Acute Gout
Conditions
Keywords
frequent flares, gout, anti-interleukin-1β monoclonal antibody
Brief summary
The purpose of the 12-week core study was to demonstrate that canakinumab given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares in patients with frequent flares of gout for whom non-steroidal anti-inflammatory drugs (NSAIDs) and/ or colchicine are contraindicated, not tolerated, or ineffective. The efficacy of canakinumab was compared to the corticosteroid triamcinolone acetonide. The purpose of the first 12-week extension study was to collect additional safety, tolerability and efficacy data in patients who have completed the core study CACZ885H2356. The purpose of the second 48 week open-label extension study was to collect additional long-term safety and tolerability data in patients who have completed the first extension study CACZ885H2356E1.
Detailed description
Masking: Core: Double Blind (Subject, Investigator) Extension 1: Double Blind (Subject, Investigator) Extension 2: Open-label, terminated
Interventions
Canakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill).
Triamcinolone acetonide 40 mg was supplied as a suspension.
Placebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake.
Placebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Core Study: Inclusion criteria: * Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout * Onset of current acute gout flare within 5 days prior to study entry * Baseline pain intensity ≥ 50 mm on the 0-100 mm visual analog scale (VAS) * History of ≥ 3 gout flares within the 12 months prior to study entry * Contraindication, intolerance, or lack of efficacy for non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine
Exclusion criteria
* Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis * Presence of severe renal function impairment * Use of specified pain relief medications or biologics ( corticosteroids, narcotics, paracetamol/acetominophen, ibuprofen, colchicine, IL-blocker, and tumor necrosis factor inhibitor) within specified periods prior to study entry * Live vaccinations within 3 months prior to randomization * Requirement for administration of antibiotics against latent tuberculosis (TB) * Refractory heart failure (Stage D) * Unstable cardiac arrhythmias or unstable symptomatic coronary ischemia * Any active or recurrent bacterial, fungal, or viral infection Extension Study 1: Inclusion Completion of the Core study. A patient was defined as completing the core study if they completed the study up to and including visit 7. Exclusion \- Continuation in this extension study was considered inappropriate by the treating physician. Extension Study 2: Inclusion Completed of the first extension study CACZ885H2356E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10). Exclusion -Continuation in this extension study was considered inappropriate by the treating physician Other protocol-defined inclusion-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First New Flare | 12 weeks | Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before flare has resolved completely. |
| Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) | 72 hours post-dose (randomization) | Patients scored their pain intensity in the joint most affected at baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), at 72 hours post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates. |
| Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) | 24 weeks overall | This was the primary endpoint of both extension studies. Adverse event is defined as any unfavorable and unintended diagnosis, symptom, sign(including an abnormal laboratory finding),syndrome or disease which either occurs during the study, having been absent at baseline, or,if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. |
| Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | 72 weeks overall | This was the primary endpoint of both extension studies. Adverse event is defined as any unfavorable and unintended diagnosis, symptom, sign(including an abnormal laboratory finding),syndrome or disease which either occurs during the study, having been absent at baseline, or,if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of New Gout Flares Per Patient | 12 weeks | Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely. |
| SF36 Physical Function Score at Week 12 | Week 12 | The SF-36 measures the impact of disease on overall quality of life (QoL). This 36-item survey has 8 subscales that can be aggregated into physical- and mental-component summary scores. Scores are standardized with the use of norm-based methods based on an assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL. A negative change score indicates improvement. An ANCOVA model was used with treatment group and baseline SF-36 physical function subscore as covariates. |
| Time to First New Flare | 24 weeks | Kaplan-Meier (KM) estimates of time to first new flare and confidence intervals were determined. Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely. |
| Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study | 24 weeks | Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely. |
| Time to First Intake of Rescue Medication After the Last Post Baseline Flare. | 72 hours post-dose for the last post-baseline flare (during 24 weeks overall) | The Kaplan-Meier estimates of medians and 95% confidence intervals were used to calculate the endpoint. |
| Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension | 72 hours post-dose for the last post-baseline flare (during 24 weeks overall) | Patients scored their pain intensity in the joint most affected at baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates. |
| Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Last post-baseline flare (during 24 weeks overall) | Maximum severity is the maximum Likert score recorded after the start of the flare. Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme). |
| Amount of Rescue Medication Taken | 7 days last post-baseline flare (during 24 weeks) | Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows: * Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed. * If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolon as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare. |
| Percentage of Participants Who Took Rescue Medication | during 12 weeks core, 24 weeks overall | Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments. Permitted rescue medications included acetaminophen 500 mg and/ or codeine 30 mg as needed. If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolone as needed per day for 2 days followed by up to 20 mg of prednisolone as needed per day for 3 subsequent days within 7 days after randomization or after re-dose/injection administration. |
