Acute Gout
Conditions
Keywords
Frequent flares, Gout, Anti-interleukin-1β monoclonal antibody
Brief summary
The purpose of this 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 CACZ885H2357. The purpose of the second one year open-label extension study was to confirm the long-term safety and tolerability of canakinumab in patients who had completed the first extension study.
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, or intolerance, or lack of efficacy for non-steroidal anti-inflammatory drugs (NSAID) 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 Criteria: * Completion of the first extension study CACZ885H2357E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First New Flare: Survival Analysis During the 12 Weeks of Study | Baseline to 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 (VAS) at 72 Hours Post-dose | 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 analysis of covariance (ANCOVA) analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates. |
| Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks | During 24 weeks overall | This was primary endpoint of extension study 1. 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. A 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, Death and Serious Adverse Events (72 Weeks Overall) | 72 weeks | This was the primary endpoint of extension study 2. An adverse event was 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 |
|---|---|---|
| Pharmacokinetic Concentrations | 12 weeks post-dose | Canakinumab concentration was analyzed in serum by means of a competitive Enzyme-linked immunosorbent assay (ELISA) assay with a lower limit of quantification (LOQ) at 100 ng/mL. |
| Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days 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), from 6 hours to 7 days 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. |
| Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose for last post-baseline flare that occurred up until the end of the first extension study (24 weeks). | Patient's assessment of gout pain intensity in the most affected joint (on a 0-100 mm VAS) for the last post-baseline flare, ranging from no pain (0) to unbearable pain (100), was summarized up to 7 days after receiving a re-dose of study drug by time point. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The covariance analysis included treatment group, Baseline VAS score at that flare, and body mass index (BMI) at Baseline as covariates. |
| Time to the First New Gout Flare During 24 Weeks | From randomization to the end of the first extension period (24 weeks). | Kaplan-Meier (KM) estimates of the time to first new flare and confidence intervals were determined. Participants met the definition of a 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. Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely. |
| Mean Number of New Gout Flares Per Patient During 24 Weeks | 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. Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely. |
| Time to First Intake of Rescue Medication | For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). | Participants 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, participants were allowed to take a maximum of 30 mg of oral prednisolone 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. Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication. Kaplan-Meier estimates of the time to first intake of rescue medication, in hours, and the confidence interval were determined for the flare experienced at study entry (Baseline flare) and the last new flare (last post-baseline flare) that occurred up until the end of the first extension period (24 weeks). |
| Percentage of Participants Who Took Rescue Medication | For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). | Participants 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, participants were allowed to take a maximum of 30 mg of oral prednisolone 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. Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication. |
| Amount of Rescue Medication Taken | For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (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 prednisolone 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. |
| Physician's Global Assessment of Response to Treatment | 72 hours post-dose and 24-weeks post-dose. | 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 own assessments (pain intensity and patient's global assessment of response to treatment). |
| Patient's Global Assessment of Response to Treatment | 72 hours post-dose and 24 weeks post-dose | Participants made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. The percentage of participants in each category is reported. |
| Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours post-dose and 24 weeks post-dose | 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 participants in each category is reported. |
| Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours post-dose and 24 weeks post-dose | 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 participants in each category is reported. |
| 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 (VAS) | Baseline to 7 days post-dose (randomization) | Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at Baseline and the confidence intervals were determined along with 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. |
| Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours post-dose and 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). |
| Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme | From the onset of a new flare until re-dosing. First post-baseline new flare during 12 week core study and the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). | For each new flare, participants scored the maximum amount of acute gout pain in the most affected joint since the onset of the new flare and the time they were re-dosed on a 5 point Likert scale as None, Mild, Moderate, Severe or Extreme. The percentage of participants with a maximum new flare severity of severe or extreme is reported for the first post-baseline flare that occurred during the 12-week core study and for the last post-baseline flare that occurred up until the end of the first extension period. |
| Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks | From randomization to the end of the second extension period (72 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. |
| Flare Rate Per Year | From randomization to the end of the second extension period (72 weeks). | 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. Participants met the 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. Participants did not meet criterion of having new gout flare if: • Increasing/renewed gout pain in an affected joint before the flare has resolved completely. Flare rates were estimated from a negative binomial model with body mass index at baseline as a covariate. |
| Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | Participants scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe or extreme). Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | Participants made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight or poor. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | 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 or very poor. The physician completed the physician's global assessment of response to treatment without viewing any of the patient's assessments. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | The study physician assessed the most affected joint for tenderness on the following 4-point scale: * no pain; * participant states that there is pain; * participant states there is pain and winces; * participant states there is pain, winces and withdraws on palpation or passive movement of the affected study joint. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | The study physician assessed the most affected joint for swelling on the following 4-point scale: * no swelling; * palpable; * visible; * bulging beyond the joint margins. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | The study physician assessed the most affected joint for erythema (redness of the skin) as either present, absent or not assessable. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | High sensitivity C-reactive protein (hsCRP) levels in blood serum were measured by a central laboratory in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. | Serum Amyloid A Protein (SAA) levels in blood serum were measured by a central laboratory in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2. |
| High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | 72 hours after the first dose for the baseline flare and 72 hours post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). | 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. Analyses 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 to Complete Resolution of Pain; Survival Analysis | Baseline to 7 days post-dose (randomization) | Kaplan-Meier estimates of the time to complete resolution of self-assessed pain intensity in the joint most affected and the confidence interval was determined. Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Pain was scored at Baseline; 6 and 12 hours; 1, 2, 3, 4, 5, 6, and 7 days post-dose. |
| SF 36 Physical Function Score at Week 12 | Week 12 | SF-36 measures impact of disease on overall quality of life (QoL). 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 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. Analysis of covariance (ANCOVA) model was used with treatment group and baseline SF-36 physical function subscore as covariates. |
| Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study | Baseline to Week 12 | The percentage of participants who experienced at least 1 new gout flare during the 12 week study treatment period. |
Countries
Canada, China, Netherlands, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab 150 mg Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants 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. In the first extension study participants completing the 12 week core study could continue to be treated on demand with the same treatment for another 12 weeks for any new gout flare.
