 scores on a scale | Standard Deviation 20.51 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | End of Study Visit [N=103, 52, 54] | -20.4 scores on a scale | Standard Deviation 27.93 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 124 [N=2, 1, 1] | -20.0 scores on a scale | — |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 24 [N=105, 57, 56] | -21.9 scores on a scale | Standard Deviation 23.21 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 88 [N=43, 25, 23] | -30.9 scores on a scale | Standard Deviation 25.59 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 72 [N=66, 33, 27] | -32.1 scores on a scale | Standard Deviation 26.56 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 36 [N=100, 48, 48] | -23.8 scores on a scale | Standard Deviation 23.11 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | End of Study Visit [N=103, 52, 54] | -19.7 scores on a scale | Standard Deviation 26.29 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 112 [N=13, 8, 6] | -28.5 scores on a scale | Standard Deviation 19.01 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 48 [N=96, 43, 47] | -27.2 scores on a scale | Standard Deviation 21.44 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 100 [N=21, 13, 14] | -27.6 scores on a scale | Standard Deviation 21.85 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 60 [N=87, 40, 42] | -24.4 scores on a scale | Standard Deviation 24.23 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 112 [N=13, 8, 6] | -36.8 scores on a scale | Standard Deviation 38.84 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 60 [N=87, 40, 42] | -26.5 scores on a scale | Standard Deviation 25.63 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 72 [N=66, 33, 27] | -24.1 scores on a scale | Standard Deviation 32.14 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 88 [N=43, 25, 23] | -29.2 scores on a scale | Standard Deviation 23.95 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 124 [N=2, 1, 1] | -21.0 scores on a scale | — |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 100 [N=21, 13, 14] | -31.9 scores on a scale | Standard Deviation 24.45 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 24 [N=105, 57, 56] | -18.6 scores on a scale | Standard Deviation 24.42 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | End of Study Visit [N=103, 52, 54] | -18.6 scores on a scale | Standard Deviation 27.61 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 36 [N=100, 48, 48] | -20.0 scores on a scale | Standard Deviation 25.52 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study | Week 48 [N=96, 43, 47] | -23.6 scores on a scale | Standard Deviation 25.23 |
Secondary
Change From Baseline in Patient's Pain Intensity
The patient's assessment of pain was performed using a 100 mm visual analog scale (VAS) ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 4 [N=71, 64, 68, 70] | -9.1 scores on a scale | Standard Error 2.4 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 12 [N=71, 64, 68, 70] | -14.2 scores on a scale | Standard Error 2.72 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 2 [N=70, 64, 68, 70] | -6.7 scores on a scale | Standard Error 2.2 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 8 [N=71, 64, 68, 70] | -12.2 scores on a scale | Standard Error 2.66 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 2 [N=70, 64, 68, 70] | -8.0 scores on a scale | Standard Error 2.29 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 4 [N=71, 64, 68, 70] | -9.6 scores on a scale | Standard Error 2.52 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 8 [N=71, 64, 68, 70] | -12.5 scores on a scale | Standard Error 2.8 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity | Week 12 [N=71, 64, 68, 70] | -15.1 scores on a scale | Standard Error 2.87 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity | Week 2 [N=70, 64, 68, 70] | -8.3 scores on a scale | Standard Error 2.23 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity | Week 8 [N=71, 64, 68, 70] | -14.0 scores on a scale | Standard Error 2.72 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity | Week 4 [N=71, 64, 68, 70] | -11.4 scores on a scale | Standard Error 2.45 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity | Week 12 [N=71, 64, 68, 70] | -17.0 scores on a scale | Standard Error 2.78 |
| Placebo | Change From Baseline in Patient's Pain Intensity | Week 4 [N=71, 64, 68, 70] | -5.6 scores on a scale | Standard Error 2.45 |
| Placebo | Change From Baseline in Patient's Pain Intensity | Week 8 [N=71, 64, 68, 70] | -7.6 scores on a scale | Standard Error 2.72 |
| Placebo | Change From Baseline in Patient's Pain Intensity | Week 12 [N=71, 64, 68, 70] | -10.5 scores on a scale | Standard Error 2.78 |
| Placebo | Change From Baseline in Patient's Pain Intensity | Week 2 [N=70, 64, 68, 70] | -4.2 scores on a scale | Standard Error 2.22 |
Secondary
Change From Baseline in Patient's Pain Intensity During the Extension Study
