Long-term Efficacy, Safety and Tolerability of ACZ885 in Patients With Rheumatoid Arthritis

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00554606
• Collaborator: (none)
• Enrollment: 115
• Locations: 51
• Arm: 1
• Actual Duration (Months): 22.1
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will assess the long-term safety and tolerability of ACZ885 in patients with rheumatoid arthritis, as well as long-term efficacy, long-term preservation and/or improvement of joint structure and bone mineral density, and long term maintenance of health-related quality of life.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Canakinumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 115 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 54-week, Phase II, Multi-center, Open-label Extension Study to Evaluate the Efficacy, Safety and Tolerability of ACZ885 (Anti-interleukin-1B Monoclonal Antibody) in Patients With Rheumatoid Arthritis
• Actual Study Start Date: Oct 11, 2007
• Actual Primary Completion Date: Aug 13, 2009
• Actual Study Completion Date: Aug 13, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canakinumab Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.	Drug: Canakinumab; Canakinumab; Other Names: ACZ885

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events and Serious Adverse Events [From start of the study up to End Of Study (Week 60)]

   Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

Secondary Outcome Measures

1. Percentage of Participants Who Achieved American College of Rheumatology Response 20 (ACR20) [Baseline Up to End Of Study (up to week 60)]

   ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

2. Percentage of Participants Who Achieved American College of Rheumatology Response 50 (ACR50) [Baseline Up to End Of Study (up to week 60)]

   ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

3. Percentage of Participants Who Achieved American College of Rheumatology Response 70 (ACR70) [Baseline Up to End Of Study (up to week 60)]

   ACR70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 70% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

4. Percentage of Participants Who Achieved American College of Rheumatology Response 90 (ACR90) [Baseline Up to End Of Study (up to week 60)]

   ACR90 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 90% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

5. Percentage of Participants Achieving Clinical Remission Based on Disease Activity Score (DAS) 28 and Simplified Disease Activity Index (SDAI) [Baseline Up to End Of Study (up to week 60)]

   At each visit (including baseline) the DAS28 and SDAI variables were derived using the following formulas: DAS28 = 0.56*√ (tender28) + 0.28 * √ (swollen28) + 0.36 * loge(CRP+1) + 0.014*PGDA+ 0.96; SDAI = tender28 + swollen28 + CRP + (PGDA / 10) + (EGDA / 10) where tender28 is the tender 28-joint count, swollen28 is the swollen 28-joint count, CRP is C-reactive protein, PGDA is the patient's global assessment of disease activity and EGDA is the physician's global assessment of disease activity. The Number of Participants in clinical remission is defined as the DAS28 ≤ (less than or equal to) 2.6 or SDAI ≤ (less than or equal to) to3.3.

6. Change From Baseline in ACR Component : Swollen Joint Count Through Week 54 [Baseline Up to End Of Study (up to week 60)]

   Synovial fluid and/or soft tissue swelling but not bony overgrowth represents a positive result for swollen joint count. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. Whenever possible, the same evaluator performed these assessments at all visits. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., S) was less than 28, the number of swollen joints (e.g., s) was scaled up proportionately (i.e., 28*(s/S)).

7. Change From Baseline in ACR Component : Tender Joint Count Through Week 54 [Baseline Up to End Of Study (up to week 60)]

   The ACR tender joint count (28 joints) was done by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., T) was less than 28, the number of tender joints (e.g., t) was scaled up proportionately (i.e., 28*(t/T)).

8. Change From Baseline in ACR Component: Patient's Assessment of Pain Activity Through Week 54 [Baseline Up to End Of Study (up to week 60)]

   ACR components included patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain).

9. Change From Baseline in ACR Component:- Patient's Global Assessment of Disease Activity Through Week 24 [Baseline Up to End Of Study (up to week 60)]

   ACR component included patient's global assessment (PtGA) of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor).

10. Change From Baseline in ACR Component : Physician's Global Assessment of Disease Activity Through Week 54 [Baseline Up to End Of Study (up to week 60)]

    ACR component included physician's global assessment (PGA) of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis).

11. Change From Baseline in ACR Component : C-reactive Protein (CRP) Through Week 54 [Baseline Up to End Of Study (up to week 60)]

    Blood for this assessment was obtained in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. Assessment was performed by the central laboratory.