In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc for any new flare for an additional year, for a total duration of 18 months. | 112 |
| Triamcinolone Acetonide 40 mg Participants received 1 intramuscular injection of triamcinolone acetonide 40 mg and 1 sc injection of placebo to canakinumab on Day 1. Participants 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.
In the first extension study participants completing the 12 week core study could continue to be treated on demand with the same treatment for another 12 weeks for any new gout flare.
In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc for any new flare for an additional year. Triamcinolone acetonide was not to be administered in the second extension study. | 114 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Study (0- 12 Weeks) | Abnormal laboratory value(s) | 1 | 1 |
| Core Study (0- 12 Weeks) | Administrative problems | 0 | 1 |
| Core Study (0- 12 Weeks) | Death | 1 | 0 |
| Core Study (0- 12 Weeks) | Lost to Follow-up | 5 | 3 |
| Core Study (0- 12 Weeks) | Patient withdrew consent | 6 | 4 |
| Core Study (0- 12 Weeks) | Protocol deviation | 0 | 2 |
| Extension Study 1 (12 -24 Weeks) | Adverse Event | 1 | 0 |
| Extension Study 1 (12 -24 Weeks) | Lost to Follow-up | 1 | 0 |
| Extension Study 1 (12 -24 Weeks) | Unsatisfactory Therapeutic Effect | 0 | 1 |
| Extension Study 1 (12 -24 Weeks) | Withdrawal by Subject | 4 | 3 |
| Extension Study 2 (25-72 Weeks) | Adverse Event | 1 | 2 |
| Extension Study 2 (25-72 Weeks) | Lost to Follow-up | 4 | 5 |
| Extension Study 2 (25-72 Weeks) | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Canakinumab 150 mg | Triamcinolone Acetonide 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 50.6 years STANDARD_DEVIATION 12.1 | 52.6 years STANDARD_DEVIATION 12.28 | 51.6 years STANDARD_DEVIATION 12.21 |
| Sex: Female, Male Female | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Male | 100 Participants | 105 Participants | 205 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 | 42 / 112 | 15 / 62 | 19 / 62 | 36 / 114 | 15 / 41 | 8 / 41 |
| serious Total, serious adverse events | 12 / 112 | 1 / 62 | 5 / 62 | 4 / 114 | 0 / 41 | 3 / 41 |
Outcome results
Primary
Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall)
This was the primary endpoint of extension study 2. An adverse event was 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
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, Death and Serious Adverse Events (72 Weeks Overall) | Death | 1 participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Any adverse event | 85 participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Serious adverse event | 12 participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Any adverse event | 44 participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Serious adverse event | 1 participants |
| Canakinumab: After Retreatment | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 participants |
| Canakinumab: After Retreatment | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Any adverse event | 39 participants |
| Canakinumab: After Retreatment | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Serious adverse event | 5 participants |
| All Triamcinolone Acetonide | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 participants |
| All Triamcinolone Acetonide | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Any adverse event | 70 participants |
| All Triamcinolone Acetonide | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Serious adverse event | 4 participants |
| Triam: Before Switch to Canakinumab | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 participants |
| Triam: Before Switch to Canakinumab | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Any adverse event | 29 participants |
| Triam: Before Switch to Canakinumab | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Serious adverse event | 0 participants |
| Triam: After Switch to Canakinumab | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Any adverse event | 27 participants |
| Triam: After Switch to Canakinumab | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Serious adverse event | 3 participants |
| Triam: After Switch to Canakinumab | Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) | Death | 0 participants |
Primary
Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks
This was primary endpoint of extension study 1. 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. A 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: During 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, Death and Serious Adverse Events During 24 Weeks | Adverse event | 78 Participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks | Death | 1 Participants |
| Canakinumab 150 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks | Serious adverse event | 7 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks | Adverse event | 65 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks | Death | 0 Participants |
| Triamcinolone Acetonide 40 mg | Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks | Serious adverse event | 2 Participants |
Primary
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose
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 analysis of covariance (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: 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 (VAS) at 72 Hours Post-dose | 22.1 mm | Standard Error 2.33 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose | 31.9 mm | Standard Error 2.35 |
Primary
Time to First New Flare: Survival Analysis During the 12 Weeks of Study
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: Baseline to 12 weeks
Population: 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 During the 12 Weeks of Study | NA Days |
| Triamcinolone Acetonide 40 mg | Time to First New Flare: Survival Analysis During the 12 Weeks of Study | 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 prednisolone 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: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