The patient's assessment of pain was performed using a 100 mm visual analog scale (VAS) ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 24 [N=106, 57, 56] | -22.8 scores on a scale | Standard Deviation 26.44 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 36 [N=100, 48, 48] | -21.7 scores on a scale | Standard Deviation 29 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 48 [N=96, 43, 47] | -25.1 scores on a scale | Standard Deviation 28.08 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 60 [N=87, 40, 42] | -26.3 scores on a scale | Standard Deviation 27.09 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 72 [N=66, 34, 27] | -29.0 scores on a scale | Standard Deviation 27.42 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 88 [N=43, 25, 23] | -28.5 scores on a scale | Standard Deviation 30.42 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 100 [N=21, 13, 14] | -30.7 scores on a scale | Standard Deviation 23.6 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 112 [N=13, 8, 6] | -33.3 scores on a scale | Standard Deviation 20.38 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 124 [N=2, 1, 1] | -55.0 scores on a scale | Standard Deviation 15.56 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | End of Study Visit [N=103, 53, 54] | -19.1 scores on a scale | Standard Deviation 28.14 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 124 [N=2, 1, 1] | -17.0 scores on a scale | — |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 24 [N=106, 57, 56] | -24.1 scores on a scale | Standard Deviation 25.69 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 88 [N=43, 25, 23] | -29.0 scores on a scale | Standard Deviation 30.23 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 72 [N=66, 34, 27] | -35.2 scores on a scale | Standard Deviation 26.06 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 36 [N=100, 48, 48] | -28.2 scores on a scale | Standard Deviation 22.05 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | End of Study Visit [N=103, 53, 54] | -21.9 scores on a scale | Standard Deviation 27.19 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 112 [N=13, 8, 6] | -17.5 scores on a scale | Standard Deviation 25.39 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 48 [N=96, 43, 47] | -30.6 scores on a scale | Standard Deviation 21.94 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 100 [N=21, 13, 14] | -27.6 scores on a scale | Standard Deviation 26.14 |
| Canakinumab 300 mg q2wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 60 [N=87, 40, 42] | -27.8 scores on a scale | Standard Deviation 25.63 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 112 [N=13, 8, 6] | -31.7 scores on a scale | Standard Deviation 38.93 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 60 [N=87, 40, 42] | -30.0 scores on a scale | Standard Deviation 23.04 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 72 [N=66, 34, 27] | -26.2 scores on a scale | Standard Deviation 27.63 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 88 [N=43, 25, 23] | -32.3 scores on a scale | Standard Deviation 24.84 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 124 [N=2, 1, 1] | -24.0 scores on a scale | — |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 100 [N=21, 13, 14] | -32.0 scores on a scale | Standard Deviation 26.15 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 24 [N=106, 57, 56] | -20.8 scores on a scale | Standard Deviation 25.61 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | End of Study Visit [N=103, 53, 54] | -20.9 scores on a scale | Standard Deviation 27.45 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 36 [N=100, 48, 48] | -24.0 scores on a scale | Standard Deviation 24.13 |
| Canakinumab 150 mg q4wk | Change From Baseline in Patient's Pain Intensity During the Extension Study | Week 48 [N=96, 43, 47] | -21.1 scores on a scale | Standard Deviation 23.02 |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity
The physician's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment of disease activity when performing their own assessment on that patient. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 69] | -13.3 scores on a scale | Standard Error 2.21 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 4 [N=71, 64, 68, 70] | -17.7 scores on a scale | Standard Error 2.4 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 8 [N=71, 64, 68, 70] | -20.8 scores on a scale | Standard Error 2.68 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 12 [N=71, 64, 68, 70] | -21.6 scores on a scale | Standard Error 2.82 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 4 [N=71, 64, 68, 70] | -20.1 scores on a scale | Standard Error 2.55 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 8 [N=71, 64, 68, 70] | -22.6 scores on a scale | Standard Error 2.86 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 12 [N=71, 64, 68, 70] | -24.0 scores on a scale | Standard Error 3.01 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 69] | -14.8 scores on a scale | Standard Error 2.34 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 8 [N=71, 64, 68, 70] | -23.6 scores on a scale | Standard Error 2.75 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 4 [N=71, 64, 68, 70] | -20.3 scores on a scale | Standard Error 2.46 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 12 [N=71, 64, 68, 70] | -26.4 scores on a scale | Standard Error 2.9 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 69] | -15.2 scores on a scale | Standard Error 2.25 |
| Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 12 [N=71, 64, 68, 70] | -17.6 scores on a scale | Standard Error 2.88 |
| Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 4 [N=71, 64, 68, 70] | -12.2 scores on a scale | Standard Error 2.45 |
| Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 2 [N=70, 64, 68, 69] | -9.3 scores on a scale | Standard Error 2.25 |
| Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity | Week 8 [N=71, 64, 68, 70] | -16.5 scores on a scale | Standard Error 2.74 |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study
The physician's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment of disease activity when performing their own assessment on that patient. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 24 [N=105, 57, 55] | -30.9 scores on a scale | Standard Deviation 23.58 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 36 [N=98, 48, 48] | -31.1 scores on a scale | Standard Deviation 22.69 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 48 [N=93, 43, 47] | -34.3 scores on a scale | Standard Deviation 22.6 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 60 [N=89, 40, 43] | -34.9 scores on a scale | Standard Deviation 23.57 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 72 [N=66, 34, 27] | -37.7 scores on a scale | Standard Deviation 25.64 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 88 [N=42, 25, 22] | -41.9 scores on a scale | Standard Deviation 23.81 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 100 [N=21, 12, 13] | -45.2 scores on a scale | Standard Deviation 18.56 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 112 [N=13, 8, 6] | -45.2 scores on a scale | Standard Deviation 22.11 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 124 [N=2, 1, 1] | -54.5 scores on a scale | Standard Deviation 0.71 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | End of Study Visit [N=102, 53, 53] | -25.6 scores on a scale | Standard Deviation 27.23 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 124 [N=2, 1, 1] | -49.0 scores on a scale | — |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 24 [N=105, 57, 55] | -36.1 scores on a scale | Standard Deviation 25.59 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 88 [N=42, 25, 22] | -44.8 scores on a scale | Standard Deviation 19.42 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 72 [N=66, 34, 27] | -44.6 scores on a scale | Standard Deviation 22.32 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 36 [N=98, 48, 48] | -41.6 scores on a scale | Standard Deviation 18.24 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | End of Study Visit [N=102, 53, 53] | -29.7 scores on a scale | Standard Deviation 25.95 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 112 [N=13, 8, 6] | -51.4 scores on a scale | Standard Deviation 13.11 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 48 [N=93, 43, 47] | -45.6 scores on a scale | Standard Deviation 18.09 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 100 [N=21, 12, 13] | -42.2 scores on a scale | Standard Deviation 12.93 |
| Canakinumab 300 mg q2wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 60 [N=89, 40, 43] | -41.9 scores on a scale | Standard Deviation 22.92 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 112 [N=13, 8, 6] | -29.0 scores on a scale | Standard Deviation 33.15 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 60 [N=89, 40, 43] | -42.3 scores on a scale | Standard Deviation 24 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 72 [N=66, 34, 27] | -43.8 scores on a scale | Standard Deviation 18.34 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 88 [N=42, 25, 22] | -45.4 scores on a scale | Standard Deviation 19 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 124 [N=2, 1, 1] | -39.0 scores on a scale | — |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 100 [N=21, 12, 13] | -47.6 scores on a scale | Standard Deviation 17.04 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 24 [N=105, 57, 55] | -36.0 scores on a scale | Standard Deviation 23.94 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | End of Study Visit [N=102, 53, 53] | -31.8 scores on a scale | Standard Deviation 29.28 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 36 [N=98, 48, 48] | -37.3 scores on a scale | Standard Deviation 24.17 |
| Canakinumab 150 mg q4wk | Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study | Week 48 [N=93, 43, 47] | -38.8 scores on a scale | Standard Deviation 24.99 |
Secondary
Change From Baseline in Rheumatoid Factor Concentration
Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) that is an indicator of inflammation and rheumatoid arthritis.
