Canakinumab in the Treatment of Acute Gout Flares and Prevention of New Flares in Patients Unable to Use Non-steroidal Anti-inflammatory Drugs (NSAIDs) and/or Colchicine Including a 12 Weeks Extension and an Open-label 48 Weeks Extension Study

Acute Gout Clinical Trial

— ß-RELIEVED  

Official title:

A 12 Weeks Randomized, Controlled Core Study of ACZ885 (Canakinumab) on the Treatment and Prevention of Gout Flares in Patients With Frequent Flares for Whom NSAIDs and/or Colchicine Are Contraindicated, Not Tolerated or Ineffective, Including a 12-week Double-blind Extension Study and an Open-label 48 Week Extension Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01029652
• Other study ID #: CACZ885H2356
• Secondary ID: 2009-015018-23CA
• Status: Completed
• Phase: Phase 3
• First received: December 9, 2009
• Last updated: December 24, 2013
• Start date: December 2009
• Est. completion date: October 2010

Study information

• Verified date: September 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationLithuania: State Medicine Control Agency - Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosEstonia: The State Agency of MedicineGermany: Paul-Ehrlich-InstitutGuatemala: Ministry of Public Health and Social AssistanceMexico: Ministry of HealthNorway: Norwegian Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Pharmacological Committee, Ministry of HealthSingapore: Health Sciences AuthoritySweden: Medical Products AgencySwitzerland: SwissmedicUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of the 12-week core study was to demonstrate that canakinumab given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares in patients with frequent flares of gout for whom non-steroidal anti-inflammatory drugs (NSAIDs) and/ or colchicine are contraindicated, not tolerated, or ineffective. The efficacy of canakinumab was compared to the corticosteroid triamcinolone acetonide.

The purpose of the first 12-week extension study was to collect additional safety, tolerability and efficacy data in patients who have completed the core study CACZ885H2356.

The purpose of the second 48 week open-label extension study was to collect additional long-term safety and tolerability data in patients who have completed the first extension study CACZ885H2356E1.

Description:

Masking:

Core: Double Blind (Subject, Investigator) Extension 1: Double Blind (Subject, Investigator) Extension 2: Open-label, terminated

Other known NCT identifiers

• NCT01071213
• NCT01160016

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Core Study:

Inclusion criteria:

• Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout

• Onset of current acute gout flare within 5 days prior to study entry

• Baseline pain intensity = 50 mm on the 0-100 mm visual analog scale (VAS)

• History of = 3 gout flares within the 12 months prior to study entry

• Contraindication, intolerance, or lack of efficacy for non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine

Exclusion criteria:

• Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis

• Presence of severe renal function impairment

• Use of specified pain relief medications or biologics ( corticosteroids, narcotics, paracetamol/acetominophen, ibuprofen, colchicine, IL-blocker, and tumor necrosis factor inhibitor) within specified periods prior to study entry

• Live vaccinations within 3 months prior to randomization

• Requirement for administration of antibiotics against latent tuberculosis (TB)

• Refractory heart failure (Stage D)

• Unstable cardiac arrhythmias or unstable symptomatic coronary ischemia

• Any active or recurrent bacterial, fungal, or viral infection

Extension Study 1:

Inclusion Completion of the Core study. A patient was defined as completing the core study if they completed the study up to and including visit 7.

Exclusion

• Continuation in this extension study was considered inappropriate by the treating physician.

Extension Study 2:

Inclusion Completed of the first extension study CACZ885H2356E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).

Exclusion

-Continuation in this extension study was considered inappropriate by the treating physician

Other protocol-defined inclusion-exclusion criteria applied to the core and extension studies.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Gout
• Gout

Intervention

Drug:
• Canakinumab 150 mg
Canakinumab 150 mg was supplied in 6 mL glass vials each containing nominally 150 mg canakinumab (plus 20% overfill).
• Triamcinolone acetonide 40 mg
Triamcinolone acetonide 40 mg was supplied as a suspension.
• Placebo to canakinumab
Placebo to canakinumab was supplied in 6 mL glass vials containing placebo powder as a lyophilized cake.
• Placebo to triamcinolone acetonide
Placebo triamcinolone acetonide was supplied as a lipid emulsion similar in appearance to triamcinolone acetonide.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Darlinghurst	New South Wales
Australia	Novartis Investigative Site	Daw Park SA
Australia	Novartis Investigative Site	Fitzroy	Victoria
Australia	Novartis Investigative Site	Heidelberg	Victoria
Belgium	Novartis Investigative site	Gozee
Canada	Novartis Investigative site	Hamilton	Ontario
Canada	Novartis Investigative Site	Mount Pearl	Newfoundland and Labrador
Canada	Novartis Investigative site	St-John's	Newfoundland and Labrador
Colombia	Novartis Investigative site	Barranquilla
Colombia	Novartis Investigative site	Bogota
Colombia	Novartis Investigative site	Bucaramanga
Estonia	Novartis Investigative site	Parnu
Estonia	Novartis Investigative site	Tallinn
Estonia	Novartis Investigative site	Tartu
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Loehne
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative site	Munich
Guatemala	Novartis Investigative Site	Guatemala City
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Valmiera
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Kedainiai
Lithuania	Novartis Investigative site	Klaipeda
Lithuania	Novartis Investigative Site	Siauliai
Lithuania	Novartis Investigative Site	Vilnius
Mexico	Novartis Investigative site	Culiacan
Mexico	Novartis Investigative site	Guadalajara
Mexico	Novartis Investigative site	Mexicali
Norway	Novartis Investigative site	Oslo
Poland	Novartis Investigative site	Katowice
Poland	Novartis Investigative site	Kutno
Poland	Novartis Investigative site	Lublin
Poland	Novartis Investigative Site	Wroclaw
Russian Federation	Novartis Investigative site	Moscow
Russian Federation	Novartis Investigative site	Yaroslavl
Russian Federation	Novartis Investigative site	Yekaterinburg
Singapore	Novartis Investigative site	Singapore
Sweden	Novartis Investigative Site	Goeteborg
Sweden	Novartis Investigative site	Stockholm
Switzerland	Novartis Investigative Site	Lausanne
Ukraine	Novartis Investigative Site	Donetsk
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Zaporizhzhya