Population: For the Baseline flare the population analyzed consisted of the Full Analysis Set (FAS). For the last post-baseline flare the population analyzed consisted of patients re-treated for at least one new flare.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Baseline flare: Acetaminophen [N=112, 114] | 1375.0 mg | Standard Deviation 2726.63 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Baseline flare: Codeine [N=112, 114] | 27.2 mg | Standard Deviation 100.4 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Baseline flare: Prednisone/Predinisone [N=112,114] | 9.2 mg | Standard Deviation 35.32 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Last flare: Acetaminophen [N=25, 46] | 2292.0 mg | Standard Deviation 3462.65 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Last flare: Codeine [N= 25, 46] | 64.8 mg | Standard Deviation 224.11 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken | Last flare: Prednisolone/Predinisone [N= 25, 46] | 5.6 mg | Standard Deviation 14.46 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Last flare: Codeine [N= 25, 46] | 65.2 mg | Standard Deviation 178.7 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Baseline flare: Acetaminophen [N=112, 114] | 2526.5 mg | Standard Deviation 3925.13 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Last flare: Acetaminophen [N=25, 46] | 1541.3 mg | Standard Deviation 3771.33 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Baseline flare: Codeine [N=112, 114] | 60.6 mg | Standard Deviation 144.38 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Last flare: Prednisolone/Predinisone [N= 25, 46] | 18.3 mg | Standard Deviation 48 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken | Baseline flare: Prednisone/Predinisone [N=112,114] | 19.3 mg | Standard Deviation 44.88 |
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. Participants met the 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. Participants did not meet criterion of having new gout flare if: • Increasing/renewed gout pain in an affected joint before the flare has resolved completely. Flare rates were estimated from a negative binomial model with body mass index at baseline as a covariate.
Time frame: From randomization to the end of the second extension period (72 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) |
|---|---|---|
| Canakinumab 150 mg | Flare Rate Per Year | 1.18 flares per patient per year |
| Triamcinolone Acetonide 40 mg | Flare Rate Per Year | 2.02 flares per patient per year |
Secondary
High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels
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. Analyses 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 after the first dose for the baseline flare and 72 hours post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
Population: For the Baseline flare the population analyzed consisted of the Full Analysis Set (FAS). For the last post-baseline flare the population analyzed consisted of patients re-treated for at least one new flare. N indicates the number of participants with available data in each analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Baseline flare: hsCRP [N=107, 110] | 3.84 mg/L |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Baseline flare: SAA [N=95, 104] | 6.31 mg/L |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Last post-baseline flare: hsCRP [N= 22, 42] | 3.69 mg/L |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Last post-baseline flare: SAA, [N= 19, 39] | 6.74 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Last post-baseline flare: SAA, [N= 19, 39] | 11.04 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Baseline flare: hsCRP [N=107, 110] | 6.38 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Last post-baseline flare: hsCRP [N= 22, 42] | 4.32 mg/L |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels | Baseline flare: SAA [N=95, 104] | 15.85 mg/L |
Secondary
High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab
High sensitivity C-reactive protein (hsCRP) levels in blood serum were measured by a central laboratory in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 Participants Re-treated With or Switched to Canakinumab | 24-hours post-dose [N=48, 36] | 30.1 mg/L | Standard Deviation 64.11 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 72-hours post-dose [N=56, 38] | 10.4 mg/L | Standard Deviation 31.11 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 7 days post-dose [N=55, 40] | 2.8 mg/L | Standard Deviation 4.97 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 4 weeks post-dose [N=46, 37] | 1.6 mg/L | Standard Deviation 2.3 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 8 weeks post-dose [N=37, 35] | 2.1 mg/L | Standard Deviation 4.41 |
| Canakinumab 150 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 12 weeks post-dose [N=38, 31] | 1.3 mg/L | Standard Deviation 0.79 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 8 weeks post-dose [N=37, 35] | 2.4 mg/L | Standard Deviation 4.62 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 24-hours post-dose [N=48, 36] | 39.4 mg/L | Standard Deviation 41.1 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 4 weeks post-dose [N=46, 37] | 2.2 mg/L | Standard Deviation 3.54 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 72-hours post-dose [N=56, 38] | 12.6 mg/L | Standard Deviation 15.8 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 12 weeks post-dose [N=38, 31] | 2.9 mg/L | Standard Deviation 4.9 |
| Triamcinolone Acetonide 40 mg | High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab | 7 days post-dose [N=55, 40] | 3.5 mg/L | Standard Deviation 5 |
Secondary
Mean Number of New Gout Flares Per Patient During 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. Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.