12. Core Study Change From Baseline in Edema, Erosion and Synovitis Score Was Assessed at Week 18 [Baseline, Week 18]

    The MRI scan was scored according to OMERACT RAMRIS system. Erosions were scored on a scale of 0-10 per site, the scale is 0-10, based on the proportion of eroded bone compared to the "assessed bone volume", judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2; 11-20%, etc. For long bones, the "assessed bone volume" is from the articular surface (or its best estimated position if absent) to a depth of 1 cm, and in carpal bones it is the whole bone. Edema were scored on a scale of 0-10 per site, the scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%; and Synovitis on a scale of 0-3 per site, the scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.

13. Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Erosion Score at Week 18 [Baseline, Week 18]

    Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.

14. Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Joint Narrowing Score at Week 18 [Baseline, Week 18]

    Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.

15. Core Study BMD of Total Lumbar Spine, Hip and Hand Was Assessed by DXA at Week 18 [Baseline, Week 18]

    Bone Mineral Density was measured by dual-energy X-ray absorptiometry (DXA) of the hand with the most swollen wrist (determined at baseline by the investigator site), lumbosacral (LS) spine and hip, in selected study sites. The reading of the DXA scans were performed centrally, by an experienced independent reader who was blinded to clinical details and MRI findings.

16. Number of Subjects With Long-term Immunogenicity [Baseline Up to End Of Study (up to week 60)]

    Anti-ACZ885 antibodies concentrations were assessed in serum. All blood samples were taken by direct venipuncture in a forearm vein. Immunogenicity was analyzed by BIAcore technology. immunogenicity was categorized as NO (no immunogenicity), BLQ (positive immunogenicity < LLOQ (not quantifiable)), and ALQ (positive immunogenicity > LLOQ (quantifiable).

17. Pharmacokinetic (PK) of ACZ885: Systemic Clearance From Serum Following Intravenous Administration (CL) in Participants [Pre dose at Day 1, Pre dose at week 6, 12, 18, 24, 30, 36, 42, 48, follow up and at study completion (week 60)]

    The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.

18. Pharmacokinetic (PK) of ACZ885: Volume Distribution From Serum Following Intravenous Administration (CL) in Participants [Pre dose at Day 1, Pre dose at week 6, 12, 18, 24, 30, 36, 42, 48, follow up and at study completion (week 60)]

    The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.

19. Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Physical Component) [Baseline Up to End Of Study (up to week 60)]

    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.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.

20. Health-Related Quality of Life (HRQoL) Accessed by Health Assessment Questionnaire (HAQ) Score [Baseline Up to End Of Study (up to week 60)]

    HAQ assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3 where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question.A decrease from baseline indicates improvement for HAQ-DI. The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 to 3, with higher scores indicating greater disability.

21. Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Mental Component) [Baseline Up to End Of Study (up to week 60)]

    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.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients (male and non-pregnant, non-lactating females) who completed the core CACZ885A2204, CACZ885A2206, or CACZ885A2207 study without serious or severe drug-related adverse effects may enter the extension study upon signing informed consent

Exclusion Criteria:

• Patients for whom continued treatment in the extension is not considered appropriate by the treating physician.

• Patients who were non-compliant or who demonstrated a major protocol violation in the core study.

• Patients who did not complete / discontinued from the core study.