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Colombia,  Estonia,  Germany,  Guatemala,  Latvia,  Lithuania,  Mexico,  Norway,  Poland,  Russian Federation,  Singapore,  Sweden,  Switzerland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First New Flare	Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1).; Patients met definition of new flare if they had: Flare in joint, not a previously affected joint (at baseline or during study); Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.; Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before flare has resolved completely.	12 weeks	No
Primary	Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS)	Patients scored their pain intensity in the joint most affected at baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), at 72 hours post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.	72 hours post-dose (randomization)	No
Primary	Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (24 Weeks Overall)	This was the primary endpoint of both extension studies. Adverse event is defined as any unfavorable and unintended diagnosis, symptom, sign(including an abnormal laboratory finding),syndrome or disease which either occurs during the study, having been absent at baseline, or,if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.	24 weeks overall	Yes
Primary	Number of Participants With Adverse Events (AE), Death and Serious Adverse Events (72 Weeks Overall)	This was the primary endpoint of both extension studies. Adverse event is defined as any unfavorable and unintended diagnosis, symptom, sign(including an abnormal laboratory finding),syndrome or disease which either occurs during the study, having been absent at baseline, or,if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.	72 weeks overall	Yes
Secondary	Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100mm VAS)	The Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at baseline was determined along with the 95% confidence interval. Patients scored their pain intensity on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose.	From baseline to 7 days post dose (randomization)	No
Secondary	Time to Complete Resolution of Pain	Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose. The Kaplan-Meier estimates of time to complete resolution of self-assessed pain intensity in the joint most affected and their confidence intervals were determined.	7 days post-dose (randomization)	No
Secondary	Percentage of Participants With Complete Resolution of Pain	Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose. Complete Resolution of Pain is defined as no pain (None) on the Likert Scale. The Kaplan-Meier estimates of cumulative event rate = percentage of participants with event up to the end of the time interval.	7 days post-dose (randomization)	No
Secondary	Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks	Patients met definition of new flare if they had: Flare in joint, not a previously affected joint (at baseline or during study); Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.; Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.	12 weeks	No
Secondary	Mean Number of New Gout Flares Per Patient	Patients met definition of new flare if they had: Flare in joint, not a previously affected joint (at baseline or during study); Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.; Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.	12 weeks	No
Secondary	SF36 Physical Function Score at Week 12	The SF-36 measures the impact of disease on overall quality of life (QoL). This 36-item survey has 8 subscales that can be aggregated into physical- and mental-component summary scores. Scores are standardized with the use of norm-based methods based on an assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL. A negative change score indicates improvement. An ANCOVA model was used with treatment group and baseline SF-36 physical function subscore as covariates.	Week 12	No
Secondary	Time to First New Flare	Kaplan-Meier (KM) estimates of time to first new flare and confidence intervals were determined. Patients met definition of new flare if they had: Flare in joint, not a previously affected joint (at baseline or during study); Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.; Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.	24 weeks	No
Secondary	Mean Number of New Gout Flares Per Patient During the 24 Weeks of the Study	Patients met definition of new flare if they had: Flare in joint, not a previously affected joint (at baseline or during study); Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.; Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.	24 weeks	No
Secondary	Time to First Intake of Rescue Medication After the Last Post Baseline Flare.	The Kaplan-Meier estimates of medians and 95% confidence intervals were used to calculate the endpoint.	72 hours post-dose for the last post-baseline flare (during 24 weeks overall)	No
Secondary	Patient's Assessment of Gout Pain Intensity in the Most Affected Joint on a Visual Analog Scale (VAS) in Extension	Patients scored their pain intensity in the joint most affected at baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.	72 hours post-dose for the last post-baseline flare (during 24 weeks overall)	No
Secondary	Percentage of Participants With Maximum Severity of Last Post-baseline Flare (5-point Likert Scale)	Maximum severity is the maximum Likert score recorded after the start of the flare. Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme).	Last post-baseline flare (during 24 weeks overall)	No
Secondary	Amount of Rescue Medication Taken	Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows: Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed.; If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolon as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare.	7 days last post-baseline flare (during 24 weeks)	No
Secondary	Percentage of Participants Who Took Rescue Medication	Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments. Permitted rescue medications included acetaminophen 500 mg and/ or codeine 30 mg as needed. If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolone as needed per day for 2 days followed by up to 20 mg of prednisolone as needed per day for 3 subsequent days within 7 days after randomization or after re-dose/injection administration.	during 12 weeks core, 24 weeks overall	No