Time frame: 24 weeks
Population: 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 24 Weeks | 0.35 new flares per patient | Standard Deviation 0.694 |
| Triamcinolone Acetonide 40 mg | Mean Number of New Gout Flares Per Patient During 24 Weeks | 0.80 new flares per patient | Standard Deviation 1.115 |
Secondary
Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab
Participants scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe or extreme). Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 for Participants Re-treated or Switched to Canakinumab | 7 days - None [N=57, 37] | 64.9 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Moderate [N=59, 40] | 22.0 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Mild [N=57, 37] | 21.1 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Mild [N=59, 40] | 44.1 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Moderate [N=57, 37] | 10.5 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Severe [N=59, 40] | 3.4 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Severe [N=57, 37] | 3.5 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - None [N=59, 40] | 30.5 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Extreme [N=57, 37] | 0.0 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Extreme [N=59, 40] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Extreme [N=57, 37] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - None [N=59, 40] | 25.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Mild [N=59, 40] | 62.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Moderate [N=59, 40] | 12.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Severe [N=59, 40] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - None [N=57, 37] | 59.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Mild [N=57, 37] | 35.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Moderate [N=57, 37] | 5.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 7 days - Severe [N=57, 37] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab | 72 hours - Extreme [N=59, 40] | 0.0 percentage of participants |
Secondary
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint
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).
Time frame: 72 hours post-dose and 24 weeks post-dose
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 available at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Extreme [N=108, 111] | 0.0 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - None [N=108, 111] | 30.6 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - None [N=79, 70] | 72.2 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Moderate [N=108, 111] | 20.4 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Mild [N=79, 70] | 19.0 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Severe [N=79, 70] | 2.5 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Moderate [N=79, 70] | 6.3 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Severe [N=108, 111] | 0.9 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Extreme [N=79, 70] | 0.0 percentage of participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Mild [N=108, 111] | 48.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Extreme [N=79, 70] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - None [N=108, 111] | 18.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Mild [N=108, 111] | 45.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Moderate [N=108, 111] | 27.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Severe [N=108, 111] | 8.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 72 hours - Extreme [N=108, 111] | 1.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - None [N=79, 70] | 67.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Mild [N=79, 70] | 25.7 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Severe [N=79, 70] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | 24 weeks - Moderate [N=79, 70] | 7.1 percentage of participants |
Secondary
Patient's Global Assessment of Response to Treatment
Participants made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. The percentage of participants in each category is reported.
Time frame: 72 hours post-dose and 24 weeks post-dose
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 available at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Acceptable [N=108, 108] | 18.5 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Excellent [N=79, 72] | 59.5 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Good [N=108, 108] | 37.0 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Good [N=79, 72] | 26.6 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Slight [N=108, 108] | 4.6 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Acceptable [N=79, 72] | 6.3 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Excellent [N=108, 108] | 36.1 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Poor [N=108, 108] | 3.7 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Poor [N=79, 72] | 1.3 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Slight [N=79, 72] | 6.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Poor [N=79, 72] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Excellent [N=108, 108] | 19.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Good [N=108, 108] | 32.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Acceptable [N=108, 108] | 13.9 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Slight [N=108, 108] | 25.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 72 hours - Poor [N=108, 108] | 9.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Excellent [N=79, 72] | 40.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Good [N=79, 72] | 44.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Acceptable [N=79, 72] | 13.9 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment | 24 weeks - Slight [N=79, 72] | 1.4 percentage of participants |
Secondary
Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab
Participants made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight or poor. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 Participants Re-treated or Switched to Canakinumab | 72 hours - Excellent [N=58, 38] | 41.4 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Poor [N=56, 39] | 3.6 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Good [N=58, 38] | 32.8 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Acceptable [N=58, 38] | 12.1 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Slight [N=58, 38] | 13.8 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Poor [N=58, 38] | 0.0 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Excellent [N=56, 39] | 51.8 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Good [N=56, 39] | 26.8 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Acceptable [N=56, 39] | 10.7 percentage of participants |
| Canakinumab 150 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Slight [N=56, 39] | 7.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Good [N=56, 39] | 33.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Poor [N=58, 38] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Poor [N=56, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Excellent [N=58, 38] | 36.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Slight [N=56, 39] | 7.7 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Good [N=58, 38] | 39.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Excellent [N=56, 39] | 51.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Acceptable [N=58, 38] | 21.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Acceptable [N=56, 39] | 7.7 percentage of participants |
| Triamcinolone Acetonide 40 mg | Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Slight [N=58, 38] | 2.6 percentage of participants |
Secondary
Percentage of Participants Who Took Rescue Medication
Participants 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, participants were allowed to take a maximum of 30 mg of oral prednisolone 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. Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication.