Time frame: Baseline and Weeks 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Rheumatoid Factor Concentration | Week 12 [N=70, 64, 69, 70] | 2.0 kIU/L | Standard Deviation 135.7 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Rheumatoid Factor Concentration | Week 4 [N=70, 62, 68, 67] | -6.7 kIU/L | Standard Deviation 71.53 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Rheumatoid Factor Concentration | Week 8 [N=70, 63, 69, 70] | -2.6 kIU/L | Standard Deviation 117.3 |
| Canakinumab 300 mg q2wk | Change From Baseline in Rheumatoid Factor Concentration | Week 4 [N=70, 62, 68, 67] | -10.6 kIU/L | Standard Deviation 99.36 |
| Canakinumab 300 mg q2wk | Change From Baseline in Rheumatoid Factor Concentration | Week 12 [N=70, 64, 69, 70] | 29.7 kIU/L | Standard Deviation 144.91 |
| Canakinumab 300 mg q2wk | Change From Baseline in Rheumatoid Factor Concentration | Week 8 [N=70, 63, 69, 70] | 22.7 kIU/L | Standard Deviation 134.66 |
| Canakinumab 150 mg q4wk | Change From Baseline in Rheumatoid Factor Concentration | Week 8 [N=70, 63, 69, 70] | -57.1 kIU/L | Standard Deviation 442.24 |
| Canakinumab 150 mg q4wk | Change From Baseline in Rheumatoid Factor Concentration | Week 4 [N=70, 62, 68, 67] | -16.1 kIU/L | Standard Deviation 144.18 |
| Canakinumab 150 mg q4wk | Change From Baseline in Rheumatoid Factor Concentration | Week 12 [N=70, 64, 69, 70] | -50.7 kIU/L | Standard Deviation 531.68 |
| Placebo | Change From Baseline in Rheumatoid Factor Concentration | Week 4 [N=70, 62, 68, 67] | -0.9 kIU/L | Standard Deviation 85.28 |
| Placebo | Change From Baseline in Rheumatoid Factor Concentration | Week 12 [N=70, 64, 69, 70] | 16.9 kIU/L | Standard Deviation 110.03 |
| Placebo | Change From Baseline in Rheumatoid Factor Concentration | Week 8 [N=70, 63, 69, 70] | 6.0 kIU/L | Standard Deviation 91.51 |
Secondary
Change From Baseline in Short Form 36 Health Survey (SF-36)
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 2 [N=61, 61, 59, 64] | 0.56 scores on a scale | Standard Deviation 8.831 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 8 [N=67, 62, 63, 68] | 2.62 scores on a scale | Standard Deviation 6.528 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 12 [N=68, 62, 63, 68] | 4.03 scores on a scale | Standard Deviation 6.519 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 12 [N=68, 62, 63, 68] | 1.44 scores on a scale | Standard Deviation 9.988 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 8 [N=67, 62, 63, 68] | 2.29 scores on a scale | Standard Deviation 10.505 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 4 [N=65, 62, 63, 67] | 2.71 scores on a scale | Standard Deviation 6.582 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 2 [N=61, 61, 59, 64] | 1.73 scores on a scale | Standard Deviation 5.013 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 4 [N=65, 62, 63, 67] | 2.18 scores on a scale | Standard Deviation 9.66 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 8 [N=67, 62, 63, 68] | 2.75 scores on a scale | Standard Deviation 7.331 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 2 [N=61, 61, 59, 64] | 0.27 scores on a scale | Standard Deviation 5.648 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 4 [N=65, 62, 63, 67] | 2.30 scores on a scale | Standard Deviation 6.972 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 12 [N=68, 62, 63, 68] | 3.05 scores on a scale | Standard Deviation 7.847 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 2 [N=61, 61, 59, 64] | 2.64 scores on a scale | Standard Deviation 8.425 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 4 [N=65, 62, 63, 67] | 2.75 scores on a scale | Standard Deviation 11.364 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 8 [N=67, 62, 63, 68] | 2.83 scores on a scale | Standard Deviation 11.76 |