• Patients with drug related serious adverse events or severe adverse events.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	Huntsville	Alabama	United States	35801
2	Novartis Investigator Site	Tuscaloosa	Alabama	United States	35406
3	Novartis Investigator Site	Paradise Valley	Arizona	United States	85253
4	Novartis Investigator Site	Trumbull	Connecticut	United States	06611
5	Novartis Investigator Site	Jacksonville	Florida	United States	32216
6	Novartis Investigator Site	South Miami	Florida	United States	33143
7	Novartis Investigator Site	Tamarac	Florida	United States	33321
8	Novartis Investigator Site	Rockford	Illinois	United States	61107
9	Novartis Investigator Site	Urbandale	Indiana	United States	50322
10	Novartis Investigator Site	Richmond Heights	Missouri	United States	63117
11	Novartis Investigator Site	Omaha	Nebraska	United States	68114
12	Novartis Investigator Site	Reno	Nevada	United States	89502
13	Novartis Investigator Site	Tulsa	Oklahoma	United States	74104
14	Novartis Investigator Site	Austin	Texas	United States	78704
15	Novartis Investigator Site	Carrollton	Texas	United States	75007
16	Novartis Investigator Site	Dallas	Texas	United States	75246
17	Novartis Investigator Site	Fort Worth	Texas	United States	75246
18	Novartis Investigator Site	Mesquite	Texas	United States	75150
19	Novartis Investigator Site	Arlington	Virginia	United States	22205
20	Novartis Investigator Site	Spokane	Washington	United States	99204
21	Novartis Investigator Site	Antwerpen		Belgium
22	Novartis Investigator Site	Diepenbeek		Belgium
23	Novartis Investigator Site	Liege		Belgium
24	Novartis Investigator Site	Berlin		Germany
25	Novartis Investigator Site	Hamburg		Germany
26	Novartis Investigator Site	Hannover		Germany
27	Novartis Investigator Site	Ratingen		Germany
28	Novartis Investigator Site	Sendenhorst		Germany
29	Novartis Investigator Site	Wiesbaden		Germany
30	Novartis Investigator Site	Arenzano	GE	Italy
31	Novartis Investigator Site	Valeggio sul Mincio	VR	Italy
32	Novartis Investigator Site	Genova		Italy
33	Novartis Investigator Site	Padova		Italy
34	Novartis Investigator Site	Leeuwarden		Netherlands
35	Novartis Investigator Site	Leiden		Netherlands
36	Novartis Investigator Site	Venlo		Netherlands
37	Novartis Investigator Site	Moscow		Russian Federation
38	Novartis Investigator Site	Yaroslavl		Russian Federation
39	Novartis Investigator Site	Yekaterinburg		Russian Federation
40	Novartis Investigator Site	Alicante		Spain
41	Novartis Investigator Site	Barcelona		Spain
42	Novartis Investigator Site	Bilbao		Spain
43	Novartis Investigator Site	Madrid		Spain
44	Novartis Investigator Site	Santiago de Compostela		Spain
45	Novartis Investigator Site	Sevilla		Spain
46	Novartis Investigator Site	Valencia		Spain
47	Novartis Investigator Site	Basel		Switzerland
48	Novartis Investigator Site	Zurich		Switzerland
49	Novartis Investigator Site	Istanbul		Turkey
50	Novartis Investigator Site	Izmir		Turkey
51	Novartis Investigator Site	Sihhiye/Ankara		Turkey

Sponsors and Collaborators

• Novartis

Investigators

• Principal Investigator: NOVARTIS, Novartis investigator site

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00554606
• Other Study ID Numbers: CACZ885A2211
• First Posted: Nov 7, 2007
• Last Update Posted: Jul 9, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Novartis: Rheumatoid Arthritis; Anti-interleukin-1 beta; ACZ885
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Pre-assignment Detail	A total of 115 participants were enrolled in the trial (56 from core trial CACZ885A2204, 8 from CACZ885A2206, and 51 from CACZ885A2207).

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Period Title: Overall Study
STARTED	115
COMPLETED	30
NOT COMPLETED	85

Baseline Characteristics

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Overall Participants	115
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.3 (13.16)
Sex: Female, Male (Count of Participants)
Female	93 80.9%
Male	22 19.1%
Race/Ethnicity, Customized (Count of Participants)
White	109 94.8%
Black	2 1.7%
Asian	2 1.7%
Native American	1 0.9%
Other	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events
Description	Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Time Frame	From start of the study up to End Of Study (Week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Adverse Events	91 79.1%
Death	1 0.9%
Serious Adverse Events	8 7%
Discontinued due to Serious Adverse Events	3 2.6%

2. Secondary Outcome

Title	Percentage of Participants Who Achieved American College of Rheumatology Response 20 (ACR20)
Description	ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	48.7 42.3%
Day 1	49.6 43.1%
Week 6	57.4 49.9%
Week 12	53.3 46.3%
Week 18	58.7 51%
Week 24	54.2 47.1%
Week 30	61.4 53.4%
WeeK 36	52.7 45.8%
Week 42	57.1 49.7%
Week 48	53.3 46.3%
Week 54 (Follow-Up)	41.7 36.3%
End of Study	45.9 39.9%

3. Secondary Outcome

Title	Percentage of Participants Who Achieved American College of Rheumatology Response 50 (ACR50)
Description	ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	23.5 20.4%
Day 1	23.5 20.4%
Week 6	25.0 21.7%
Week 12	30.8 26.8%
Week 18	26.0 22.6%
Week 24	32.3 28.1%
Week 30	32.5 28.3%
Week 36	35.1 30.5%
Week 42	38.8 33.7%
Week 48	28.9 25.1%
End of Study	26.1 22.7%