Time frame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
Population: For the Baseline flare the population analyzed consisted of the Full Analysis Set (FAS). For the last post-baseline flare the population analyzed consisted of patients re-treated for at least one new flare.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Percentage of Participants Who Took Rescue Medication | Baseline flare [N= 112, 114] | 43.8 percentage of participants |
| Canakinumab 150 mg | Percentage of Participants Who Took Rescue Medication | Last post-baseline flare [N=25, 46] | 56.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants Who Took Rescue Medication | Last post-baseline flare [N=25, 46] | 41.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants Who Took Rescue Medication | Baseline flare [N= 112, 114] | 57.0 percentage of participants |
Secondary
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study
The percentage of participants who experienced at least 1 new gout flare during the 12 week study treatment period.
Time frame: Baseline to Week 12
Population: 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 of the Study | 13.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study | 36.8 percentage of participants |
Secondary
Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme
For each new flare, participants scored the maximum amount of acute gout pain in the most affected joint since the onset of the new flare and the time they were re-dosed on a 5 point Likert scale as None, Mild, Moderate, Severe or Extreme. The percentage of participants with a maximum new flare severity of severe or extreme is reported for the first post-baseline flare that occurred during the 12-week core study and for the last post-baseline flare that occurred up until the end of the first extension period.
Time frame: From the onset of a new flare until re-dosing. First post-baseline new flare during 12 week core study and the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
Population: The number of participants analyzed (indicated by 'N') for the first new post-baseline flare includes patients who were re-treated for a new flare during the 12-week core study. For the last post-baseline flare the population analyzed includes patients re-treated for at least one new flare during the first 24 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme | First post-baseline flare [N= 12, 37] | 66.7 Percentage of participants |
| Canakinumab 150 mg | Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme | Last post-baseline flare [N= 25, 46] | 64.0 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme | First post-baseline flare [N= 12, 37] | 78.4 Percentage of participants |
| Triamcinolone Acetonide 40 mg | Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme | Last post-baseline flare [N= 25, 46] | 78.3 Percentage of participants |
Secondary
Pharmacokinetic Concentrations
Canakinumab concentration was analyzed in serum by means of a competitive Enzyme-linked immunosorbent assay (ELISA) assay with a lower limit of quantification (LOQ) at 100 ng/mL.
Time frame: 12 weeks post-dose
Population: 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 | Pharmacokinetic Concentrations | 2.16 µg/mL | Standard Deviation 2.375 |
Secondary
Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab
The study physician assessed the most affected joint for erythema (redness of the skin) as either present, absent or not assessable. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 Participants Re-treated or Switched to Canakinumab | 72 hours - Present [N=56, 38] | 26.8 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 72 hours - Absent [N=56, 38] | 73.2 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 7 days - Absent [N=58, 39] | 84.5 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 7 days - Present [N=58, 39] | 15.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 7 days - Present [N=58, 39] | 5.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 7 days - Absent [N=58, 39] | 94.9 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 72 hours - Absent [N=56, 38] | 92.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab | 72 hours - Present [N=56, 38] | 7.9 percentage of participants |
Secondary
Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab
The study physician assessed the most affected joint for swelling on the following 4-point scale: * no swelling; * palpable; * visible; * bulging beyond the joint margins. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 Participants Re-treated or Switched to Canakinumab | 72 hours - No swelling [N=56, 38] | 55.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours - Palpable [N=56, 38] | 26.8 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours - Visible [N=56, 38] | 12.5 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours - Bulging beyond joint margins [N=56, 38] | 5.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - No swelling [N=58, 39] | 70.7 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - Palpable [N=58, 39] | 17.2 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - Visible [N=58, 39] | 10.3 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - Bulging beyond joint margins [N=58, 39] | 1.7 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - Bulging beyond joint margins [N=58, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours - No swelling [N=56, 38] | 47.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - No swelling [N=58, 39] | 79.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours - Palpable [N=56, 38] | 34.2 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - Visible [N=58, 39] | 2.6 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours - Visible [N=56, 38] | 15.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 7 days - Palpable [N=58, 39] | 17.9 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab | 72 hours - Bulging beyond joint margins [N=56, 38] | 2.6 percentage of participants |
Secondary
Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab
The study physician assessed the most affected joint for tenderness on the following 4-point scale: * no pain; * participant states that there is pain; * participant states there is pain and winces; * participant states there is pain, winces and withdraws on palpation or passive movement of the affected study joint. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 Participants Re-treated or Switched to Canakinumab | 72 hours - No pain [N=56, 38] | 51.8 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours - Pain [N=56, 38] | 37.5 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours - Pain and winces [N=56, 38] | 5.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours - Pain, winces and withdraws [N=56, 38] | 5.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - No pain [N=58, 39] | 74.1 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - Pain [N=58, 39] | 22.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - Pain and winces [N=58, 39] | 3.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - Pain, winces and withdraws [N=58, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - Pain, winces and withdraws [N=58, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours - No pain [N=56, 38] | 42.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - No pain [N=58, 39] | 79.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours - Pain [N=56, 38] | 50.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - Pain and winces [N=58, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours - Pain and winces [N=56, 38] | 5.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 7 days - Pain [N=58, 39] | 20.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab | 72 hours - Pain, winces and withdraws [N=56, 38] | 2.6 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 participants in each category is reported.