| Canakinumab 300 mg q2wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 12 [N=68, 62, 63, 68] | 3.34 scores on a scale | Standard Deviation 11.927 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 4 [N=65, 62, 63, 67] | 3.21 scores on a scale | Standard Deviation 6.406 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 12 [N=68, 62, 63, 68] | 4.06 scores on a scale | Standard Deviation 10.952 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 8 [N=67, 62, 63, 68] | 3.04 scores on a scale | Standard Deviation 9.307 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 2 [N=61, 61, 59, 64] | 1.21 scores on a scale | Standard Deviation 8.486 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 8 [N=67, 62, 63, 68] | 4.29 scores on a scale | Standard Deviation 8.757 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 4 [N=65, 62, 63, 67] | 2.23 scores on a scale | Standard Deviation 8.634 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 12 [N=68, 62, 63, 68] | 5.73 scores on a scale | Standard Deviation 8.612 |
| Canakinumab 150 mg q4wk | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 2 [N=61, 61, 59, 64] | 2.85 scores on a scale | Standard Deviation 4.999 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 12 [N=68, 62, 63, 68] | 2.69 scores on a scale | Standard Deviation 7.846 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 2 [N=61, 61, 59, 64] | 0.63 scores on a scale | Standard Deviation 9.234 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 12 [N=68, 62, 63, 68] | 0.35 scores on a scale | Standard Deviation 9.294 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 4 [N=65, 62, 63, 67] | 1.75 scores on a scale | Standard Deviation 8.331 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 2 [N=61, 61, 59, 64] | 2.03 scores on a scale | Standard Deviation 6.996 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 8 [N=67, 62, 63, 68] | 1.96 scores on a scale | Standard Deviation 7.464 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Mental component: Week 8 [N=67, 62, 63, 68] | 1.18 scores on a scale | Standard Deviation 9.58 |
| Placebo | Change From Baseline in Short Form 36 Health Survey (SF-36) | Physical component: Week 4 [N=65, 62, 63, 67] | 2.43 scores on a scale | Standard Deviation 7.134 |
Secondary
Change From Baseline in Swollen 28-joint Count
The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, the number of patients included in the analysis at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 2 [N=70, 64, 69, 70] | -2.4 swollen joints | Standard Error 0.53 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 4 [N=71, 64, 69, 70] | -3.4 swollen joints | Standard Error 0.55 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 8 [N=71, 64, 69, 70] | -4.0 swollen joints | Standard Error 0.58 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 12 [N=71, 64, 69, 70] | -4.6 swollen joints | Standard Error 0.64 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 4 [N=71, 64, 69, 70] | -4.0 swollen joints | Standard Error 0.58 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 8 [N=71, 64, 69, 70] | -4.4 swollen joints | Standard Error 0.61 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 12 [N=71, 64, 69, 70] | -5.3 swollen joints | Standard Error 0.67 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count | Week 2 [N=70, 64, 69, 70] | -2.7 swollen joints | Standard Error 0.56 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count | Week 8 [N=71, 64, 69, 70] | -4.9 swollen joints | Standard Error 0.59 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count | Week 4 [N=71, 64, 69, 70] | -4.6 swollen joints | Standard Error 0.56 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count | Week 12 [N=71, 64, 69, 70] | -5.2 swollen joints | Standard Error 0.65 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count | Week 2 [N=70, 64, 69, 70] | -3.1 swollen joints | Standard Error 0.54 |
| Placebo | Change From Baseline in Swollen 28-joint Count | Week 12 [N=71, 64, 69, 70] | -3.4 swollen joints | Standard Error 0.65 |
| Placebo | Change From Baseline in Swollen 28-joint Count | Week 4 [N=71, 64, 69, 70] | -3.0 swollen joints | Standard Error 0.56 |
| Placebo | Change From Baseline in Swollen 28-joint Count | Week 2 [N=70, 64, 69, 70] | -2.3 swollen joints | Standard Error 0.54 |
| Placebo | Change From Baseline in Swollen 28-joint Count | Week 8 [N=71, 64, 69, 70] | -3.3 swollen joints | Standard Error 0.59 |
Secondary
Change From Baseline in Swollen 28-joint Count During the Extension Study
The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2).
