Trial Outcomes & Findings for Efficacy, Safety and Tolerability of ACZ885 in Patients With Active Rheumatoid Arthritis (NCT NCT00424346)

Last Updated: 2014-02-10

Results Overview

Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Details on each of these components are provided in Outcome Measures 10-16. Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

274 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2014-02-10

Participant Flow

277 patients were randomized in core (CACZ885A2201): 71 were assigned to ACZ885 600 mg intravenous(iv) + 300 mg subcutaneous each 2 weeks(sc q2wk), 66 to ACZ885 300 mg sc q2wk, 69 to ACZ885 150 mg sc q4wk, 71 to placebo. 3 were randomized but not treated. All other 274 (98.9%) were treated and had post-baseline efficacy data.

Enrollment in core \& CACZ885A2201E2 was determined by how many entered first extension study. Study protocols did not mandate that patients continue treatment in the extension phase and furthermore the reason for not continuing from the Core to the Extension phase was not capture. A total of 6.6% completed extensions.

Participant milestones

Participant milestones
Measure	Canakinumab 600 mg IV + 300 mg q2wk Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks. Participants in this treatment group who participated in the Extension Phase are represented in the 'Canakinumab 300 mg q2wk' treatment group in the Extension Phase table below.	Canakinumab 300 mg q2wk Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Core Study STARTED	71	64	69	70
Core Study COMPLETED	62	56	65	63
Core Study NOT COMPLETED	9	8	4	7
Extension Phase STARTED	0	110	59	58
Extension Phase COMPLETED	0	8	4	3
Extension Phase NOT COMPLETED	0	102	55	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Canakinumab 600 mg IV + 300 mg q2wk Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks. Participants in this treatment group who participated in the Extension Phase are represented in the 'Canakinumab 300 mg q2wk' treatment group in the Extension Phase table below.	Canakinumab 300 mg q2wk Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Core Study Adverse Event	5	3	1	1
Core Study Abnormal Laboratory Values	0	1	0	0
Core Study Lack of Efficacy	1	3	0	4
Core Study Withdrawal by Subject	1	0	0	2
Core Study Lost to Follow-up	1	1	0	0
Core Study Administrative Problems	1	0	1	0
Core Study Protocol Violation	0	0	2	0
Extension Phase Adverse Event	0	9	5	4
Extension Phase Lack of Efficacy	0	16	14	11
Extension Phase Withdrawal by Subject	0	5	3	4
Extension Phase Lost to Follow-up	0	2	0	0
Extension Phase Administrative Problems	0	69	32	35
Extension Phase Death	0	0	0	1
Extension Phase Protocol Violation	0	1	1	0

Baseline Characteristics

Efficacy, Safety and Tolerability of ACZ885 in Patients With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Total n=274 Participants Total of all reporting groups
Age, Customized ≥18 - <41 years	NA participants n=5 Participants	7 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	19 participants n=21 Participants
Age, Customized ≥41 - <65 years	NA participants n=5 Participants	66 participants n=7 Participants	39 participants n=5 Participants	38 participants n=4 Participants	143 participants n=21 Participants
Age, Customized ≥65 - <75 years	NA participants n=5 Participants	25 participants n=7 Participants	12 participants n=5 Participants	12 participants n=4 Participants	49 participants n=21 Participants
Age, Customized ≥75 years	NA participants n=5 Participants	12 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	16 participants n=21 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	57 Participants n=7 Participants	56 Participants n=5 Participants	52 Participants n=4 Participants	225 Participants n=21 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants	18 Participants n=4 Participants	49 Participants n=21 Participants
Gender Female	0 participants n=5 Participants	94 participants n=7 Participants	47 participants n=5 Participants	44 participants n=4 Participants	185 participants n=21 Participants
Gender Male	0 participants n=5 Participants	16 participants n=7 Participants	12 participants n=5 Participants	14 participants n=4 Participants	42 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The intent-to-treat (ITT) population consisted of all patients as randomized that received at least one dose of study drug and had at least one post-baseline efficacy assessment. The number of patients in the analysis includes those with ACR50 evaluation. Last observation carried forward was applied for all the component variables.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=68 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12	9.9 percentage of participants Interval 0.31 to 2.65	23.4 percentage of participants Interval 0.91 to 6.05	26.5 percentage of participants Interval 1.12 to 7.05	11.4 percentage of participants

PRIMARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124

Population: The Extension Study intent-to-treat (ITT) population consisted of all patients who entered the extension study and who received at least one dose of study drug in the extension studies. The number of patients in the analysis at each time point (N) includes those with ACR20 evaluation data available.

Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR20 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=110 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=59 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=58 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 24 [N=105, 57, 56]	52.4 percentage of participants	64.9 percentage of participants	66.1 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 36 [N=100, 48, 49]	57.0 percentage of participants	66.7 percentage of participants	63.3 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 48 [N=95, 43, 47]	66.3 percentage of participants	81.4 percentage of participants	72.3 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 60 [N=87, 40, 42]	60.9 percentage of participants	75.0 percentage of participants	73.8 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 72 [N=66, 34, 27]	62.1 percentage of participants	76.5 percentage of participants	74.1 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 88 [N=43, 25, 23]	67.4 percentage of participants	72.0 percentage of participants	82.6 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 100 [N=21, 12, 14]	81.0 percentage of participants	75.0 percentage of participants	91.7 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 112 [N=13, 8, 6]	76.9 percentage of participants	75.0 percentage of participants	66.7 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase Week 124 [N=2, 1, 1]	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase End of Study Visit [N=103, 53, 54]	51.5 percentage of participants	54.7 percentage of participants	61.1 percentage of participants	—

PRIMARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124

Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=110 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=59 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=58 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 24 [N=106, 57, 56]	18.9 percentage of participants	29.8 percentage of participants	37.5 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 36 [N=100, 48, 49]	24.0 percentage of participants	31.3 percentage of participants	32.7 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 48 [N=95, 43, 47]	34.7 percentage of participants	48.8 percentage of participants	34.0 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 60 [N=87, 40, 42]	34.5 percentage of participants	42.5 percentage of participants	42.9 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 72 [N=66, 34, 27]	37.9 percentage of participants	58.8 percentage of participants	48.1 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 88 [N=43, 25, 23]	39.5 percentage of participants	44.0 percentage of participants	52.2 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 100 [N=21, 13, 14]	47.6 percentage of participants	30.8 percentage of participants	57.1 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 112 [N=13, 8, 6]	23.1 percentage of participants	62.5 percentage of participants	66.7 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase Week 124 [N=2, 1, 1]	50.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase End of Study Visit [N=103, 53, 54]	23.3 percentage of participants	35.8 percentage of participants	35.2 percentage of participants	—

PRIMARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124

Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR70 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=110 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=59 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=58 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 24 [N=106, 57, 56]	5.7 percentage of participants	10.5 percentage of participants	14.3 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 36 [N=100, 48, 49]	7.0 percentage of participants	4.2 percentage of participants	12.2 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 48 [N=96, 43, 47]	10.4 percentage of participants	9.3 percentage of participants	6.4 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 60 [N=87, 40, 42]	16.1 percentage of participants	17.5 percentage of participants	19.0 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 72 [N=66, 34, 27]	15.2 percentage of participants	20.6 percentage of participants	14.8 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 88 [N=44, 25, 23]	15.9 percentage of participants	16.0 percentage of participants	17.4 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 100 [N=21, 14, 14]	14.3 percentage of participants	21.4 percentage of participants	28.6 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 112 [N=13, 8, 6]	7.7 percentage of participants	37.5 percentage of participants	33.3 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase Week 124 [N=2, 1, 1]	50.0 percentage of participants	100.0 percentage of participants	0.0 percentage of participants	—
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase End of Study Visit [N=103, 54, 54]	13.6 percentage of participants	16.7 percentage of participants	13.0 percentage of participants	—

PRIMARY outcome

Timeframe: Baseline and Weeks 24, 72 and 112

Population: The Extension Study intent-to-treat (ITT) population consisted of all patients who entered the extension study and who received at least one dose of study drug in the extension studies. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) in mg/L; * Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=110 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=59 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=58 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase Week 24 [N=103, 56, 54]	-1.60 scores on a scale Standard Deviation 1.171	-1.82 scores on a scale Standard Deviation 1.333	-1.93 scores on a scale Standard Deviation 1.474	—
Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase Week 72 [N=63, 31, 26]	-2.18 scores on a scale Standard Deviation 1.302	-2.58 scores on a scale Standard Deviation 1.232	-2.21 scores on a scale Standard Deviation 1.132	—
Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase Week 112 [N=13, 8, 6]	-2.00 scores on a scale Standard Deviation 1.110	-2.73 scores on a scale Standard Deviation 1.252	-2.59 scores on a scale Standard Deviation 1.916	—
Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase End of Study Visit [N=100, 52, 49}	-1.83 scores on a scale Standard Deviation 1.434	-1.79 scores on a scale Standard Deviation 1.551	-1.86 scores on a scale Standard Deviation 1.621	—

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR50 evaluation. Last observation carried forward was applied for all the component variables. "N" indicates the number of patients included at each time point.

Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 Responders at Week 2 [N=70, 64, 69, 70]	2.9 percentage of participants	1.6 percentage of participants	5.8 percentage of participants	4.3 percentage of participants
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 Responders at Week 4 [N=71, 64, 69, 70]	1.4 percentage of participants	7.8 percentage of participants	7.2 percentage of participants	4.3 percentage of participants
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8 Responders at Week 8 [N=71, 64, 69, 70]	4.2 percentage of participants	17.2 percentage of participants	17.4 percentage of participants	7.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR20 evaluation. Last observation carried forward was applied for all the component variables. "N" indicates the number of patients included at each time point.

Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered ACR20 non-responders if they failed the ACR20 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders Responders at Week 2 [N=70, 64, 69, 70]	17.1 percentage of participants Interval 1.06 to 4.74	29.7 percentage of participants Interval 1.27 to 5.82	23.2 percentage of participants Interval 1.37 to 6.18	14.3 percentage of participants
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders Responders at Week 4 [N=71, 64, 68, 70]	29.6 percentage of participants	37.5 percentage of participants	39.7 percentage of participants	20.0 percentage of participants
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders Responders at Week 8 [N=71, 64, 68, 70]	35.2 percentage of participants	43.8 percentage of participants	42.6 percentage of participants	27.1 percentage of participants
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders Responders at Week 12 [N=71, 64, 68, 70]	43.7 percentage of participants	48.4 percentage of participants	50.0 percentage of participants	28.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR70 evaluation. Last observation carried forward was applied for all the component variables. "N" indicates the number of patients included at each time point.

Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]). Participants were considered ACR70 non-responders if they failed the ACR70 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders Responders at Week 2 [N=70, 64, 69, 70]	0.0 percentage of participants Interval 0.27 to 10.71	1.6 percentage of participants Interval 0.14 to 7.61	0.0 percentage of participants Interval 0.37 to 12.12	0.0 percentage of participants
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders Responders at Week 4 [N=71, 64, 69, 70]	0.0 percentage of participants	1.6 percentage of participants	4.3 percentage of participants	0.0 percentage of participants
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders Responders at Week 8 [N=71, 64, 69, 70]	0.0 percentage of participants	4.7 percentage of participants	5.8 percentage of participants	2.9 percentage of participants
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders Responders at Week 12 [N=71, 64, 69, 70]	4.2 percentage of participants	3.1 percentage of participants	5.8 percentage of participants	2.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The intent-to-treat (ITT) population. The number of patients in the analysis includes those with ACR evaluation. Last observation carried forward was applied for all the component variables.

To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, participants were categorized as follows: 1. Did not attain an ACR20 response; 2. Attained a 20% but not a 50% response; 3. Attained a 50% but not a 70% response; 4. Attained a 70% or greater response. A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire \[HAQ\] score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=68 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 No response	40 participants	33 participants	34 participants	50 participants
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 ACR20 - not ACR50 response	24 participants	16 participants	16 participants	12 participants
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 ACR50 - not ACR70 response	4 participants	13 participants	14 participants	6 participants
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12 ACR70 response	3 participants	2 participants	4 participants	2 participants

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: ITT Population, the number of patients included in the analysis at each time point is indicated by "N". Last observation carried forward was utilized.

The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Swollen 28-joint Count Week 2 [N=70, 64, 69, 70]	-2.4 swollen joints Standard Error 0.53	-2.7 swollen joints Standard Error 0.56	-3.1 swollen joints Standard Error 0.54	-2.3 swollen joints Standard Error 0.54
Change From Baseline in Swollen 28-joint Count Week 4 [N=71, 64, 69, 70]	-3.4 swollen joints Standard Error 0.55	-4.0 swollen joints Standard Error 0.58	-4.6 swollen joints Standard Error 0.56	-3.0 swollen joints Standard Error 0.56
Change From Baseline in Swollen 28-joint Count Week 8 [N=71, 64, 69, 70]	-4.0 swollen joints Standard Error 0.58	-4.4 swollen joints Standard Error 0.61	-4.9 swollen joints Standard Error 0.59	-3.3 swollen joints Standard Error 0.59
Change From Baseline in Swollen 28-joint Count Week 12 [N=71, 64, 69, 70]	-4.6 swollen joints Standard Error 0.64	-5.3 swollen joints Standard Error 0.67	-5.2 swollen joints Standard Error 0.65	-3.4 swollen joints Standard Error 0.65

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: ITT Population, the number of patients included in the analysis at each time point is indicated by "N". Last observation carried forward was utilized.