4. Secondary Outcome

Title	Percentage of Participants Who Achieved American College of Rheumatology Response 70 (ACR70)
Description	ACR70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 70% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	12.2 10.6%
Day 1	11.3 9.8%
Week 6	13.0 11.3%
Week 12	13.1 11.4%
Week 18	14.4 12.5%
Week 24	16.7 14.5%
Week 30	18.1 15.7%
Week 36	20.3 17.7%
Week 42	26.5 23%
Week 48	13.3 11.6%
Week 54 (Follow-Up)	14.6 12.7%
End of Study	15.3 13.3%

5. Secondary Outcome

Title	Percentage of Participants Who Achieved American College of Rheumatology Response 90 (ACR90)
Description	ACR90 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 90% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all subjects that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	2.6 2.3%
Day 1	2.6 2.3%
Week 6	2.8 2.4%
Week 12	2.8 2.4%
Week 18	1.9 1.7%
Week 24	5.2 4.5%
Week 30	3.6 3.1%
Week 36	6.8 5.9%
Week 42	8.2 7.1%
Week 48	6.7 5.8%
Week 54 (Follow-Up)	10.4 9%
End of Study	5.4 4.7%

6. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission Based on Disease Activity Score (DAS) 28 and Simplified Disease Activity Index (SDAI)
Description	At each visit (including baseline) the DAS28 and SDAI variables were derived using the following formulas: DAS28 = 0.56*√ (tender28) + 0.28 * √ (swollen28) + 0.36 * loge(CRP+1) + 0.014*PGDA+ 0.96; SDAI = tender28 + swollen28 + CRP + (PGDA / 10) + (EGDA / 10) where tender28 is the tender 28-joint count, swollen28 is the swollen 28-joint count, CRP is C-reactive protein, PGDA is the patient's global assessment of disease activity and EGDA is the physician's global assessment of disease activity. The Number of Participants in clinical remission is defined as the DAS28 ≤ (less than or equal to) 2.6 or SDAI ≤ (less than or equal to) to3.3.
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	11.3 9.8%
Day 1	14.8 12.9%
Week 6	16.7 14.5%
Week 12	18.7 16.3%
Week 18	19.2 16.7%
Week 24	20.8 18.1%
Week 30	24.1 21%
Week 36	18.9 16.4%
Week 42	32.7 28.4%
Week 48	17.8 15.5%
Week 54 (Follow-Up)	27.7 24.1%
End of study	18.2 15.8%

7. Secondary Outcome

Title	Change From Baseline in ACR Component : Swollen Joint Count Through Week 54
Description	Synovial fluid and/or soft tissue swelling but not bony overgrowth represents a positive result for swollen joint count. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. Whenever possible, the same evaluator performed these assessments at all visits. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., S) was less than 28, the number of swollen joints (e.g., s) was scaled up proportionately (i.e., 28*(s/S)).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	6.0 (5.10)
Day 1	6.5 (5.53)
Week 6	5.8 (5.65)
Week 12	5.2 (5.16)
Week 18	5.0 (5.18)
Week 24	4.4 (4.35)
Week 30	3.9 (4.37)
Week 36	3.5 (4.65)
Week 42	3.8 (4.60)
Week 48	4.4 (4.99)
Week 54 (Follow-Up)	3.9 (5.22)
End of Study	5.1 (5.18)

8. Secondary Outcome

Title	Change From Baseline in ACR Component : Tender Joint Count Through Week 54
Description	The ACR tender joint count (28 joints) was done by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., T) was less than 28, the number of tender joints (e.g., t) was scaled up proportionately (i.e., 28*(t/T)).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	9.3 (7.70)
Day 1	9.5 (8.11)
Week 6	8.7 (7.70)
Week 12	7.9 (7.17)
Week 18	7.7 (7.15)
Week 24	7.1 (7.40)
Week 30	6.9 (7.54)
Week 36	6.9 (7.19)
Week 42	3.8 (6.12)
Week 48	4.9 (6.33)
Week 54 (Follow-Up)	5.9 (7.11)
End of Study	7.6 (7.25)

9. Secondary Outcome

Title	Change From Baseline in ACR Component: Patient's Assessment of Pain Activity Through Week 54
Description	ACR components included patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	42.3 (21.93)
Day 1	41.2 (21.60)
Week 6	37.8 (21.16)
Week 12	37.1 (21.21)
Week 18	39.4 (21.35)
Week 24	36.8 (20.55)
Week 30	36.3 (21.13)
Week 36	36.5 (23.01)
Week 42	32.5 (21.11)
Week 48	33.0 (21.24)
Week 54 (Follow-Up)	35.9 (22.12)
End of Study	40.1 (20.60)