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 24 [N=105, 58, 55] | -6.04 swollen joints | Standard Deviation 4.892 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 36 [N=100, 49, 49] | -7.12 swollen joints | Standard Deviation 4.828 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 48 [N=95, 44, 47] | -7.72 swollen joints | Standard Deviation 4.171 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 60 [N=89, 40, 43] | -7.69 swollen joints | Standard Deviation 4.67 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 72 [N=66, 35, 27] | -7.41 swollen joints | Standard Deviation 5.311 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 88 [N=44, 25, 22] | -8.38 swollen joints | Standard Deviation 4.369 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 100 [N=21, 13, 14] | -8.29 swollen joints | Standard Deviation 4.285 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 112 [N=13, 8, 6] | -7.39 swollen joints | Standard Deviation 5.308 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 124 [N=2, 1, 1] | -6.50 swollen joints | Standard Deviation 0.707 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | End of Study Visit [N=103, 55, 53] | -6.36 swollen joints | Standard Deviation 5.477 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 124 [N=2, 1, 1] | -16.00 swollen joints | — |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 24 [N=105, 58, 55] | -5.70 swollen joints | Standard Deviation 5.119 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 88 [N=44, 25, 22] | -7.24 swollen joints | Standard Deviation 3.666 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 72 [N=66, 35, 27] | -7.94 swollen joints | Standard Deviation 4.143 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 36 [N=100, 49, 49] | -6.79 swollen joints | Standard Deviation 4.365 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | End of Study Visit [N=103, 55, 53] | -5.99 swollen joints | Standard Deviation 4.937 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 112 [N=13, 8, 6] | -9.50 swollen joints | Standard Deviation 2.976 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 48 [N=95, 44, 47] | -7.52 swollen joints | Standard Deviation 3.622 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 100 [N=21, 13, 14] | -8.15 swollen joints | Standard Deviation 2.824 |
| Canakinumab 300 mg q2wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 60 [N=89, 40, 43] | -7.38 swollen joints | Standard Deviation 3.737 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 112 [N=13, 8, 6] | -5.83 swollen joints | Standard Deviation 5.636 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 60 [N=89, 40, 43] | -8.65 swollen joints | Standard Deviation 4.825 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 72 [N=66, 35, 27] | -7.60 swollen joints | Standard Deviation 3.678 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 88 [N=44, 25, 22] | -7.50 swollen joints | Standard Deviation 3.389 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 124 [N=2, 1, 1] | -4.00 swollen joints | — |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 100 [N=21, 13, 14] | -7.56 swollen joints | Standard Deviation 2.974 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 24 [N=105, 58, 55] | -6.93 swollen joints | Standard Deviation 5.3 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | End of Study Visit [N=103, 55, 53] | -6.67 swollen joints | Standard Deviation 6.35 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 36 [N=100, 49, 49] | -7.05 swollen joints | Standard Deviation 4.726 |
| Canakinumab 150 mg q4wk | Change From Baseline in Swollen 28-joint Count During the Extension Study | Week 48 [N=95, 44, 47] | -7.74 swollen joints | Standard Deviation 4.454 |
Secondary
Change From Baseline in Tender 28-joint Count
The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: ITT Population, the number of patients included in the analysis at each time point is indicated by N. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 2 [N=70, 64, 69, 70] | -3.0 tender joints | Standard Error 0.68 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 4 [N=71, 64, 69, 70] | -4.1 tender joints | Standard Error 0.77 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 12 [N=71, 64, 69, 70] | -4.3 tender joints | Standard Error 0.86 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 8 [N=71, 64, 69, 70] | -4.6 tender joints | Standard Error 0.79 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 4 [N=71, 64, 69, 70] | -4.0 tender joints | Standard Error 0.8 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 12 [N=71, 64, 69, 70] | -4.8 tender joints | Standard Error 0.9 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 8 [N=71, 64, 69, 70] | -4.7 tender joints | Standard Error 0.83 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count | Week 2 [N=70, 64, 69, 70] | -2.1 tender joints | Standard Error 0.71 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count | Week 2 [N=70, 64, 69, 70] | -3.6 tender joints | Standard Error 0.68 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count | Week 12 [N=71, 64, 69, 70] | -6.3 tender joints | Standard Error 0.87 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count | Week 8 [N=71, 64, 69, 70] | -5.4 tender joints | Standard Error 0.8 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count | Week 4 [N=71, 64, 69, 70] | -5.0 tender joints | Standard Error 0.78 |
| Placebo | Change From Baseline in Tender 28-joint Count | Week 12 [N=71, 64, 69, 70] | -4.5 tender joints | Standard Error 0.87 |
| Placebo | Change From Baseline in Tender 28-joint Count | Week 2 [N=70, 64, 69, 70] | -3.2 tender joints | Standard Error 0.69 |
| Placebo | Change From Baseline in Tender 28-joint Count | Week 4 [N=71, 64, 69, 70] | -4.2 tender joints | Standard Error 0.78 |
| Placebo | Change From Baseline in Tender 28-joint Count | Week 8 [N=71, 64, 69, 70] | -4.7 tender joints | Standard Error 0.8 |
Secondary
Change From Baseline in Tender 28-joint Count During the Extension Study
The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2).