| High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall) | High sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The analysis included treatment group, log-transformed protein level at baseline, and body mass index (BMI) at baseline as covariates. |
| Physician's Global Assessment of Response to Treatment | 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall) | The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity \[Visual Analog Scale and Likert scale\] and patient's global assessment of response to treatment). |
| Patient's Global Assessment of Response to Treatment | 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall) | Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured. |
| Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) | From baseline to 7 days post dose (randomization) | The Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at baseline was determined along with the 95% confidence interval. Patients scored their pain intensity on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose. |
| Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall) | The study physician assessed the range of motion of the most affected joint for range of motion on a 5-point Likert scale: Normal, mildly restricted, moderately restricted, severely restricted, immobilized. The percentage of patients in each category is reported. |
| Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | 7 days post dose (randomization), 24 weeks post-dose | Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme). |
| Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall) | 72 weeks overall | Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before flare has resolved completely. |
| Flare Rate Per Year | 72 weeks overall | Flare rate was calculated as the number of new flares over the period of observation in years. Flare rate was calculated using only those new flares before switching to canakinumab. Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely. |
| High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall) | High sensitivity C-reactive protein (hsCRP) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall) | Serum Amyloid A Protein (SAA) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | 72 hours post-dose , 7 days post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall) | The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity \[Visual Analog Scale and Likert scale\] and patient's global assessment of response to treatment). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | 72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall) | Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | 72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall) | Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | 72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall) | The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that there is pain, patient states there is pain and winces, and patient states there is pain, winces, and withdraws on palpation or passive movement of the affected study joint; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | 72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall) | The study physician assessed the most affected joint for: Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | 72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall) | The study physician assessed the most affected joint for Erythema: Present or absent. The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab. |
| Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall) | The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that there is pain, patient states there is pain and winces, and patient states there is pain, winces, and withdraws on palpation or passive movement of the affected study joint; Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; and Erythema: Present or absent. The percentage of patients in each category is reported. |
| Time to Complete Resolution of Pain | 7 days post-dose (randomization) | Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose. The Kaplan-Meier estimates of time to complete resolution of self-assessed pain intensity in the joint most affected and their confidence intervals were determined. |
| Percentage of Participants With Complete Resolution of Pain | 7 days post-dose (randomization) | Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose. Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. The Kaplan-Meier estimates of cumulative event rate = percentage of participants with event up to the end of the time interval. |
| Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks | 12 weeks | Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely. |
Countries
Australia, Belgium, Canada, Colombia, Estonia, Germany, Guatemala, Latvia, Lithuania, Mexico, Norway, Poland, Russia, Singapore, Sweden, Switzerland, Ukraine
Participant flow
Pre-assignment details
Two patients randomized to canakinumab did not receive any study medication and were discontinued from the core study on the day of randomization, with the reason for discontinuation listed as Administrative Problems.
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab 150 mg Patients received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Patients could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Patients completing the 12 weeks core study were allowed to continue to be treated in another 12 weeks extension study for any new gout flare on demand with the same treatment as assigned in the core study. | 113 |
| Triamcinolone Acetonide 40 mg Patients received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Patients could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Patients completing the 12 weeks core study were allowed to continue to be treated in another 12 weeks extension study for any new gout flare on demand with the same treatment as assigned in the core study. | 115 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Study (0-12 Weeks) | Administrative problems | 2 | 1 |
| Core Study (0-12 Weeks) | Death | 0 | 1 |
| Core Study (0-12 Weeks) | Lost to Follow-up | 3 | 1 |
| Core Study (0-12 Weeks) | Patient Withdrew Consent | 1 | 3 |
| Core Study (0-12 Weeks) | Unsatisfactory therapeutic effect | 0 | 4 |
| Extension Study 1 (12-24 Weeks) | Lost to Follow-up | 2 | 3 |
| Extension Study 1 (12-24 Weeks) | Protocol Deviation | 1 | 0 |
| Extension Study 1 (12-24 Weeks) | Unsatisfactory therapeutic effect | 0 | 1 |
| Extension Study 1 (12-24 Weeks) | Withdrawal by Subject | 0 | 1 |
| Extension Study 2 (25-72 Weeks) | Death | 1 | 1 |
| Extension Study 2 (25-72 Weeks) | Unsatisfactory therapeutic effect | 0 | 1 |
| Extension Study 2 (25-72 Weeks) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Canakinumab 150 mg | Triamcinolone Acetonide 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 11.18 | 54.6 years STANDARD_DEVIATION 10.71 | 54.3 years STANDARD_DEVIATION 10.93 |
| Age, Customized ≥ 65 - 74 years | 16 participants | 21 participants | 37 participants |