The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Tender 28-joint Count Week 2 [N=70, 64, 69, 70]	-3.0 tender joints Standard Error 0.68	-2.1 tender joints Standard Error 0.71	-3.6 tender joints Standard Error 0.68	-3.2 tender joints Standard Error 0.69
Change From Baseline in Tender 28-joint Count Week 4 [N=71, 64, 69, 70]	-4.1 tender joints Standard Error 0.77	-4.0 tender joints Standard Error 0.80	-5.0 tender joints Standard Error 0.78	-4.2 tender joints Standard Error 0.78
Change From Baseline in Tender 28-joint Count Week 8 [N=71, 64, 69, 70]	-4.6 tender joints Standard Error 0.79	-4.7 tender joints Standard Error 0.83	-5.4 tender joints Standard Error 0.80	-4.7 tender joints Standard Error 0.80
Change From Baseline in Tender 28-joint Count Week 12 [N=71, 64, 69, 70]	-4.3 tender joints Standard Error 0.86	-4.8 tender joints Standard Error 0.90	-6.3 tender joints Standard Error 0.87	-4.5 tender joints Standard Error 0.87

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by

The patient's assessment of pain was performed using a 100 mm visual analog scale (VAS) ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=68 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Patient's Pain Intensity Week 2 [N=70, 64, 68, 70]	-6.7 scores on a scale Standard Error 2.20	-8.0 scores on a scale Standard Error 2.29	-8.3 scores on a scale Standard Error 2.23	-4.2 scores on a scale Standard Error 2.22
Change From Baseline in Patient's Pain Intensity Week 4 [N=71, 64, 68, 70]	-9.1 scores on a scale Standard Error 2.40	-9.6 scores on a scale Standard Error 2.52	-11.4 scores on a scale Standard Error 2.45	-5.6 scores on a scale Standard Error 2.45
Change From Baseline in Patient's Pain Intensity Week 8 [N=71, 64, 68, 70]	-12.2 scores on a scale Standard Error 2.66	-12.5 scores on a scale Standard Error 2.80	-14.0 scores on a scale Standard Error 2.72	-7.6 scores on a scale Standard Error 2.72
Change From Baseline in Patient's Pain Intensity Week 12 [N=71, 64, 68, 70]	-14.2 scores on a scale Standard Error 2.72	-15.1 scores on a scale Standard Error 2.87	-17.0 scores on a scale Standard Error 2.78	-10.5 scores on a scale Standard Error 2.78

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by

The patient's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100), after the question "Considering all the ways your arthritis affects you, draw a line on the scale for how well you are doing". The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=68 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Patient's Global Assessment of Disease Activity Week 2 [N=70, 64, 68, 70]	-6.4 scores on a scale Standard Error 2.12	-7.5 scores on a scale Standard Error 2.21	-7.9 scores on a scale Standard Error 2.15	-5.0 scores on a scale Standard Error 2.15
Change From Baseline in Patient's Global Assessment of Disease Activity Week 4 [N= 71, 64, 68, 70]	-9.4 scores on a scale Standard Error 2.28	-11.2 scores on a scale Standard Error 2.39	-12.8 scores on a scale Standard Error 2.33	-6.1 scores on a scale Standard Error 2.33
Change From Baseline in Patient's Global Assessment of Disease Activity Week 8 [N= 71, 64, 68, 70]	-13.9 scores on a scale Standard Error 2.63	-15.7 scores on a scale Standard Error 2.76	-13.8 scores on a scale Standard Error 2.68	-6.9 scores on a scale Standard Error 2.68
Change From Baseline in Patient's Global Assessment of Disease Activity Week 12 [N= 71, 64, 68, 70]	-14.5 scores on a scale Standard Error 2.61	-17.5 scores on a scale Standard Error 2.74	-17.6 scores on a scale Standard Error 2.66	-10.1 scores on a scale Standard Error 2.66

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by

The physician's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment of disease activity when performing their own assessment on that patient. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=68 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Physician's Global Assessment of Disease Activity Week 2 [N=70, 64, 68, 69]	-13.3 scores on a scale Standard Error 2.21	-14.8 scores on a scale Standard Error 2.34	-15.2 scores on a scale Standard Error 2.25	-9.3 scores on a scale Standard Error 2.25
Change From Baseline in Physician's Global Assessment of Disease Activity Week 4 [N=71, 64, 68, 70]	-17.7 scores on a scale Standard Error 2.40	-20.1 scores on a scale Standard Error 2.55	-20.3 scores on a scale Standard Error 2.46	-12.2 scores on a scale Standard Error 2.45
Change From Baseline in Physician's Global Assessment of Disease Activity Week 8 [N=71, 64, 68, 70]	-20.8 scores on a scale Standard Error 2.68	-22.6 scores on a scale Standard Error 2.86	-23.6 scores on a scale Standard Error 2.75	-16.5 scores on a scale Standard Error 2.74
Change From Baseline in Physician's Global Assessment of Disease Activity Week 12 [N=71, 64, 68, 70]	-21.6 scores on a scale Standard Error 2.82	-24.0 scores on a scale Standard Error 3.01	-26.4 scores on a scale Standard Error 2.90	-17.6 scores on a scale Standard Error 2.88

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Population: ITT Population, only patients with a value at both Baseline and post-baseline are included in the analysis. The number of patients included at each time point is indicated by "N". Last observation carried forward was utilized.