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 24 [N=105, 58, 55] | -6.93 tender joints | Standard Deviation 7.078 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 36 [N=100, 49, 49] | -7.92 tender joints | Standard Deviation 6.793 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 48 [N=95, 44, 47] | -8.64 tender joints | Standard Deviation 7.193 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 60 [N=89, 40, 43] | -8.52 tender joints | Standard Deviation 6.915 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 72 [N=66, 35, 27] | -8.71 tender joints | Standard Deviation 7.556 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 88 [N=44, 25, 22] | -10.34 tender joints | Standard Deviation 5.995 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 100 [N=21, 13, 14] | -8.53 tender joints | Standard Deviation 5.78 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 112 [N=13, 8, 6] | -8.47 tender joints | Standard Deviation 6.205 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 124 [N=2, 1, 1] | -9.00 tender joints | Standard Deviation 4.243 |
| Canakinumab 600 mg IV + 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | End of Study Visit [N=103, 55, 53] | -7.93 tender joints | Standard Deviation 7.857 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 124 [N=2, 1, 1] | -23.00 tender joints | — |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 24 [N=105, 58, 55] | -8.27 tender joints | Standard Deviation 7.555 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 88 [N=44, 25, 22] | -10.76 tender joints | Standard Deviation 7.184 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 72 [N=66, 35, 27] | -11.37 tender joints | Standard Deviation 7.436 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 36 [N=100, 49, 49] | -9.83 tender joints | Standard Deviation 6.459 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | End of Study Visit [N=103, 55, 53] | -8.43 tender joints | Standard Deviation 8.331 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 112 [N=13, 8, 6] | -13.63 tender joints | Standard Deviation 6.435 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 48 [N=95, 44, 47] | -10.75 tender joints | Standard Deviation 5.948 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 100 [N=21, 13, 14] | -12.00 tender joints | Standard Deviation 5.307 |
| Canakinumab 300 mg q2wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 60 [N=89, 40, 43] | -11.10 tender joints | Standard Deviation 6.484 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 112 [N=13, 8, 6] | -9.17 tender joints | Standard Deviation 5.981 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 60 [N=89, 40, 43] | -10.76 tender joints | Standard Deviation 6.185 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 72 [N=66, 35, 27] | -9.56 tender joints | Standard Deviation 4.722 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 88 [N=44, 25, 22] | -9.98 tender joints | Standard Deviation 4.964 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 124 [N=2, 1, 1] | -8.00 tender joints | — |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 100 [N=21, 13, 14] | -9.08 tender joints | Standard Deviation 4.989 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 24 [N=105, 58, 55] | -8.49 tender joints | Standard Deviation 7.298 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | End of Study Visit [N=103, 55, 53] | -8.83 tender joints | Standard Deviation 7.573 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 36 [N=100, 49, 49] | -8.95 tender joints | Standard Deviation 7.154 |
| Canakinumab 150 mg q4wk | Change From Baseline in Tender 28-joint Count During the Extension Study | Week 48 [N=95, 44, 47] | -10.05 tender joints | Standard Deviation 6.321 |
Secondary
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study
To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, patients were categorized as follows: 1. Did not attain an ACR20 response; 2. Attained a 20% but not a 50% response; 3. Attained a 50% but not a 70% response; 4. Attained a 70% or greater response. A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire \[HAQ\] score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]).
Time frame: Baseline and End of Study (up to 124 weeks)
Population: Extension Study ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | No response | 50 participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR20 - not ACR50 response | 29 participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR50 - not ACR70 response | 10 participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR70 response | 14 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR70 response | 9 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | No response | 24 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR50 - not ACR70 response | 10 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR20 - not ACR50 response | 10 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR70 response | 7 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR20 - not ACR50 response | 14 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | ACR50 - not ACR70 response | 12 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study | No response | 21 participants |
Secondary
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12
To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, participants were categorized as follows: 1. Did not attain an ACR20 response; 2. Attained a 20% but not a 50% response; 3. Attained a 50% but not a 70% response; 4. Attained a 70% or greater response. A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire \[HAQ\] score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]).