| Age, Customized < 65 years | 92 participants | 92 participants | 184 participants |
| Age, Customized ≥ 75 years | 5 participants | 2 participants | 7 participants |
| Sex: Female, Male Female | 12 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Male | 101 Participants | 108 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 113 | 19 / 69 | 19 / 69 | 22 / 115 | 7 / 39 | 12 / 39 |
| serious Total, serious adverse events | 19 / 113 | 6 / 69 | 8 / 69 | 11 / 115 | 2 / 39 | 0 / 39 |
Outcome results
Primary
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall)
This was the primary endpoint of both extension studies. Adverse event is defined as any unfavorable and unintended diagnosis, symptom, sign(including an abnormal laboratory finding),syndrome or disease which either occurs during the study, having been absent at baseline, or,if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: 24 weeks overall
Population: Safety population consisted of all patients who received study drug in the core study and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) | Adverse Event | 71 Participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) | Death | 0 Participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) | Serious Adverse Event | 11 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) | Adverse Event | 56 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) | Death | 1 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall) | Serious Adverse Event | 6 Participants |
Primary
Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall)
This was the primary endpoint of both extension studies. Adverse event is defined as any unfavorable and unintended diagnosis, symptom, sign(including an abnormal laboratory finding),syndrome or disease which either occurs during the study, having been absent at baseline, or,if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: 72 weeks overall
Population: Safety population consisted of all patients who received study drug in the core study and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Death | 1 Participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Adverse Event | 76 Participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Serious Adverse Event | 19 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Adverse Event | 41 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Serious Adverse Event | 6 Participants |
| Randomized to Canakinumab :After Re-treated With Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Death | 1 Participants |
| Randomized to Canakinumab :After Re-treated With Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Adverse Event | 38 Participants |
| Randomized to Canakinumab :After Re-treated With Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Serious Adverse Event | 8 Participants |
| Randomized to Triamcinolone Acetonide (Triam) | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Death | 2 Participants |
| Randomized to Triamcinolone Acetonide (Triam) | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Adverse Event | 60 Participants |
| Randomized to Triamcinolone Acetonide (Triam) | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Serious Adverse Event | 11 Participants |
| Randomized to Triam: Before Switched to Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 Participants |
| Randomized to Triam: Before Switched to Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Adverse Event | 20 Participants |
| Randomized to Triam: Before Switched to Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Serious Adverse Event | 2 Participants |
| Randomized to Triam: After Switched to Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Adverse Event | 19 Participants |
| Randomized to Triam: After Switched to Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Serious Adverse Event | 0 Participants |
| Randomized to Triam: After Switched to Canakinumab | Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 Participants |
Primary
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS)
Patients scored their pain intensity in the joint most affected at baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), at 72 hours post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
Time frame: 72 hours post-dose (randomization)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. Last Observation Carried Forward (LOCF) method was used to impute post dose measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) | 28.1 mm | Standard Error 2.42 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) | 39.5 mm | Standard Error 2.44 |
Primary
Time to First New Flare
Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before flare has resolved completely.
Time frame: 12 weeks
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab 150 mg | Time to First New Flare | NA Days |
| Triamcinolone Acetonide 40 mg | Time to First New Flare | NA Days |
Secondary
Amount of Rescue Medication Taken
Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows: * Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed. * If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolon as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare.
Time frame: 7 days last post-baseline flare (during 24 weeks)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. Patients with observations at 7 days last post-baseline flare were included in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Acetaminophen | 1931.4 mg | Standard Deviation 3266.12 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Codeine | 7.7 mg | Standard Deviation 25.56 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Prednisolone/Prednisone | 4.1 mg | Standard Deviation 17.34 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Acetaminophen | 2058.1 mg | Standard Deviation 3331.33 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Codeine | 46.0 mg | Standard Deviation 118.26 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Prednisolone/Prednisone | 21.6 mg | Standard Deviation 47.42 |
Secondary
Flare Rate Per Year
Flare rate was calculated as the number of new flares over the period of observation in years. Flare rate was calculated using only those new flares before switching to canakinumab. Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
Time frame: 72 weeks overall
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | Flare Rate Per Year | 1.16 New flares per patient per year | Standard Deviation 1.511 |
| Triamcinolone Acetonide 40 mg | Flare Rate Per Year | 2.81 New flares per patient per year | Standard Deviation 4.399 |
Secondary
High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall
High sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The analysis included treatment group, log-transformed protein level at baseline, and body mass index (BMI) at baseline as covariates.