Secondary	High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels for Core and 24 Weeks Overall	High sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The analysis included treatment group, log-transformed protein level at baseline, and body mass index (BMI) at baseline as covariates.	72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)	No
Secondary	Physician's Global Assessment of Response to Treatment	The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity [Visual Analog Scale and Likert scale] and patient's global assessment of response to treatment).	72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)	No
Secondary	Patient's Global Assessment of Response to Treatment	Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured.	72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)	No
Secondary	Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint	The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that "there is pain", patient states "there is pain and winces", and patient states "there is pain, winces, and withdraws" on palpation or passive movement of the affected study joint; Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; and Erythema: Present or absent. The percentage of patients in each category is reported.	72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (during 24 weeks overall)	No
Secondary	Physician's Assessment of Range of Motion of the Most Affected Joint	The study physician assessed the range of motion of the most affected joint for range of motion on a 5-point Likert scale: Normal, mildly restricted, moderately restricted, severely restricted, immobilized. The percentage of patients in each category is reported.	72 hours post-dose (randomization), 72 hours post-dose for the last post-baseline flare (24 weeks overall)	No
Secondary	Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale)	Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme).	7 days post dose (randomization), 24 weeks post-dose	No
Secondary	Time to First New Flare: Survival Analysis by Treatment (72 Weeks Overall)	Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1).; Patients met definition of new flare if they had: Flare in joint, not a previously affected joint (at baseline or during study); Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.; Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before flare has resolved completely.	72 weeks overall	No
Secondary	Flare Rate Per Year	Flare rate was calculated as the number of new flares over the period of observation in years. Flare rate was calculated using only those new flares before switching to canakinumab.; Patients met definition of new flare if they had: Flare in joint, not a previously affected joint (at baseline or during study); Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.; Patients did not meet criterion of having new gout flare if: · Increasing/renewed gout pain in an affected joint before the flare has resolved completely.	72 weeks overall	No
Secondary	High-sensitivity C-reactive Protein (hsCRP) Levels for Patients Re-treated With or Switched to Canakinumab	High sensitivity C-reactive protein (hsCRP) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)	No
Secondary	Serum Amyloid A Protein (SAA) Levels for Patients Re-treated With or Switched to Canakinumab	Serum Amyloid A Protein (SAA) levels were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analytes were measured by a central laboratory. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	24 hours, 72 hours, 7 days, 4 weeks, 8 weeks and 12 weeks post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)	No
Secondary	Physician's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab	The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's assessments (pain intensity [Visual Analog Scale and Likert scale] and patient's global assessment of response to treatment). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	72 hours post-dose , 7 days post-dose for the last post-baseline flare for patients re-treated with canakinumab or first post-baseline flare treated with canakinumab for patients switched treatment (during 72 weeks overall)	No
Secondary	Patient's Assessment of Gout Pain Intensity in the Currently Most-affected Joint (Likert Scale)	Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme). It participant had a new flare, they also scored the maximum amount of acute gout pain in the most affected joint since the onset of a new flare on 5 point Likert scale (none, mild, moderate, severe, extreme). The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)	No
Secondary	Patient's Global Assessment of Response to Treatment for Patients Re-treated or Switched to Canakinumab	Patients made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. Percentage of participants in each category for both core and extension periods were measured. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)	No
Secondary	Physician's Assessment of Joint Tenderness for Patients Re-treated or Switched to Canakinumab	The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that "there is pain", patient states "there is pain and winces", and patient states "there is pain, winces, and withdraws" on palpation or passive movement of the affected study joint; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)	No
Secondary	Physician's Assessment of Joint Swelling for Patients Re-treated or Switched to Canakinumab	The study physician assessed the most affected joint for: Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	72 hours post-dose , 7 days post dose last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)	No
Secondary	Physician's Assessment of Erythema for Patients Re-treated or Switched to Canakinumab	The study physician assessed the most affected joint for Erythema: Present or absent. The percentage of patients in each category is reported. The treatment effect reported for canakinumab arm was for last post-baseline flare after re-treated with canakinumab and for patient which switched to Canakinumab arm was for first post-baseline flare after receiving the first dose of canakinumab.	72 hours post-dose , 7 days post dose for the last post-baseline flare for patients re-treated with canakinumab or the first post-baseline flare treated with canakinumab for patients who switched treatment (during 72 weeks overall)	No