The patient health assessment questionnaire (HAQ) was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from Baseline score indicates improvement in disability status. Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Health Assessment Questionnaire (HAQ) Score Week 2 [N=70, 64, 69, 70]	-0.1 scores on a scale Standard Error 0.04	0.0 scores on a scale Standard Error 0.05	-0.1 scores on a scale Standard Error 0.04	-0.1 scores on a scale Standard Error 0.04
Change From Baseline in Health Assessment Questionnaire (HAQ) Score Week 4 [N=71, 64, 69, 70]	-0.1 scores on a scale Standard Error 0.05	-0.1 scores on a scale Standard Error 0.05	-0.2 scores on a scale Standard Error 0.05	-0.1 scores on a scale Standard Error 0.05
Change From Baseline in Health Assessment Questionnaire (HAQ) Score Week 8 [N=71, 64, 69, 70]	-0.2 scores on a scale Standard Error 0.06	-0.1 scores on a scale Standard Error 0.06	-0.2 scores on a scale Standard Error 0.06	-0.1 scores on a scale Standard Error 0.06
Change From Baseline in Health Assessment Questionnaire (HAQ) Score Week 12 [N=71, 64, 69, 70]	-0.2 scores on a scale Standard Error 0.06	-0.2 scores on a scale Standard Error 0.06	-0.2 scores on a scale Standard Error 0.06	-0.1 scores on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels Week 2 [N=69, 64, 67, 70]	-5.6 mg/L Standard Error 1.72	-5.8 mg/L Standard Error 1.79	-4.7 mg/L Standard Error 1.75	-1.7 mg/L Standard Error 1.74
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels Week 4 [N=71, 64, 69, 70]	-5.2 mg/L Standard Error 1.69	-7.4 mg/L Standard Error 1.78	-6.5 mg/L Standard Error 1.72	-1.7 mg/L Standard Error 1.73
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels Week 8 [N=71, 64, 69, 70]	-4.3 mg/L Standard Error 1.72	-6.9 mg/L Standard Error 1.82	-3.5 mg/L Standard Error 1.75	0.0 mg/L Standard Error 1.77
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels Week 12 [N=71, 64, 69, 70]	-5.6 mg/L Standard Error 1.89	-3.4 mg/L Standard Error 1.99	-8.0 mg/L Standard Error 1.92	-0.7 mg/L Standard Error 1.94

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=68 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Disease Activity Score (DAS) 28 Week 2 [N=69, 64, 66, 70]	-0.7 scores on a scale Standard Error 0.11	-0.7 scores on a scale Standard Error 0.11	-0.8 scores on a scale Standard Error 0.11	-0.5 scores on a scale Standard Error 0.11
Change From Baseline in Disease Activity Score (DAS) 28 Week 4 [N=71, 64, 68, 70]	-0.9 scores on a scale Standard Error 0.13	-1.0 scores on a scale Standard Error 0.13	-1.1 scores on a scale Standard Error 0.13	-0.7 scores on a scale Standard Error 0.13
Change From Baseline in Disease Activity Score (DAS) 28 Week 8 [N=71, 64, 68, 70]	-1.1 scores on a scale Standard Error 0.14	-1.2 scores on a scale Standard Error 0.15	-1.2 scores on a scale Standard Error 0.14	-0.8 scores on a scale Standard Error 0.14
Change From Baseline in Disease Activity Score (DAS) 28 Week 12 [N=71, 64, 68, 70]	-1.2 scores on a scale Standard Error 0.15	-1.3 scores on a scale Standard Error 0.16	-1.5 scores on a scale Standard Error 0.15	-0.9 scores on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. A negative change from Baseline score indicates improvement.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Erythrocyte Sedimentation Rate Week 2 [N=68, 64, 67, 69]	-9.0 mm/hr Standard Deviation 12.85	-8.2 mm/hr Standard Deviation 15.97	-9.0 mm/hr Standard Deviation 12.43	-2.9 mm/hr Standard Deviation 11.62
Change From Baseline in Erythrocyte Sedimentation Rate Week 4 [N=71, 64, 69, 70]	-9.2 mm/hr Standard Deviation 15.11	-9.6 mm/hr Standard Deviation 17.43	-11.8 mm/hr Standard Deviation 14.71	-2.6 mm/hr Standard Deviation 12.94
Change From Baseline in Erythrocyte Sedimentation Rate Week 8 [N=71, 64, 69, 70]	-11.3 mm/hr Standard Deviation 16.28	-12.3 mm/hr Standard Deviation 16.02	-12.8 mm/hr Standard Deviation 13.89	-4.4 mm/hr Standard Deviation 15.65
Change From Baseline in Erythrocyte Sedimentation Rate Week 12 [N=71, 64, 69, 70]	-11.2 mm/hr Standard Deviation 18.20	-11.1 mm/hr Standard Deviation 18.12	-15.1 mm/hr Standard Deviation 14.96	-4.1 mm/hr Standard Deviation 16.73

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) that is an indicator of inflammation and rheumatoid arthritis.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Rheumatoid Factor Concentration Week 4 [N=70, 62, 68, 67]	-6.7 kIU/L Standard Deviation 71.53	-10.6 kIU/L Standard Deviation 99.36	-16.1 kIU/L Standard Deviation 144.18	-0.9 kIU/L Standard Deviation 85.28
Change From Baseline in Rheumatoid Factor Concentration Week 8 [N=70, 63, 69, 70]	-2.6 kIU/L Standard Deviation 117.30	22.7 kIU/L Standard Deviation 134.66	-57.1 kIU/L Standard Deviation 442.24	6.0 kIU/L Standard Deviation 91.51
Change From Baseline in Rheumatoid Factor Concentration Week 12 [N=70, 64, 69, 70]	2.0 kIU/L Standard Deviation 135.70	29.7 kIU/L Standard Deviation 144.91	-50.7 kIU/L Standard Deviation 531.68	16.9 kIU/L Standard Deviation 110.03

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical component: Week 2 [N=61, 61, 59, 64]	1.73 scores on a scale Standard Deviation 5.013	0.27 scores on a scale Standard Deviation 5.648	2.85 scores on a scale Standard Deviation 4.999	2.03 scores on a scale Standard Deviation 6.996
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical component: Week 4 [N=65, 62, 63, 67]	2.71 scores on a scale Standard Deviation 6.582	2.30 scores on a scale Standard Deviation 6.972	3.21 scores on a scale Standard Deviation 6.406	2.43 scores on a scale Standard Deviation 7.134
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical component: Week 8 [N=67, 62, 63, 68]	2.62 scores on a scale Standard Deviation 6.528	2.75 scores on a scale Standard Deviation 7.331	4.29 scores on a scale Standard Deviation 8.757	1.96 scores on a scale Standard Deviation 7.464
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical component: Week 12 [N=68, 62, 63, 68]	4.03 scores on a scale Standard Deviation 6.519	3.05 scores on a scale Standard Deviation 7.847	5.73 scores on a scale Standard Deviation 8.612	2.69 scores on a scale Standard Deviation 7.846
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental component: Week 2 [N=61, 61, 59, 64]	0.56 scores on a scale Standard Deviation 8.831	2.64 scores on a scale Standard Deviation 8.425	1.21 scores on a scale Standard Deviation 8.486	0.63 scores on a scale Standard Deviation 9.234
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental component: Week 4 [N=65, 62, 63, 67]	2.18 scores on a scale Standard Deviation 9.660	2.75 scores on a scale Standard Deviation 11.364	2.23 scores on a scale Standard Deviation 8.634	1.75 scores on a scale Standard Deviation 8.331
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental component: Week 8 [N=67, 62, 63, 68]	2.29 scores on a scale Standard Deviation 10.505	2.83 scores on a scale Standard Deviation 11.760	3.04 scores on a scale Standard Deviation 9.307	1.18 scores on a scale Standard Deviation 9.580
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental component: Week 12 [N=68, 62, 63, 68]	1.44 scores on a scale Standard Deviation 9.988	3.34 scores on a scale Standard Deviation 11.927	4.06 scores on a scale Standard Deviation 10.952	0.35 scores on a scale Standard Deviation 9.294