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in core study who had taken at least one dose of study drug. Patients with baseline flare and data at 72 hours post-dose in core and patients with a new flare and data at 72 hours post-dose for the last post-baseline flare (during 24 weeks overall) were included in this analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | hsCRP : Core(n= 109, 107) | 4.50 mg/L |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | SAA protein : Core (n=105, 106) | 6.77 mg/L |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | hsCRP : 24 weeks(n= 31, 32) | 5.18 mg/L |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | SAA protein : 24 weeks (n=28, 33) | 11.43 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | SAA protein : 24 weeks (n=28, 33) | 21.11 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | hsCRP : Core(n= 109, 107) | 7.08 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | hsCRP : 24 weeks(n= 31, 32) | 7.18 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall | SAA protein : Core (n=105, 106) | 17.00 mg/L |
Secondary
High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab
High sensitivity C-reactive protein (hsCRP) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 24 hours post dose (n= 45, 24) | 28.9 mg/L | Standard Deviation 42.26 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 72 hours post dose (n=45, 34) | 10.6 mg/L | Standard Deviation 14.69 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 7 days post dose (n=67, 39) | 3.3 mg/L | Standard Deviation 3.38 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 4 weeks post dose (n=52, 35) | 9.2 mg/L | Standard Deviation 48.57 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 8 weeks post dose (n=45, 37) | 2.6 mg/L | Standard Deviation 3 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 12 weeks post dose (n=42, 33) | 6.5 mg/L | Standard Deviation 12.99 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 8 weeks post dose (n=45, 37) | 3.0 mg/L | Standard Deviation 6.74 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 24 hours post dose (n= 45, 24) | 26.0 mg/L | Standard Deviation 29.07 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 4 weeks post dose (n=52, 35) | 3.2 mg/L | Standard Deviation 4.95 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 72 hours post dose (n=45, 34) | 7.0 mg/L | Standard Deviation 8.06 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 12 weeks post dose (n=42, 33) | 4.3 mg/L | Standard Deviation 11.9 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab | 7 days post dose (n=67, 39) | 3.2 mg/L | Standard Deviation 3.57 |
Secondary
Mean Number of New Gout Flares Per Patient
Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
Time frame: 12 weeks
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | Mean Number of New Gout Flares Per Patient | 0.21 New flares/patient/12 weeks | Standard Deviation 0.472 |
| Triamcinolone Acetonide 40 mg | Mean Number of New Gout Flares Per Patient | 0.53 New flares/patient/12 weeks | Standard Deviation 0.892 |
Secondary
Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study
Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
Time frame: 24 weeks
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study | 0.40 New flares/patient/24 weeks | Standard Deviation 0.634 |
| Triamcinolone Acetonide 40 mg | Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study | 0.87 New flares/patient/24 weeks | Standard Deviation 1.104 |
Secondary
Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale)
Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | None (72 hours post dose) (n=66, 39) | 19.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Mild (72 hours post dose) (n=66, 39) | 30.0 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Moderate (72 hours post dose) (n=66, 39) | 45.5 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Severe (72 hours post dose) (n=66, 39) | 4.5 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Extreme (72 hours post dose) (n=66, 39) | 0.0 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | None (7 days post dose) (n=65, 35) | 41.5 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Mild (7 days post dose) (n=65, 35) | 38.5 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Moderate (7 days post dose) (n=65, 35) | 18.5 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Severe (7 days post dose) (n=65, 35) | 1.5 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Extreme (7 days post dose) (n=65, 35) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Moderate (7 days post dose) (n=65, 35) | 5.7 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | None (72 hours post dose) (n=66, 39) | 20.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | None (7 days post dose) (n=65, 35) | 57.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Mild (72 hours post dose) (n=66, 39) | 61.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Extreme (7 days post dose) (n=65, 35) | 2.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Moderate (72 hours post dose) (n=66, 39) | 15.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Mild (7 days post dose) (n=65, 35) | 34.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Severe (72 hours post dose) (n=66, 39) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Severe (7 days post dose) (n=65, 35) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale) | Extreme (72 hours post dose) (n=66, 39) | 2.6 Percentage of participants |
Secondary
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale)
Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme).
Time frame: 7 days post dose (randomization), 24 weeks post-dose
Population: Full Analysis Set includes all patients that received study drug. 'N' in each category indicates participants with observations analyzed for this endpoint at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | None (7 days post-dose) [N= 110, 107] | 32.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Mild (7 days post-dose) [N= 110, 107] | 48.2 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Moderate (7 days post-dose) [N= 110, 107] | 16.4 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Severe (7 days post-dose) [N= 110, 107] | 2.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Extreme (7 days post-dose) [N= 110, 107] | 0.0 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | None (24 weeks post-dose) [N= 85, 78] | 47.1 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Mild (24 weeks post-dose) [N= 85, 78] | 38.8 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Moderate (24 weeks post-dose) [N= 85, 78] | 12.9 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Severe (24 weeks post-dose) [N= 85, 78] | 1.2 Percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Extreme (24 weeks post-dose) [N= 85, 78] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Moderate (24 weeks post-dose) [N= 85, 78] | 15.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | None (7 days post-dose) [N= 110, 107] | 28.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | None (24 weeks post-dose) [N= 85, 78] | 46.2 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Mild (7 days post-dose) [N= 110, 107] | 41.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Extreme (24 weeks post-dose) [N= 85, 78] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Moderate (7 days post-dose) [N= 110, 107] | 16.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Mild (24 weeks post-dose) [N= 85, 78] | 37.2 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Severe (7 days post-dose) [N= 110, 107] | 12.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Severe (24 weeks post-dose) [N= 85, 78] | 1.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale) | Extreme (7 days post-dose) [N= 110, 107] | 1.9 Percentage of participants |
Secondary
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension
Patients scored their pain intensity in the joint most affected at baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
Time frame: 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. Last Observation Carried Forward (LOCF) method was applied to impute post dose measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension | 34.6 mm | Standard Error 4.35 |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension | 44.9 mm | Standard Error 4.01 |
Secondary
Patient's Global Assessment of Response to Treatment
Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured.