10. Secondary Outcome

Title	Change From Baseline in ACR Component:- Patient's Global Assessment of Disease Activity Through Week 24
Description	ACR component included patient's global assessment (PtGA) of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	45.0 (23.05)
Day 1	44.1 (21.96)
Week 6	40.3 (22.02)
Week 12	39.9 (21.01)
Week 18	42.0 (20.89)
Week 24	38.3 (21.04)
Week 30	36.6 (21.97)
Week 36	39.9 (21.70)
Week 42	31.2 (21.40)
Week 48	37.6 (23.08)
Week 54 (Follow-Up)	38.4 (23.99)
End of Study	42.0 (21.77)

11. Secondary Outcome

Title	Change From Baseline in ACR Component : Physician's Global Assessment of Disease Activity Through Week 54
Description	ACR component included physician's global assessment (PGA) of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	37.0 (23.11)
Day 1	38.7 (23.09)
Week 6	34.1 (22.70)
Week 12	33.0 (21.82)
Week 18	33.7 (22.06)
Week 24	27.8 (20.25)
Week 30	26.0 (16.79)
Week 36	24.6 (16.35)
Week 42	21.3 (17.25)
Week 48	23.3 (18.10)
Week 54 (Follow-Up)	27.6 (23.70)
End of Study	32.7 (22.88)

12. Secondary Outcome

Title	Change From Baseline in ACR Component : C-reactive Protein (CRP) Through Week 54
Description	Blood for this assessment was obtained in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. Assessment was performed by the central laboratory.
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	14.42 (22.406)
Day 1	15.30 (26.827)
Week 6	10.38 (16.717)
Week 12	10.10 (19.355)
Week 18	9.99 (16.948)
Week 24	8.35 (16.413)
Week 30	8.03 (14.065)
Week 36	6.49 (10.146)
Week 42	5.71 (10.577)
Week 48	6.72 (11.545)
Week 54 (Follow-Up)	6.71 (12.611)
End of Study	10.74 (22.520)

13. Secondary Outcome

Title	Core Study Change From Baseline in Edema, Erosion and Synovitis Score Was Assessed at Week 18
Description	The MRI scan was scored according to OMERACT RAMRIS system. Erosions were scored on a scale of 0-10 per site, the scale is 0-10, based on the proportion of eroded bone compared to the "assessed bone volume", judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2; 11-20%, etc. For long bones, the "assessed bone volume" is from the articular surface (or its best estimated position if absent) to a depth of 1 cm, and in carpal bones it is the whole bone. Edema were scored on a scale of 0-10 per site, the scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%; and Synovitis on a scale of 0-3 per site, the scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.
Time Frame	Baseline, Week 18

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug. Here, number of participants (N) analyzed included all participants who were evaluable for this outcome measure and number analyzed (n) included all participants who were evaluable for the specified categories.

Arm/Group Title	Canakinumab (ACZ885) (Core Trial CACZ885A2204)	Non- ACZ885 ( (Core Trial CACZ885A2204))
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1, 15 continuing every 4 weeks up to week 26 in the core trial CACZ885A2204.	Participant who did not receive ACZ885 (Canakinumab) in the core trial CACZ885A2204.
Measure Participants	32	15
Edema Score	0	-0.043
Erosion Score	0	0
Synovitis Score	-0.143	-0.714

14. Secondary Outcome

Title	Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Erosion Score at Week 18
Description	Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Time Frame	Baseline, Week 18

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug. Here, number of participants analyzed (N) included all participants who were evaluable for this outcome measure.

Arm/Group Title	Canakinumab (ACZ885) (Core Trial CACZ885A2204)	Non- ACZ885 ( (Core Trial CACZ885A2204))
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1, 15 continuing every 4 weeks up to week 26 in the core trial CACZ885A2204.	Participant who did not receive ACZ885 (Canakinumab) in the core trial CACZ885A2204.
Measure Participants	33	16
Left Hand	0	0
Right Hand	0	0
Left Foot	0	0
Right Foot	0	0

15. Secondary Outcome

Title	Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Joint Narrowing Score at Week 18
Description	Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Time Frame	Baseline, Week 18

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment. Here, N (number of participants analyzed) included all participants who were evaluable for this outcome measure.