Time frame: 72 hours post-dose and 24 weeks post-dose
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 available at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Normal [N=107,109] | 47.7 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Mildly restricted [N=107,109] | 37.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Moderately restricted [N=107,109] | 13.1 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Severely restricted [N=107,109] | 1.9 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Immobilized [N=107,109] | 0.0 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Normal [N=79, 71] | 86.1 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Mildly restricted [N=79, 71] | 10.1 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Moderately restricted [N=79, 71] | 2.5 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Severely restricted [N=79, 71] | 1.3 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Immobilized [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Moderately restricted [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Normal [N=107,109] | 28.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Normal [N=79, 71] | 97.2 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Mildly restricted [N=107,109] | 45.9 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Immobilized [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Moderately restricted [N=107,109] | 20.2 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Mildly restricted [N=79, 71] | 2.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Severely restricted [N=107,109] | 5.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 24 weeks - Severely restricted [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Range of Motion of the Most Affected Joint | 72 hours - Immobilized [N=107,109] | 0.0 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 participants in each category is reported.
Time frame: 72 hours post-dose and 24 weeks post-dose
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 available at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness: No pain [N=107, 109] | 47.7 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness: Pain [N=107, 109] | 43.9 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness: Pain & winces [N=107, 109] | 4.7 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness:Winces/withdraws [N=107,109] | 3.7 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: No pain [N=79, 71] | 88.6 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: Pain [N=79, 71] | 8.9 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: Pain and winces [N=79, 71] | 1.3 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: Winces/withdraws [N=79, 71] | 1.3 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: No swelling [N=107,109] | 47.7 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: Palpable [N=107,109] | 28.0 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: Visible [N=107,109] | 22.4 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: Bulging [N=107,109] | 1.9 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: No swelling [N=79, 71] | 93.7 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: Palpable [N=79, 71] | 5.1 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: Visible [N=79, 71] | 1.3 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: Bulging [N=79, 71] | 0.0 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Erythema: Absent [N=107, 108] | 74.8 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Erythema: Present [N=107, 108] | 25.2 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Erythema: Absent [N=79, 71] | 97.5 percentage of participants |
| Canakinumab 150 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Erythema: Present [N=79, 71] | 2.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Erythema: Present [N=107, 108] | 33.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness: No pain [N=107, 109] | 30.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: Visible [N=107,109] | 28.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness: Pain [N=107, 109] | 46.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: Bulging [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness: Pain & winces [N=107, 109] | 14.7 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: Bulging [N=107,109] | 6.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Tenderness:Winces/withdraws [N=107,109] | 8.3 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Erythema: Present [N=79, 71] | 2.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: No pain [N=79, 71] | 91.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: No swelling [N=79, 71] | 94.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: Pain [N=79, 71] | 5.6 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Erythema: Absent [N=107, 108] | 66.7 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: Pain and winces [N=79, 71] | 1.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: Palpable [N=79, 71] | 4.2 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Tenderness: Winces/withdraws [N=79, 71] | 1.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Erythema: Absent [N=79, 71] | 97.2 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: No swelling [N=107,109] | 35.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 24 weeks - Swelling: Visible [N=79, 71] | 1.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint | 72 hours - Swelling: Palpable [N=107,109] | 29.4 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 own assessments (pain intensity and patient's global assessment of response to treatment).
Time frame: 72 hours post-dose and 24-weeks post-dose.