Time frame: Baseline and Week 12
Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR evaluation. Last observation carried forward was applied for all the component variables.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | No response | 40 participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR20 - not ACR50 response | 24 participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR50 - not ACR70 response | 4 participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR70 response | 3 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR20 - not ACR50 response | 16 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR70 response | 2 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | No response | 33 participants |
| Canakinumab 300 mg q2wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR50 - not ACR70 response | 13 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR50 - not ACR70 response | 14 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR70 response | 4 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | No response | 34 participants |
| Canakinumab 150 mg q4wk | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR20 - not ACR50 response | 16 participants |
| Placebo | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR70 response | 2 participants |
| Placebo | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | No response | 50 participants |
| Placebo | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR20 - not ACR50 response | 12 participants |
| Placebo | Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR50 - not ACR70 response | 6 participants |
Secondary
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders
Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered ACR20 non-responders if they failed the ACR20 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR20 evaluation. Last observation carried forward was applied for all the component variables. N indicates the number of patients included at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 17.1 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 4 [N=71, 64, 68, 70] | 29.6 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 8 [N=71, 64, 68, 70] | 35.2 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 12 [N=71, 64, 68, 70] | 43.7 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 4 [N=71, 64, 68, 70] | 37.5 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 8 [N=71, 64, 68, 70] | 43.8 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 12 [N=71, 64, 68, 70] | 48.4 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 29.7 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 8 [N=71, 64, 68, 70] | 42.6 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 4 [N=71, 64, 68, 70] | 39.7 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 12 [N=71, 64, 68, 70] | 50.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 23.2 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 12 [N=71, 64, 68, 70] | 28.6 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 4 [N=71, 64, 68, 70] | 20.0 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 14.3 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Responders at Week 8 [N=71, 64, 68, 70] | 27.1 percentage of participants |
Secondary
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Time frame: Baseline and Weeks 2, 4 and 8
Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR50 evaluation. Last observation carried forward was applied for all the component variables. N indicates the number of patients included at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 8 [N=71, 64, 69, 70] | 4.2 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 4 [N=71, 64, 69, 70] | 1.4 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 2 [N=70, 64, 69, 70] | 2.9 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 8 [N=71, 64, 69, 70] | 17.2 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 2 [N=70, 64, 69, 70] | 1.6 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 4 [N=71, 64, 69, 70] | 7.8 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 8 [N=71, 64, 69, 70] | 17.4 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 4 [N=71, 64, 69, 70] | 7.2 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 2 [N=70, 64, 69, 70] | 5.8 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 8 [N=71, 64, 69, 70] | 7.1 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 4 [N=71, 64, 69, 70] | 4.3 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 | Responders at Week 2 [N=70, 64, 69, 70] | 4.3 percentage of participants |
Secondary
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders
Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered ACR70 non-responders if they failed the ACR70 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders.
Time frame: Baseline and Weeks 2, 4, 8 and 12
Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR70 evaluation. Last observation carried forward was applied for all the component variables. N indicates the number of patients included at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 0.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 4 [N=71, 64, 69, 70] | 0.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 8 [N=71, 64, 69, 70] | 0.0 percentage of participants |
| Canakinumab 600 mg IV + 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 12 [N=71, 64, 69, 70] | 4.2 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 4 [N=71, 64, 69, 70] | 1.6 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 12 [N=71, 64, 69, 70] | 3.1 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 1.6 percentage of participants |
| Canakinumab 300 mg q2wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 8 [N=71, 64, 69, 70] | 4.7 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 0.0 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 12 [N=71, 64, 69, 70] | 5.8 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 8 [N=71, 64, 69, 70] | 5.8 percentage of participants |
| Canakinumab 150 mg q4wk | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 4 [N=71, 64, 69, 70] | 4.3 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 12 [N=71, 64, 69, 70] | 2.9 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 2 [N=70, 64, 69, 70] | 0.0 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 4 [N=71, 64, 69, 70] | 0.0 percentage of participants |
| Placebo | Percentage of American College of Rheumatology [ACR] 70 Criteria Responders | Responders at Week 8 [N=71, 64, 69, 70] | 2.9 percentage of participants |