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. 'N' in each category indicates participants with observations analyzed for this endpoint at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Slight (24 weeks) [N=87, 78] | 1.1 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Excellent (Core) [N=113, 111] | 12.4 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Acceptable (Core) [N=113, 111] | 37.2 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Slight (Core) [N=113, 111] | 8.8 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Poor (Core) [N=113, 111] | 2.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Excellent (24 weeks) [N=87, 78] | 31 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Good (24 weeks) [N=87, 78] | 46 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Acceptable (24 weeks) [N=87, 78] | 20.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Poor (24 weeks) [N=87, 78] | 1.1 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | Good (Core) [N=113, 111] | 38.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Acceptable (24 weeks) [N=87, 78] | 25.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Excellent (24 weeks) [N=87, 78] | 17.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Excellent (Core) [N=113, 111] | 12.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Good (Core) [N=113, 111] | 28.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Slight (24 weeks) [N=87, 78] | 9.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Acceptable (Core) [N=113, 111] | 30.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Good (24 weeks) [N=87, 78] | 44.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Slight (Core) [N=113, 111] | 12.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Poor (24 weeks) [N=87, 78] | 2.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | Poor (Core) [N=113, 111] | 15.3 Percentage of participants |
Secondary
Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Excellent (72 hours post dose) (n=60, 36) | 15.0 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (72 hours post dose) (n=60, 36) | 26.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Acceptable (72 hours post dose) (n=60, 36) | 50.0 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Slight (72 hours post dose) (n=60, 36) | 6.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (72 hours post dose) (n=60, 36) | 1.7 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Excellent (7 days post dose) (n=68, 36) | 23.5 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (7 days post dose) (n=68, 36) | 41.2 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Acceptable (7 days post dose) (n=68, 36) | 27.9 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Slight (7 days post dose) (n=68, 36) | 7.4 Percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (7 days post dose) (n=68, 36) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Acceptable (7 days post dose) (n=68, 36) | 16.7 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Excellent (72 hours post dose) (n=60, 36) | 19.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Excellent (7 days post dose) (n=68, 36) | 27.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (72 hours post dose) (n=60, 36) | 44.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (7 days post dose) (n=68, 36) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Acceptable (72 hours post dose) (n=60, 36) | 27.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (7 days post dose) (n=68, 36) | 52.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Slight (72 hours post dose) (n=60, 36) | 2.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Slight (7 days post dose) (n=68, 36) | 2.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (72 hours post dose) (n=60, 36) | 5.6 Percentage of participants |
Secondary
Percentage of Participants Who Took Rescue Medication
Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments. Permitted rescue medications included acetaminophen 500 mg and/ or codeine 30 mg as needed. If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolone as needed per day for 2 days followed by up to 20 mg of prednisolone as needed per day for 3 subsequent days within 7 days after randomization or after re-dose/injection administration.
Time frame: during 12 weeks core, 24 weeks overall
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in core study who had taken at least one dose of study drug. 12 weeks:Core consisted of patients taking rescue medication during baseline flare of Core study and 24 weeks:Overall consisted of patients who took rescue medication during last post-baseline flare during 24 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Percentage of Participants Who Took Rescue Medication | 12 weeks :Core (N=113, 115) | 31.0 Percentage of participants |
| Canakinumab 150 mg | Percentage of Participants Who Took Rescue Medication | 24 weeks: Overall (N=35, 43) | 48.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants Who Took Rescue Medication | 12 weeks :Core (N=113, 115) | 52.2 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants Who Took Rescue Medication | 24 weeks: Overall (N=35, 43) | 44.2 Percentage of participants |
Secondary
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks
Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
Time frame: 12 weeks
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab 150 mg | Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks | 18.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks | 34.8 Percentage of participants |
Secondary
Percentage of Participants With Complete Resolution of Pain
Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose. Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. The Kaplan-Meier estimates of cumulative event rate = percentage of participants with event up to the end of the time interval.
Time frame: 7 days post-dose (randomization)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab 150 mg | Percentage of Participants With Complete Resolution of Pain | 34.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With Complete Resolution of Pain | 31.3 Percentage of participants |
Secondary
Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale)
Maximum severity is the maximum Likert score recorded after the start of the flare. Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme).
Time frame: Last post-baseline flare (during 24 weeks overall)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. Participants with baseline and last post-baseline observations were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Mild | 0.0 Percentage of participants |
| Canakinumab 150 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Severe | 77.1 Percentage of participants |
| Canakinumab 150 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Moderate | 14.3 Percentage of participants |
| Canakinumab 150 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Extreme | 8.6 Percentage of participants |
| Canakinumab 150 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | None | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Extreme | 20.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | None | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Mild | 2.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Moderate | 16.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale) | Severe | 60.5 Percentage of participants |
Secondary
Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab
The study physician assessed the most affected joint for Erythema: Present or absent. The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Absent (72 hours post dose) (n=61, 35) | 82.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Present (72 hours post dose) (n=61, 35) | 18.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Absent (7 days post dose) (n=67, 36) | 95.5 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Present (7 days post dose) (n=67, 36) | 4.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Present (7 days post dose) (n=67, 36) | 5.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Absent (72 hours post dose) (n=61, 35) | 80.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Absent (7 days post dose) (n=67, 36) | 94.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab | Present (72 hours post dose) (n=61, 35) | 20.0 Percentage of participants |
Secondary
Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab
The study physician assessed the most affected joint for: Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | No Pain (72 hours post dose) (n=61, 35) | 29.5 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain (72 hours post dose) (n=61, 35) | 42.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain and winces (72 hours post dose) (n=61, 35) | 24.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=61, 35) | 3.3 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | No pain (7 days post dose) (n=68, 36) | 64.7 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain (7 days post dose) (n=68, 36) | 25.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain and winces (7 days post dose) (n=68, 36) | 7.4 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=68, 36) | 2.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=68, 36) | 2.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | No Pain (72 hours post dose) (n=61, 35) | 42.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | No pain (7 days post dose) (n=68, 36) | 75.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain (72 hours post dose) (n=61, 35) | 48.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain and winces (7 days post dose) (n=68, 36) | 5.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain and winces (72 hours post dose) (n=61, 35) | 8.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain (7 days post dose) (n=68, 36) | 16.7 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=61, 35) | 0.0 Percentage of participants |
Secondary
Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab
The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that there is pain, patient states there is pain and winces, and patient states there is pain, winces, and withdraws on palpation or passive movement of the affected study joint; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | No Pain (72 hours post dose) (n=61, 35) | 27.9 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain (72 hours post dose) (n=61, 35) | 54.1 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain and winces (72 hours post dose) (n=61, 35) | 16.4 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=61, 35) | 1.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | No pain (7 days post dose) (n=68, 36) | 52.9 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain (7 days post dose) (n=68, 36) | 44.1 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain and winces (7 days post dose) (n=68, 36) | 2.9 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=61, 36) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=61, 36) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | No Pain (72 hours post dose) (n=61, 35) | 28.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | No pain (7 days post dose) (n=68, 36) | 69.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain (72 hours post dose) (n=61, 35) | 68.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain and winces (7 days post dose) (n=68, 36) | 2.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain and winces (72 hours post dose) (n=61, 35) | 2.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain (7 days post dose) (n=68, 36) | 27.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab | Pain, winces, withdraw(72 hrs post dose)(n=61, 35) | 0.0 Percentage of participants |
Secondary
Physician's Assessment of Range of Motion of the Most Affected Joint
The study physician assessed the range of motion of the most affected joint for range of motion on a 5-point Likert scale: Normal, mildly restricted, moderately restricted, severely restricted, immobilized. The percentage of patients in each category is reported.
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall)
Population: Full Analysis Set (FAS): All patients that received study drug. 'N' in each category indicates participants with observations analyzed for this endpoint at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Normal (Core) [N=113, 111] | 25.7 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Mildly restricted (Core) [N=113, 111] | 50.4 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Moderately restricted (Core) [N=113, 111] | 21.2 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Severely restricted (Core) [N=113, 111] | 2.7 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Immobilized (Core) [N=113, 111] | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Normal (24 weeks) [N=87, 79] | 66.7 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Mildly restricted (24 weeks) [N=87, 79] | 31.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Moderately Restricted (24 weeks) [N=87, 79] | 2.3 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Severely Restricted (24 weeks) [N=87, 79] | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Immobilized (24 weeks) [N=87, 79] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Moderately Restricted (24 weeks) [N=87, 79] | 3.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Normal (Core) [N=113, 111] | 31.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Normal (24 weeks) [N=87, 79] | 65.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Mildly restricted (Core) [N=113, 111] | 29.7 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Immobilized (24 weeks) [N=87, 79] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Moderately restricted (Core) [N=113, 111] | 27.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Mildly restricted (24 weeks) [N=87, 79] | 29.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Severely restricted (Core) [N=113, 111] | 8.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Severely Restricted (24 weeks) [N=87, 79] | 1.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | Immobilized (Core) [N=113, 111] | 3.6 Percentage of participants |
Secondary
Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint
The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that there is pain, patient states there is pain and winces, and patient states there is pain, winces, and withdraws on palpation or passive movement of the affected study joint; Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; and Erythema: Present or absent. The percentage of patients in each category is reported.