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 8 and 12

The fatigue subscale of the FACIT is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants respond to each item on a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT Fatigue subscale scores range from 0 to 52, where higher scores represent less fatigue. Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline FACIT-F value as a covariate.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=71 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=64 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=69 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo n=70 Participants Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) Week 2 [N=62, 63, 63, 64]	2.5 scores on a scale Standard Error 0.90	1.6 scores on a scale Standard Error 0.87	3.7 scores on a scale Standard Error 0.89	2.5 scores on a scale Standard Error 0.89
Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) Week 4 [N=66, 64, 66, 67]	3.8 scores on a scale Standard Error 0.99	3.3 scores on a scale Standard Error 0.99	4.9 scores on a scale Standard Error 0.98	2.1 scores on a scale Standard Error 1.00
Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) Week 8 [N=67, 64, 66, 67]	4.2 scores on a scale Standard Error 1.13	4.0 scores on a scale Standard Error 1.15	4.6 scores on a scale Standard Error 1.13	2.1 scores on a scale Standard Error 1.15
Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) Week 12 [N=67, 64, 66, 67]	4.9 scores on a scale Standard Error 1.14	3.8 scores on a scale Standard Error 1.15	5.7 scores on a scale Standard Error 1.14	1.4 scores on a scale Standard Error 1.16

SECONDARY outcome

Timeframe: Baseline and End of Study (up to 124 weeks)

Population: Extension Study ITT population.