Arm/Group Title	Canakinumab (ACZ885) (Core Trial CACZ885A2204)	Non- ACZ885 ( (Core Trial CACZ885A2204))
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1, 15 continuing every 4 weeks up to week 26 in the core trial CACZ885A2204.	Participant who did not receive ACZ885 (Canakinumab) in the core trial CACZ885A2204.
Measure Participants	33	16
Left Hand	0	0
Right Hand	0	0
Left Foot	0	0
Right Foot	0	0

16. Secondary Outcome

Title	Core Study BMD of Total Lumbar Spine, Hip and Hand Was Assessed by DXA at Week 18
Description	Bone Mineral Density was measured by dual-energy X-ray absorptiometry (DXA) of the hand with the most swollen wrist (determined at baseline by the investigator site), lumbosacral (LS) spine and hip, in selected study sites. The reading of the DXA scans were performed centrally, by an experienced independent reader who was blinded to clinical details and MRI findings.
Time Frame	Baseline, Week 18

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug. Number of participants analyzed signifies those who were evaluable for the assessment. Here, N (number of participants analyzed) included all participants who were evaluable for this outcome measure.

Arm/Group Title	Canakinumab (ACZ885) (Core Trial CACZ885A2204)	Non- ACZ885 ( (Core Trial CACZ885A2204))
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1, 15 continuing every 4 weeks up to week 26 in the core trial CACZ885A2204.	Participant who did not receive ACZ885 (Canakinumab) in the core trial CACZ885A2204.
Measure Participants	4	1
AP lumbar spine L1- L4	1.1650 (0.36399)	1.1760
Total Hip	0.9000 (0.32558)	0.8570
Total Hand	0.3295 (0.09726)	0.4280

17. Secondary Outcome

Title	Number of Subjects With Long-term Immunogenicity
Description	Anti-ACZ885 antibodies concentrations were assessed in serum. All blood samples were taken by direct venipuncture in a forearm vein. Immunogenicity was analyzed by BIAcore technology. immunogenicity was categorized as NO (no immunogenicity), BLQ (positive immunogenicity < LLOQ (not quantifiable)), and ALQ (positive immunogenicity > LLOQ (quantifiable).
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set was defined as all participants that received at least one dose of study drug (in this extension) with at least one post-baseline safety assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline - No immunogenicity	108 93.9%
Baseline - BLQ	0 0%
Baseline - ALQ	1 0.9%
DAY 1 - No immunogenicity	94 81.7%
DAY 1 - BLQ	0 0%
DAY 1 - ALQ	0 0%
WEEK 6 - No immunogenicity	1 0.9%
WEEK 6 - BLQ	0 0%
WEEK 6 - ALQ	0 0%
WEEK 12 - No immunogenicity	89 77.4%
WEEK 12 - BLQ	0 0%
WEEK 12 - ALQ	0 0%
WEEK 24 - No immunogenicity	73 63.5%
WEEK 24 - BLQ	0 0%
WEEK 24 - ALQ	0 0%
WEEK 36 - No immunogenicity	46 40%
WEEK 36 - BLQ	0 0%
WEEK 36 - ALQ	0 0%
WEEK 48 - No immunogenicity	21 18.3%
WEEK 48 - BLQ	0 0%
WEEK 48 - ALQ	0 0%
End of study - No immunogenicity	93 80.9%
End of study - BLQ	0 0%
End of study - ALQ	0 0%

18. Secondary Outcome

Title	Pharmacokinetic (PK) of ACZ885: Systemic Clearance From Serum Following Intravenous Administration (CL) in Participants
Description	The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.
Time Frame	Pre dose at Day 1, Pre dose at week 6, 12, 18, 24, 30, 36, 42, 48, follow up and at study completion (week 60)

Outcome Measure Data

Analysis Population Description

The PK set consisted of all participant who received at least one dose of study drug (in this extension) with at least one post-baseline pharmacokinetic assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Mean (Standard Deviation) [Litre/day (L/d)]	0.210 (0.0741)

19. Secondary Outcome

Title	Pharmacokinetic (PK) of ACZ885: Volume Distribution From Serum Following Intravenous Administration (CL) in Participants
Description	The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.
Time Frame	Pre dose at Day 1, Pre dose at week 6, 12, 18, 24, 30, 36, 42, 48, follow up and at study completion (week 60)