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 available for this endpoint at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Very good [N= 107, 109] | 43.0 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Good [N= 107, 109] | 43.0 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Fair [N= 107, 109] | 11.2 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Poor [N= 107, 109] | 2.8 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Very poor [N= 107, 109] | 0.0 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Very good [N=79, 71] | 77.2 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Good [N=79, 71] | 16.5 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Fair [N=79, 71] | 5.1 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Poor [N=79, 71] | 1.3 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Very poor [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Fair [N=79, 71] | 4.2 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Very good [N= 107, 109] | 25.7 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Very good [N=79, 71] | 66.2 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Good [N= 107, 109] | 35.8 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Very poor [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Fair [N= 107, 109] | 26.6 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Good [N=79, 71] | 29.6 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Poor [N= 107, 109] | 6.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 24 weeks - Poor [N=79, 71] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment | 72 hours - Very poor [N= 107, 109] | 5.5 percentage of participants |
Secondary
Physician's Global Assessment of Response to Treatment for Participants 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 or very poor. The physician completed the physician's global assessment of response to treatment without viewing any of the patient's assessments. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 Participants Re-treated or Switched to Canakinumab | 72 hours - Very good [N=56, 38] | 39.3 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Good [N=56, 38] | 39.3 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Fair [N=56, 38] | 16.1 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Poor [N=56, 38] | 5.4 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Very poor [N=56, 38] | 0.0 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Very good [N=58, 39] | 56.9 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Good [N=58, 39] | 25.9 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Fair [N=58, 39] | 15.5 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Poor [N=58, 39] | 1.7 percentage of participants |
| Canakinumab 150 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Very poor [N=58, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Fair [N=58, 39] | 2.6 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Very good [N=56, 38] | 42.1 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Very good [N=58, 39] | 59.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Good [N=56, 38] | 39.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Very poor [N=58, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Fair [N=56, 38] | 18.4 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Good [N=58, 39] | 38.5 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Poor [N=56, 38] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 7 days - Poor [N=58, 39] | 0.0 percentage of participants |
| Triamcinolone Acetonide 40 mg | Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab | 72 hours - Very poor [N=56, 38] | 0.0 percentage of participants |
Secondary
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm 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), from 6 hours to 7 days 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: 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose (randomization)
Population: 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 | Group | 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 (0-100 mm VAS) | 12 hours post-dose | 50.8 mm | Standard Error 2.16 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 4 days post-dose | 19.2 mm | Standard Error 2.25 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 48 hours post-dose | 29.5 mm | Standard Error 2.45 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 5 days post-dose | 16.4 mm | Standard Error 2.23 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 24 hours post-dose | 39.1 mm | Standard Error 2.39 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 6 days post-dose | 14.3 mm | Standard Error 2.2 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 72 hours post-dose | 22.1 mm | Standard Error 2.33 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 7 days post-dose | 14.0 mm | Standard Error 2.18 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 6 hours post-dose | 58.7 mm | Standard Error 1.94 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 7 days post-dose | 19.5 mm | Standard Error 2.2 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 6 hours post-dose | 60.3 mm | Standard Error 1.96 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 12 hours post-dose | 52.0 mm | Standard Error 2.18 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 24 hours post-dose | 45.0 mm | Standard Error 2.41 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 48 hours post-dose | 38.9 mm | Standard Error 2.48 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 72 hours post-dose | 31.9 mm | Standard Error 2.35 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 4 days post-dose | 27.7 mm | Standard Error 2.27 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 5 days post-dose | 25.4 mm | Standard Error 2.25 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) | 6 days post-dose | 22.3 mm | Standard Error 2.22 |
Secondary
Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS)
Patient's assessment of gout pain intensity in the most affected joint (on a 0-100 mm VAS) for the last post-baseline flare, ranging from no pain (0) to unbearable pain (100), was summarized up to 7 days after receiving a re-dose of study drug by time point. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The covariance analysis included treatment group, Baseline VAS score at that flare, and body mass index (BMI) at Baseline as covariates.
Time frame: 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose for last post-baseline flare that occurred up until the end of the first extension study (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. For assessments made up to 7 days after re-dosing, pain values were imputed using the Last- Observation-Carried-Forward (LOCF) method.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 12 hours post-dose | 50.7 mm | Standard Error 4.24 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 4 days post-dose | 31.3 mm | Standard Error 4.75 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 48 hours post-dose | 42.3 mm | Standard Error 4.96 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 5 days post-dose | 29.0 mm | Standard Error 5.11 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 24 hours post-dose | 46.2 mm | Standard Error 4.74 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 6 days post-dose | 28.1 mm | Standard Error 5.04 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 72 hours post-dose | 37.0 mm | Standard Error 5.12 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 7 days post-dose | 24.1 mm | Standard Error 5.03 |
| Canakinumab 150 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 6 hours post-dose | 57.4 mm | Standard Error 3.07 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 7 days post-dose | 19.1 mm | Standard Error 3.7 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 6 hours post-dose | 59.1 mm | Standard Error 2.26 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 12 hours post-dose | 53.3 mm | Standard Error 3.12 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 24 hours post-dose | 43.8 mm | Standard Error 3.49 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 48 hours post-dose | 34.2 mm | Standard Error 3.65 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 72 hours post-dose | 26.1 mm | Standard Error 3.77 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 4 days post-dose | 23.4 mm | Standard Error 3.49 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 5 days post-dose | 21.6 mm | Standard Error 3.76 |
| Triamcinolone Acetonide 40 mg | Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) | 6 days post-dose | 20.5 mm | Standard Error 3.71 |
Secondary
Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab
Serum Amyloid A Protein (SAA) levels in blood serum were measured by a central laboratory in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Time frame: 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks.