To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, patients were categorized as follows: 1. Did not attain an ACR20 response; 2. Attained a 20% but not a 50% response; 3. Attained a 50% but not a 70% response; 4. Attained a 70% or greater response. A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire \[HAQ\] score); * Acute phase reactant (high sensitivity C-reactive Protein \[hsCRP\]).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=103 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=53 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=54 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study No response	50 participants	24 participants	21 participants	—
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study ACR20 - not ACR50 response	29 participants	10 participants	14 participants	—
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study ACR50 - not ACR70 response	10 participants	10 participants	12 participants	—
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study ACR70 response	14 participants	9 participants	7 participants	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=110 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=59 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=58 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 24 [N=105, 58, 55]	-6.04 swollen joints Standard Deviation 4.892	-5.70 swollen joints Standard Deviation 5.119	-6.93 swollen joints Standard Deviation 5.300	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 36 [N=100, 49, 49]	-7.12 swollen joints Standard Deviation 4.828	-6.79 swollen joints Standard Deviation 4.365	-7.05 swollen joints Standard Deviation 4.726	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 48 [N=95, 44, 47]	-7.72 swollen joints Standard Deviation 4.171	-7.52 swollen joints Standard Deviation 3.622	-7.74 swollen joints Standard Deviation 4.454	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 60 [N=89, 40, 43]	-7.69 swollen joints Standard Deviation 4.670	-7.38 swollen joints Standard Deviation 3.737	-8.65 swollen joints Standard Deviation 4.825	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 72 [N=66, 35, 27]	-7.41 swollen joints Standard Deviation 5.311	-7.94 swollen joints Standard Deviation 4.143	-7.60 swollen joints Standard Deviation 3.678	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 88 [N=44, 25, 22]	-8.38 swollen joints Standard Deviation 4.369	-7.24 swollen joints Standard Deviation 3.666	-7.50 swollen joints Standard Deviation 3.389	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 100 [N=21, 13, 14]	-8.29 swollen joints Standard Deviation 4.285	-8.15 swollen joints Standard Deviation 2.824	-7.56 swollen joints Standard Deviation 2.974	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 112 [N=13, 8, 6]	-7.39 swollen joints Standard Deviation 5.308	-9.50 swollen joints Standard Deviation 2.976	-5.83 swollen joints Standard Deviation 5.636	—
Change From Baseline in Swollen 28-joint Count During the Extension Study Week 124 [N=2, 1, 1]	-6.50 swollen joints Standard Deviation 0.707	-16.00 swollen joints Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	-4.00 swollen joints Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	—
Change From Baseline in Swollen 28-joint Count During the Extension Study End of Study Visit [N=103, 55, 53]	-6.36 swollen joints Standard Deviation 5.477	-5.99 swollen joints Standard Deviation 4.937	-6.67 swollen joints Standard Deviation 6.350	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=105 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=58 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=55 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Tender 28-joint Count During the Extension Study Week 24 [N=105, 58, 55]	-6.93 tender joints Standard Deviation 7.078	-8.27 tender joints Standard Deviation 7.555	-8.49 tender joints Standard Deviation 7.298	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 36 [N=100, 49, 49]	-7.92 tender joints Standard Deviation 6.793	-9.83 tender joints Standard Deviation 6.459	-8.95 tender joints Standard Deviation 7.154	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 48 [N=95, 44, 47]	-8.64 tender joints Standard Deviation 7.193	-10.75 tender joints Standard Deviation 5.948	-10.05 tender joints Standard Deviation 6.321	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 60 [N=89, 40, 43]	-8.52 tender joints Standard Deviation 6.915	-11.10 tender joints Standard Deviation 6.484	-10.76 tender joints Standard Deviation 6.185	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 72 [N=66, 35, 27]	-8.71 tender joints Standard Deviation 7.556	-11.37 tender joints Standard Deviation 7.436	-9.56 tender joints Standard Deviation 4.722	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 88 [N=44, 25, 22]	-10.34 tender joints Standard Deviation 5.995	-10.76 tender joints Standard Deviation 7.184	-9.98 tender joints Standard Deviation 4.964	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 100 [N=21, 13, 14]	-8.53 tender joints Standard Deviation 5.780	-12.00 tender joints Standard Deviation 5.307	-9.08 tender joints Standard Deviation 4.989	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 112 [N=13, 8, 6]	-8.47 tender joints Standard Deviation 6.205	-13.63 tender joints Standard Deviation 6.435	-9.17 tender joints Standard Deviation 5.981	—
Change From Baseline in Tender 28-joint Count During the Extension Study Week 124 [N=2, 1, 1]	-9.00 tender joints Standard Deviation 4.243	-23.00 tender joints Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	-8.00 tender joints Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	—
Change From Baseline in Tender 28-joint Count During the Extension Study End of Study Visit [N=103, 55, 53]	-7.93 tender joints Standard Deviation 7.857	-8.43 tender joints Standard Deviation 8.331	-8.83 tender joints Standard Deviation 7.573	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=106 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=57 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=56 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 112 [N=13, 8, 6]	-33.3 scores on a scale Standard Deviation 20.38	-17.5 scores on a scale Standard Deviation 25.39	-31.7 scores on a scale Standard Deviation 38.93	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 24 [N=106, 57, 56]	-22.8 scores on a scale Standard Deviation 26.44	-24.1 scores on a scale Standard Deviation 25.69	-20.8 scores on a scale Standard Deviation 25.61	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 36 [N=100, 48, 48]	-21.7 scores on a scale Standard Deviation 29.00	-28.2 scores on a scale Standard Deviation 22.05	-24.0 scores on a scale Standard Deviation 24.13	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 48 [N=96, 43, 47]	-25.1 scores on a scale Standard Deviation 28.08	-30.6 scores on a scale Standard Deviation 21.94	-21.1 scores on a scale Standard Deviation 23.02	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 60 [N=87, 40, 42]	-26.3 scores on a scale Standard Deviation 27.09	-27.8 scores on a scale Standard Deviation 25.63	-30.0 scores on a scale Standard Deviation 23.04	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 72 [N=66, 34, 27]	-29.0 scores on a scale Standard Deviation 27.42	-35.2 scores on a scale Standard Deviation 26.06	-26.2 scores on a scale Standard Deviation 27.63	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 88 [N=43, 25, 23]	-28.5 scores on a scale Standard Deviation 30.42	-29.0 scores on a scale Standard Deviation 30.23	-32.3 scores on a scale Standard Deviation 24.84	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 100 [N=21, 13, 14]	-30.7 scores on a scale Standard Deviation 23.60	-27.6 scores on a scale Standard Deviation 26.14	-32.0 scores on a scale Standard Deviation 26.15	—
Change From Baseline in Patient's Pain Intensity During the Extension Study Week 124 [N=2, 1, 1]	-55.0 scores on a scale Standard Deviation 15.56	-17.0 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	-24.0 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	—
Change From Baseline in Patient's Pain Intensity During the Extension Study End of Study Visit [N=103, 53, 54]	-19.1 scores on a scale Standard Deviation 28.14	-21.9 scores on a scale Standard Deviation 27.19	-20.9 scores on a scale Standard Deviation 27.45	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=105 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=57 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=56 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 24 [N=105, 57, 56]	-23.2 scores on a scale Standard Deviation 26.12	-21.9 scores on a scale Standard Deviation 23.21	-18.6 scores on a scale Standard Deviation 24.42	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 36 [N=100, 48, 48]	-22.5 scores on a scale Standard Deviation 28.61	-23.8 scores on a scale Standard Deviation 23.11	-20.0 scores on a scale Standard Deviation 25.52	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 48 [N=96, 43, 47]	-25.8 scores on a scale Standard Deviation 27.92	-27.2 scores on a scale Standard Deviation 21.44	-23.6 scores on a scale Standard Deviation 25.23	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 60 [N=87, 40, 42]	-27.7 scores on a scale Standard Deviation 29.08	-24.4 scores on a scale Standard Deviation 24.23	-26.5 scores on a scale Standard Deviation 25.63	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 72 [N=66, 33, 27]	-28.6 scores on a scale Standard Deviation 24.54	-32.1 scores on a scale Standard Deviation 26.56	-24.1 scores on a scale Standard Deviation 32.14	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 88 [N=43, 25, 23]	-28.4 scores on a scale Standard Deviation 27.77	-30.9 scores on a scale Standard Deviation 25.59	-29.2 scores on a scale Standard Deviation 23.95	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 100 [N=21, 13, 14]	-34.1 scores on a scale Standard Deviation 20.69	-27.6 scores on a scale Standard Deviation 21.85	-31.9 scores on a scale Standard Deviation 24.45	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 112 [N=13, 8, 6]	-29.9 scores on a scale Standard Deviation 23.05	-28.5 scores on a scale Standard Deviation 19.01	-36.8 scores on a scale Standard Deviation 38.84	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study Week 124 [N=2, 1, 1]	-59.5 scores on a scale Standard Deviation 20.51	-20.0 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	-21.0 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	—
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study End of Study Visit [N=103, 52, 54]	-20.4 scores on a scale Standard Deviation 27.93	-19.7 scores on a scale Standard Deviation 26.29	-18.6 scores on a scale Standard Deviation 27.61	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=105 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=57 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=55 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 24 [N=105, 57, 55]	-30.9 scores on a scale Standard Deviation 23.58	-36.1 scores on a scale Standard Deviation 25.59	-36.0 scores on a scale Standard Deviation 23.94	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 36 [N=98, 48, 48]	-31.1 scores on a scale Standard Deviation 22.69	-41.6 scores on a scale Standard Deviation 18.24	-37.3 scores on a scale Standard Deviation 24.17	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 48 [N=93, 43, 47]	-34.3 scores on a scale Standard Deviation 22.60	-45.6 scores on a scale Standard Deviation 18.09	-38.8 scores on a scale Standard Deviation 24.99	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 60 [N=89, 40, 43]	-34.9 scores on a scale Standard Deviation 23.57	-41.9 scores on a scale Standard Deviation 22.92	-42.3 scores on a scale Standard Deviation 24.00	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 72 [N=66, 34, 27]	-37.7 scores on a scale Standard Deviation 25.64	-44.6 scores on a scale Standard Deviation 22.32	-43.8 scores on a scale Standard Deviation 18.34	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 88 [N=42, 25, 22]	-41.9 scores on a scale Standard Deviation 23.81	-44.8 scores on a scale Standard Deviation 19.42	-45.4 scores on a scale Standard Deviation 19.00	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 100 [N=21, 12, 13]	-45.2 scores on a scale Standard Deviation 18.56	-42.2 scores on a scale Standard Deviation 12.93	-47.6 scores on a scale Standard Deviation 17.04	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 112 [N=13, 8, 6]	-45.2 scores on a scale Standard Deviation 22.11	-51.4 scores on a scale Standard Deviation 13.11	-29.0 scores on a scale Standard Deviation 33.15	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study Week 124 [N=2, 1, 1]	-54.5 scores on a scale Standard Deviation 0.71	-49.0 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	-39.0 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	—
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study End of Study Visit [N=102, 53, 53]	-25.6 scores on a scale Standard Deviation 27.23	-29.7 scores on a scale Standard Deviation 25.95	-31.8 scores on a scale Standard Deviation 29.28	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=107 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=58 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=56 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 24 [N=106, 58, 56]	-0.241 scores on a scale Standard Deviation 0.5430	-0.304 scores on a scale Standard Deviation 0.4895	-0.239 scores on a scale Standard Deviation 0.5142	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 36 [N=99, 49, 48]	-0.266 scores on a scale Standard Deviation 0.5418	-0.347 scores on a scale Standard Deviation 0.5066	-0.302 scores on a scale Standard Deviation 0.5511	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 48 [N=96, 44, 47]	-0.322 scores on a scale Standard Deviation 0.5446	-0.324 scores on a scale Standard Deviation 0.4988	-0.293 scores on a scale Standard Deviation 0.5375	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 60 [N=86, 40, 42]	-0.347 scores on a scale Standard Deviation 0.5552	-0.419 scores on a scale Standard Deviation 0.5819	-0.425 scores on a scale Standard Deviation 0.6047	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 72 [N=65, 34, 27]	-0.398 scores on a scale Standard Deviation 0.6047	-0.441 scores on a scale Standard Deviation 0.5849	-0.449 scores on a scale Standard Deviation 0.6338	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 88 [N=44, 25, 23]	-0.472 scores on a scale Standard Deviation 0.5985	-0.440 scores on a scale Standard Deviation 0.5218	-0.451 scores on a scale Standard Deviation 0.5823	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 100 [N=21, 13, 14]	-0.613 scores on a scale Standard Deviation 0.5504	-0.298 scores on a scale Standard Deviation 0.4692	-0.563 scores on a scale Standard Deviation 0.7448	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 112 [N=13, 8, 6]	-0.538 scores on a scale Standard Deviation 0.5410	-0.406 scores on a scale Standard Deviation 0.6640	-0.542 scores on a scale Standard Deviation 0.7100	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study Week 124 [N=2, 1, 1]	-0.938 scores on a scale Standard Deviation 0.6187	-0.625 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	-1.250 scores on a scale Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	—
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study End of Study Visit [N=101, 54, 54]	-0.260 scores on a scale Standard Deviation 0.6051	-0.322 scores on a scale Standard Deviation 0.5724	-0.291 scores on a scale Standard Deviation 0.6259	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=106 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=58 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=55 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 24 [N=106, 58, 55]	-4.82 mg/L Standard Deviation 17.914	-6.45 mg/L Standard Deviation 14.556	-9.59 mg/L Standard Deviation 18.388	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 36 [N=97, 49, 50]	-7.76 mg/L Standard Deviation 16.771	-4.57 mg/L Standard Deviation 14.393	0.50 mg/L Standard Deviation 71.610	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 48 [N=95, 44, 47]	-5.61 mg/L Standard Deviation 22.335	-4.63 mg/L Standard Deviation 13.521	-11.04 mg/L Standard Deviation 20.261	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 60 [N=88, 40, 43]	-6.93 mg/L Standard Deviation 21.160	0.49 mg/L Standard Deviation 47.139	-7.04 mg/L Standard Deviation 18.638	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 72 [N=63, 33, 26]	-9.02 mg/L Standard Deviation 18.067	-5.29 mg/L Standard Deviation 15.219	-7.70 mg/L Standard Deviation 18.221	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 88 [N=44, 24, 22]	-8.45 mg/L Standard Deviation 19.060	-7.31 mg/L Standard Deviation 13.035	-7.65 mg/L Standard Deviation 18.098	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 100 [N=21, 14, 12]	-7.29 mg/L Standard Deviation 12.850	-2.74 mg/L Standard Deviation 17.273	-10.74 mg/L Standard Deviation 24.539	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 112 [N=13, 9, 6]	-5.75 mg/L Standard Deviation 10.438	-1.80 mg/L Standard Deviation 18.838	-19.33 mg/L Standard Deviation 35.567	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study Week 124 [N=2, 1, 1]	4.95 mg/L Standard Deviation 13.364	-22.70 mg/L Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	0.20 mg/L Standard Deviation NA Mean based on 1 participant. Standard deviation can not be calculated.	—
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study End of Study Visit [N=101, 57, 52]	-7.01 mg/L Standard Deviation 17.934	-2.94 mg/L Standard Deviation 15.735	-9.74 mg/L Standard Deviation 20.766	—