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. 'N' in each category indicates participants with observations analyzed for this endpoint at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | TENDERNESS - No pain (Core) [N=113, 110] | 33.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain (Core) [N=113, 110] | 56.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain and winces (Core) [N=113, 110] | 8.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain,winces,withdraws (Core) [N=113,110] | 1.8 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | SWELLING - No swelling (Core) [N=113, 110] | 38.1 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Palpable (Core) [N=113, 110] | 38.9 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Visible (Core) [N=113, 110] | 21.2 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Bulging beyond joint margin (Core) [N=113, 110] | 1.8 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | ERYTHEMA - Absent (Core) [N=112, 109] | 78.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Present (Core) [N=112, 109] | 21.4 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | TENDERNESS - No pain (24 weeks) [N=87, 80] | 82.8 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain (24 weeks) [N=87, 80] | 17.2 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain and winces (24 weeks) [N=87, 80] | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain,winces,withdraws (24 weeks) [N=87, 80] | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | SWELLING - No swelling (24 weeks) [N=87, 80] | 88.5 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Palpable (24 weeks) [N=87, 80] | 8.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Visible (24 weeks) [N=87, 80] | 3.4 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Bulging beyond joint margin (24 week)[N=87,80] | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | ERYTHEMA - Absent (24 weeks) [N=87, 80] | 98.9 Percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Present (24 weeks) [N=87, 80] | 1.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Bulging beyond joint margin (24 week)[N=87,80] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | TENDERNESS - No pain (Core) [N=113, 110] | 26.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | TENDERNESS - No pain (24 weeks) [N=87, 80] | 85.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain (Core) [N=113, 110] | 51.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Palpable (24 weeks) [N=87, 80] | 5.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain and winces (Core) [N=113, 110] | 17.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain (24 weeks) [N=87, 80] | 13.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain,winces,withdraws (Core) [N=113,110] | 4.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Present (24 weeks) [N=87, 80] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | SWELLING - No swelling (Core) [N=113, 110] | 30.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain and winces (24 weeks) [N=87, 80] | 1.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Palpable (Core) [N=113, 110] | 35.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Visible (24 weeks) [N=87, 80] | 1.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Visible (Core) [N=113, 110] | 29.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Pain,winces,withdraws (24 weeks) [N=87, 80] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Bulging beyond joint margin (Core) [N=113, 110] | 5.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | ERYTHEMA - Absent (24 weeks) [N=87, 80] | 100 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | ERYTHEMA - Absent (Core) [N=112, 109] | 65.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | SWELLING - No swelling (24 weeks) [N=87, 80] | 93.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | Present (Core) [N=112, 109] | 34.9 Percentage of participants |
Secondary
Physician's Global Assessment of Response to Treatment
The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity \[Visual Analog Scale and Likert scale\] and patient's global assessment of response to treatment).
Time frame: 72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. 'N' in each category indicates participants with observations analyzed for this endpoint at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Very good (Core) [N=113,110] | 16.8 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Good (Core) [N=113, 110] | 47.8 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Fair (Core) [N= 113, 110] | 26.5 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Poor (Core) [N= 113, 110] | 7.1 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Very poor (Core) [N=113, 110] | 1.8 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Very Good ( 24 weeks) [N=87, 79] | 43.7 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Good (24 weeks) [N=87, 79] | 50.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Fair (24 weeks) [N=87, 79] | 5.7 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Poor (24 weeks) [N=87, 79] | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | Very Poor (24 weeks) [N=87, 79] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Fair (24 weeks) [N=87, 79] | 17.7 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Very good (Core) [N=113,110] | 15.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Very Good ( 24 weeks) [N=87, 79] | 27.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Good (Core) [N=113, 110] | 30.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Very Poor (24 weeks) [N=87, 79] | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Fair (Core) [N= 113, 110] | 32.7 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Good (24 weeks) [N=87, 79] | 50.6 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Poor (Core) [N= 113, 110] | 14.5 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Poor (24 weeks) [N=87, 79] | 3.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | Very poor (Core) [N=113, 110] | 7.3 Percentage of participants |
Secondary
Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab
The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity \[Visual Analog Scale and Likert scale\] and patient's global assessment of response to treatment). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 72 hours post-dose , 7 days post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very good (72 hours post dose) (n=61, 34) | 21.3 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (72 hours post dose) (n=61, 34) | 41.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Fair (72 hours post dose) (n=61, 34) | 31.1 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (72 hours post dose) (n=61, 34) | 6.6 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very poor (72 hours post dose) (n=61, 34) | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very Good (7 days post dose) (n=68, 34) | 36.8 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (7 days post dose) (n=68, 34) | 52.9 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Fair (7 days post dose) (n=68, 34) | 10.3 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (7 days post dose) (n=68, 34) | 0.0 Percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very Poor (7 days post dose) (n=68, 34) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Fair (7 days post dose) (n=68, 34) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very good (72 hours post dose) (n=61, 34) | 22.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very Good (7 days post dose) (n=68, 34) | 33.3 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (72 hours post dose) (n=61, 34) | 57.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very Poor (7 days post dose) (n=68, 34) | 2.8 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Fair (72 hours post dose) (n=61, 34) | 17.1 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Good (7 days post dose) (n=68, 34) | 63.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (72 hours post dose) (n=61, 34) | 2.9 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Poor (7 days post dose) (n=68, 34) | 0.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab | Very poor (72 hours post dose) (n=61, 34) | 0.0 Percentage of participants |
Secondary
Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab
Serum Amyloid A Protein (SAA) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.