Population: Modified Analysis Set (MAS) consisting of all FAS patients who were either re-treated or switched to canakinumab during the 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 Participants Re-treated With or Switched to Canakinumab | 4 weeks post-dose [N=47, 37] | 3.4 mg/L | Standard Deviation 3.67 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 24-hours post-dose [N=47, 36] | 129.0 mg/L | Standard Deviation 324.45 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 72-hours post-dose [N=54, 37] | 45.6 mg/L | Standard Deviation 163.45 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 7 days post-dose [N=56, 39] | 5.7 mg/L | Standard Deviation 8.9 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 8 weeks post-dose [N=38, 35] | 3.5 mg/L | Standard Deviation 4.24 |
| Canakinumab 150 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 12 weeks post-dose [N=38, 29] | 3.4 mg/L | Standard Deviation 2.37 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 8 weeks post-dose [N=38, 35] | 5.3 mg/L | Standard Deviation 13.41 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 4 weeks post-dose [N=47, 37] | 5.0 mg/L | Standard Deviation 7.02 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 7 days post-dose [N=56, 39] | 5.9 mg/L | Standard Deviation 8.34 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 24-hours post-dose [N=47, 36] | 145.9 mg/L | Standard Deviation 257.44 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 12 weeks post-dose [N=38, 29] | 4.8 mg/L | Standard Deviation 5.94 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab | 72-hours post-dose [N=54, 37] | 45.4 mg/L | Standard Deviation 97 |
Secondary
SF 36 Physical Function Score at Week 12
SF-36 measures impact of disease on overall quality of life (QoL). 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 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. Analysis of covariance (ANCOVA) model was used with treatment group and baseline SF-36 physical function subscore as covariates.
Time frame: Week 12
Population: 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 observations at Week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | SF 36 Physical Function Score at Week 12 | 81.46 Units on a scale | Standard Error 2.786 |
| Triamcinolone Acetonide 40 mg | SF 36 Physical Function Score at Week 12 | 78.75 Units on a scale | Standard Error 2.82 |
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 (VAS)
Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at Baseline and the confidence intervals were determined along with 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: Baseline to 7 days post-dose (randomization)
Population: 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 (VAS) | 25.0 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 (VAS) | 48.0 hours |
Secondary
Time to Complete Resolution of Pain; Survival Analysis
Kaplan-Meier estimates of the time to complete resolution of self-assessed pain intensity in the joint most affected and the confidence interval was determined. Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Pain was scored at Baseline; 6 and 12 hours; 1, 2, 3, 4, 5, 6, and 7 days post-dose.
Time frame: Baseline to 7 days post-dose (randomization)
Population: Full Analysis Set (FAS): All patients that received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab 150 mg | Time to Complete Resolution of Pain; Survival Analysis | 144.0 hours |
| Triamcinolone Acetonide 40 mg | Time to Complete Resolution of Pain; Survival Analysis | NA hours |
Secondary
Time to First Intake of Rescue Medication
Participants 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, participants were allowed to take a maximum of 30 mg of oral prednisolone 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. Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication. Kaplan-Meier estimates of the time to first intake of rescue medication, in hours, and the confidence interval were determined for the flare experienced at study entry (Baseline flare) and the last new flare (last post-baseline flare) that occurred up until the end of the first extension period (24 weeks).
Time frame: For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks).
Population: For the Baseline flare the population analyzed consisted of the Full Analysis Set (FAS). For the last post-baseline flare the population analyzed consisted of patients re-treated for at least one new flare. Patients who did not take rescue medication had the time-to-first rescue medication intake censored at 7 days post dosing and re-dosing.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab 150 mg | Time to First Intake of Rescue Medication | Baseline flare [N= 112, 114] | NA hours |
| Canakinumab 150 mg | Time to First Intake of Rescue Medication | Last post-baseline flare [N=25, 46] | 32 hours |
| Triamcinolone Acetonide 40 mg | Time to First Intake of Rescue Medication | Baseline flare [N= 112, 114] | 37.5 hours |
| Triamcinolone Acetonide 40 mg | Time to First Intake of Rescue Medication | Last post-baseline flare [N=25, 46] | NA hours |
Secondary
Time to First New Flare: Survival Analysis by Treatment Over 72 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.
Time frame: From randomization to the end of the second extension period (72 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: Survival Analysis by Treatment Over 72 Weeks | 254.0 days |
| Triamcinolone Acetonide 40 mg | Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks | 146.0 days |
Secondary
Time to the First New Gout Flare During 24 Weeks
Kaplan-Meier (KM) estimates of the time to first new flare and confidence intervals were determined. Participants met the definition of a 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. Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.
Time frame: From randomization to the end of the first extension period (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 the First New Gout Flare During 24 Weeks | NA days |
| Triamcinolone Acetonide 40 mg | Time to the First New Gout Flare During 24 Weeks | 146 days |