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 36, 48, 60, 72 and 88.

Population: The Extension Study ITT population. At each timepoint, only patients with a value at both Baseline and that timepoint are included (N).

Outcome measures

Outcome measures
Measure	Canakinumab 600 mg IV + 300 mg q2wk n=105 Participants Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.	Canakinumab 300 mg q2wk n=58 Participants Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Canakinumab 150 mg q4wk n=54 Participants Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.	Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study Week 24 [N=105, 58, 54]	-14.9 mm/hr Standard Deviation 17.31	-18.3 mm/hr Standard Deviation 14.96	-16.8 mm/hr Standard Deviation 17.10	—
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study Week 36 [N=95, 46, 48]	-14.5 mm/hr Standard Deviation 18.99	-13.6 mm/hr Standard Deviation 19.09	-11.3 mm/hr Standard Deviation 25.94	—
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study Week 48 [N=91, 42, 47]	-15.6 mm/hr Standard Deviation 20.13	-16.6 mm/hr Standard Deviation 13.44	-17.0 mm/hr Standard Deviation 18.81	—
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study Week 60 [N=85, 39, 43]	-17.2 mm/hr Standard Deviation 19.07	-15.8 mm/hr Standard Deviation 19.08	-16.7 mm/hr Standard Deviation 19.09	—
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study Week 72 [N=64, 34, 26]	-18.6 mm/hr Standard Deviation 17.83	-15.3 mm/hr Standard Deviation 16.39	-14.1 mm/hr Standard Deviation 23.10	—
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study Week 88 [N=42, 24, 23]	-19.7 mm/hr Standard Deviation 17.46	-13.5 mm/hr Standard Deviation 16.38	-13.3 mm/hr Standard Deviation 20.89	—
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study End of Study Visit [N=98, 55, 55]	-14.9 mm/hr Standard Deviation 18.09	-14.0 mm/hr Standard Deviation 17.51	-15.9 mm/hr Standard Deviation 18.10	—