Time frame: 24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)
Population: Modified Analysis Set (MAS) consists of all FAS patients who were either re-treated or switched to canakinumab during 72 weeks. At each timepoint only patients with a value at both baseline flare and the new flare are included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 24 hours post dose (n= 45, 27) | 151.4 mg/L | Standard Deviation 310.09 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 72 hours post dose (n=45, 36) | 42.5 mg/L | Standard Deviation 116.89 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 7 days post dose (n=67, 39) | 5.4 mg/L | Standard Deviation 8.83 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 4 weeks post dose (n=52, 35) | 31.0 mg/L | Standard Deviation 193.64 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 8 weeks post dose (n=45, 37) | 4.2 mg/L | Standard Deviation 4.26 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 12 weeks post dose (n=42, 33) | 10.7 mg/L | Standard Deviation 24.62 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 8 weeks post dose (n=45, 37) | 5.4 mg/L | Standard Deviation 8.36 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 24 hours post dose (n= 45, 27) | 86.5 mg/L | Standard Deviation 188.46 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 4 weeks post dose (n=52, 35) | 8.5 mg/L | Standard Deviation 19.75 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 72 hours post dose (n=45, 36) | 26.9 mg/L | Standard Deviation 73.37 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 12 weeks post dose (n=42, 33) | 7.8 mg/L | Standard Deviation 22.98 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab | 7 days post dose (n=67, 39) | 4.9 mg/L | Standard Deviation 6.56 |
Secondary
SF36 Physical Function Score at Week 12
The SF-36 measures the impact of disease on overall quality of life (QoL). This 36-item survey has 8 subscales that can be aggregated into physical- and mental-component summary scores. Scores are standardized with the use of norm-based methods based on an assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL. A negative change score indicates improvement. An ANCOVA model was used with treatment group and baseline SF-36 physical function subscore as covariates.
Time frame: Week 12
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. Participant observations at Week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | SF36 Physical Function Score at Week 12 | 71.76 Units on a scale | Standard Error 2.688 |
| Triamcinolone Acetonide 40 mg | SF36 Physical Function Score at Week 12 | 71.48 Units on a scale | Standard Error 2.745 |
Secondary
Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS)
The Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at baseline was determined along with the 95% confidence interval. Patients scored their pain intensity on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose.
Time frame: From baseline to 7 days post dose (randomization)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. Last Observation Carried Forward (LOCF) method was used to impute post dose measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab 150 mg | Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) | 48.0 Hours |
| Triamcinolone Acetonide 40 mg | Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS) | 72.0 Hours |
Secondary
Time to Complete Resolution of Pain
Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose. The Kaplan-Meier estimates of time to complete resolution of self-assessed pain intensity in the joint most affected and their confidence intervals were determined.
Time frame: 7 days post-dose (randomization)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab 150 mg | Time to Complete Resolution of Pain | NA Hours |
| Triamcinolone Acetonide 40 mg | Time to Complete Resolution of Pain | NA Hours |
Secondary
Time to First Intake of Rescue Medication After the Last Post Baseline Flare.
The Kaplan-Meier estimates of medians and 95% confidence intervals were used to calculate the endpoint.
Time frame: 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug. Patients with observations 72 hours post-dose for the last post-baseline flare during 24 weeks were included in analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab 150 mg | Time to First Intake of Rescue Medication After the Last Post Baseline Flare. | NA Hours |
| Triamcinolone Acetonide 40 mg | Time to First Intake of Rescue Medication After the Last Post Baseline Flare. | NA Hours |
Secondary
Time to First New Flare
Kaplan-Meier (KM) estimates of time to first new flare and confidence intervals were determined. Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
Time frame: 24 weeks
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab 150 mg | Time to First New Flare | NA Days |
| Triamcinolone Acetonide 40 mg | Time to First New Flare | 119 Days |
Secondary
Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall)
Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: * Flare in joint, not a previously affected joint (at baseline or during study) * Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before flare has resolved completely.
Time frame: 72 weeks overall
Population: The Full Analysis Set (FAS) consisted of all patients as randomized in the core study who had taken at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab 150 mg | Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall) | 222.0 days |
| Triamcinolone Acetonide 40 mg | Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall) | 119.0 days |