Outcome Measure Data

Analysis Population Description

The PK set consisted of all participants who received at least one dose of study drug (in this extension) with at least one post-baseline pharmacokinetic assessment.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Mean (Standard Deviation) [Litre (L)]	3.34 (1.03)

20. Secondary Outcome

Title	Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Physical Component)
Description	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.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized participants who received at least one dose of the study drug.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	38.115 (9.9799)
Week 12	39.374 (9.7656)
Week 24	39.437 (9.2349)
Week 36	38.264 (10.0517)
Week 48	40.110 (10.3660)
End Of Study	38.295 (9.4491)

21. Secondary Outcome

Title	Health-Related Quality of Life (HRQoL) Accessed by Health Assessment Questionnaire (HAQ) Score
Description	HAQ assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3 where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question.A decrease from baseline indicates improvement for HAQ-DI. The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 to 3, with higher scores indicating greater disability.
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized participants who received at least one dose of the study drug.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	1.107 (0.6957)
Day 1	1.039 (0.7271)
Week 6	0.981 (0.6990)
Week 12	1.044 (0.6924)
Week 18	1.061 (0.7182)
Week 24	0.997 (0.7224)
Week 30	0.993 (0.7223)
Week 36	1.008 (0.7450)
Week 42	0.814 (0.8368)
Week 48	0.837 (0.7529)
Week 54 (Follow-Up)	0.859 (0.7231)
End of Study	1.089 (0.7350)

22. Secondary Outcome

Title	Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Mental Component)
Description	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.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Time Frame	Baseline Up to End Of Study (up to week 60)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized participants who received at least one dose of the study drug.

Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Measure Participants	115
Baseline	44.947 (11.9800)
Week 12	45.867 (12.5364)
Week 24	44.701 (11.9993)
Week 36	45.175 (12.1436)
Week 48	49.993 (13.0069)
End Of Study	42.346 (11.8792)

Adverse Events

Time Frame	Adverse events were collected From Start of the Study up to EOS (Week 60)
Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
All Cause Mortality
	Canakinumab (ACZ885)
	Affected / at Risk (%)	# Events
Total	1/115 (0.9%)
Serious Adverse Events
	Canakinumab (ACZ885)
	Affected / at Risk (%)	# Events
Total	8/115 (7%)
Eye disorders
Intermediate Uveitis	1/115 (0.9%)
Hepatobiliary disorders
Cholelithiasis	1/115 (0.9%)
Infections and infestations
Lower respiratory tract infection	1/115 (0.9%)
Injury, poisoning and procedural complications
Radius Fracture	1/115 (0.9%)
Burn of internal organs	1/115 (0.9%)
Hip Fracture	1/115 (0.9%)
Musculoskeletal and connective tissue disorders
Lumbar Pain	1/115 (0.9%)
Osteoarthritis	1/115 (0.9%)
Rheumatoid Arthritis	1/115 (0.9%)
Other (Not Including Serious) Adverse Events
	Canakinumab (ACZ885)
	Affected / at Risk (%)	# Events
Total	91/115 (79.1%)
Blood and lymphatic system disorders
Anaemia	4/115 (3.5%)	4
Gastrointestinal disorders
Abdominal Pain	3/115 (2.6%)	3
Abdominal pain upper	4/115 (3.5%)	4
Nausea	5/115 (4.3%)	6
General disorders
Odema peripheral	4/115 (3.5%)	5
Infections and infestations
Bronchitis	8/115 (7%)	9
Gastroenteritis	3/115 (2.6%)	3
Respiratory tract infection viral	7/115 (6.1%)	11
Urinary tract infection	3/115 (2.6%)	4
Investigations
Blood pressure increased	3/115 (2.6%)	4
Hepatic enzyme increased	4/115 (3.5%)	5
Musculoskeletal and connective tissue disorders
Back pain	6/115 (5.2%)	6
Arthralgia	5/115 (4.3%)	6
Musculoskeletal pain	4/115 (3.5%)	5
Pain in extremity	7/115 (6.1%)	9
Rheumatoid arthritis	6/115 (5.2%)	9
Nervous system disorders
Headache	11/115 (9.6%)	13
Respiratory, thoracic and mediastinal disorders
Cough	3/115 (2.6%)	3
Skin and subcutaneous tissue disorders
Skin reaction	3/115 (2.6%)	4
Vascular disorders
Hypertension	4/115 (3.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.