Adverse Events

ACZ885 600mg iv + 300mg sc q2wk

Serious events: 11 serious events

Other events: 42 other events

Deaths: 0 deaths

ACZ885 300mg sc q2wk

Serious events: 16 serious events

Other events: 38 other events

Deaths: 0 deaths

ACZ885 150mg sc q4wk

Serious events: 12 serious events

Other events: 39 other events

Deaths: 0 deaths

Placebo

Serious events: 16 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ACZ885 600mg iv + 300mg sc q2wk n=71 participants at risk ACZ885 600mg iv + 300mg sc q2wk	ACZ885 300mg sc q2wk n=64 participants at risk ACZ885 300mg sc q2wk	ACZ885 150mg sc q4wk n=69 participants at risk ACZ885 150mg sc q4wk	Placebo n=70 participants at risk Placebo
Blood and lymphatic system disorders Anaemia	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Cardiac disorders Atrial fibrillation	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Cardiac disorders Tachyarrhythmia	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Ear and labyrinth disorders Sudden hearing loss	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Eye disorders Cataract	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Gastrointestinal disorders Abdominal hernia obstructive	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Gastrointestinal disorders Ascites	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Gastrointestinal disorders Colitis	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Gastrointestinal disorders Diarrhoea	1.4% 1/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Gastrointestinal disorders Duodenal ulcer	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Gastrointestinal disorders Dyspepsia	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/71	0.00% 0/64	1.4% 1/69	1.4% 1/70
Gastrointestinal disorders Gastritis	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Gastrointestinal disorders Intestinal perforation	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Gastrointestinal disorders Large intestine perforation	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
General disorders Chest pain	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
General disorders Malaise	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Infections and infestations Abscess limb	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Infections and infestations Appendicitis	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Infections and infestations Arthritis bacterial	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Infections and infestations Bronchitis	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Infections and infestations Cellulitis	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Infections and infestations Chronic sinusitis	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Infections and infestations Device related infection	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Infections and infestations Diverticulitis	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Infections and infestations Erysipelas	1.4% 1/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Infections and infestations Infected epidermal cyst	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Infections and infestations Meningitis	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Infections and infestations Respiratory tract infection	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Infections and infestations Soft tissue infection	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Infections and infestations Subcutaneous abscess	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Infections and infestations Urinary tract infection	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Infections and infestations Urosepsis	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Infections and infestations Wound infection	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Injury, poisoning and procedural complications Epicondylitis	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Injury, poisoning and procedural complications Radius fracture	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Injury, poisoning and procedural complications Seroma	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Investigations Tumour marker increased	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Metabolism and nutrition disorders Dehydration	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Musculoskeletal and connective tissue disorders Hand deformity	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/71	1.6% 1/64	2.9% 2/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	1.4% 1/71	1.6% 1/64	1.4% 1/69	4.3% 3/70
Musculoskeletal and connective tissue disorders Rheumatoid nodule	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiomyolipoma	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma metastatic	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Nervous system disorders Cervical myelopathy	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Nervous system disorders Ischaemic stroke	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Nervous system disorders Transient ischaemic attack	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Psychiatric disorders Depression	0.00% 0/71	1.6% 1/64	0.00% 0/69	1.4% 1/70
Renal and urinary disorders Renal colic	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Reproductive system and breast disorders Ovarian cyst	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Reproductive system and breast disorders Uterine haemorrhage	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/71	0.00% 0/64	1.4% 1/69	0.00% 0/70
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Vascular disorders Deep vein thrombosis	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Vascular disorders Hypertension	0.00% 0/71	1.6% 1/64	1.4% 1/69	0.00% 0/70
Vascular disorders Peripheral arterial occlusive disease	1.4% 1/71	0.00% 0/64	0.00% 0/69	0.00% 0/70
Vascular disorders Thromboangiitis obliterans	0.00% 0/71	0.00% 0/64	0.00% 0/69	1.4% 1/70
Vascular disorders Thrombophlebitis	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70
Vascular disorders Venous thrombosis limb	0.00% 0/71	1.6% 1/64	0.00% 0/69	0.00% 0/70

Other adverse events

Other adverse events
Measure	ACZ885 600mg iv + 300mg sc q2wk n=71 participants at risk ACZ885 600mg iv + 300mg sc q2wk	ACZ885 300mg sc q2wk n=64 participants at risk ACZ885 300mg sc q2wk	ACZ885 150mg sc q4wk n=69 participants at risk ACZ885 150mg sc q4wk	Placebo n=70 participants at risk Placebo
Gastrointestinal disorders Diarrhoea	7.0% 5/71	9.4% 6/64	4.3% 3/69	7.1% 5/70
Gastrointestinal disorders Dyspepsia	1.4% 1/71	1.6% 1/64	5.8% 4/69	0.00% 0/70
Gastrointestinal disorders Nausea	5.6% 4/71	7.8% 5/64	1.4% 1/69	5.7% 4/70
General disorders Fatigue	4.2% 3/71	4.7% 3/64	4.3% 3/69	7.1% 5/70
General disorders Oedema peripheral	4.2% 3/71	6.2% 4/64	5.8% 4/69	8.6% 6/70
Infections and infestations Bronchitis	8.5% 6/71	9.4% 6/64	5.8% 4/69	4.3% 3/70
Infections and infestations Gastroenteritis	8.5% 6/71	3.1% 2/64	0.00% 0/69	5.7% 4/70
Infections and infestations Influenza	1.4% 1/71	3.1% 2/64	5.8% 4/69	4.3% 3/70
Infections and infestations Nasopharyngitis	19.7% 14/71	18.8% 12/64	17.4% 12/69	14.3% 10/70
Infections and infestations Sinusitis	7.0% 5/71	0.00% 0/64	1.4% 1/69	1.4% 1/70
Infections and infestations Upper respiratory tract infection	8.5% 6/71	12.5% 8/64	7.2% 5/69	11.4% 8/70
Infections and infestations Urinary tract infection	9.9% 7/71	7.8% 5/64	4.3% 3/69	5.7% 4/70
Musculoskeletal and connective tissue disorders Arthralgia	8.5% 6/71	4.7% 3/64	7.2% 5/69	8.6% 6/70
Musculoskeletal and connective tissue disorders Back pain	2.8% 2/71	6.2% 4/64	4.3% 3/69	5.7% 4/70
Musculoskeletal and connective tissue disorders Myalgia	2.8% 2/71	3.1% 2/64	5.8% 4/69	1.4% 1/70
Musculoskeletal and connective tissue disorders Osteoarthritis	5.6% 4/71	6.2% 4/64	1.4% 1/69	0.00% 0/70
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	4.2% 3/71	12.5% 8/64	8.7% 6/69	10.0% 7/70
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/71	4.7% 3/64	1.4% 1/69	5.7% 4/70
Nervous system disorders Dizziness	2.8% 2/71	3.1% 2/64	1.4% 1/69	5.7% 4/70
Nervous system disorders Headache	11.3% 8/71	6.2% 4/64	5.8% 4/69	5.7% 4/70
Respiratory, thoracic and mediastinal disorders Cough	4.2% 3/71	7.8% 5/64	7.2% 5/69	7.1% 5/70
Skin and subcutaneous tissue disorders Rash	0.00% 0/71	1.6% 1/64	5.8% 4/69	1.4% 1/70
Vascular disorders Hypertension	4.2% 3/71	9.4% 6/64	4.3% 3/69	2.9% 2/70

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER