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A Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND-D)

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ClinicalTrials.gov Identifier: NCT01604343
Recruitment Status : Completed
First Posted : May 23, 2012
Results First Posted : January 11, 2018
Last Update Posted : January 11, 2018
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: Placebo
Drug: Sirukumab
Enrollment 1670
Recruitment Details  
Pre-assignment Details A total of 2746 participants were screened of which 1670 participants were randomized and received at least one administration of study treatment.
Arm/Group Title Placebo Placebo to 50 mg q4w Due to EE/LE/CO Sirukumab 50 mg q4w Placebo to 100 mg q2w Due to EE/LE/CO Sirukumab 100 mg q2w
Hide Arm/Group Description Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week (W) 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. Participants who were assigned to placebo group and who met EE at Week 18 or LE at Week 40 or CO at Week 52 were re-randomized to receive subcutaneous (SC) sirukumab 50 mg dose regimen q4w up to Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. All participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. Participants who were assigned to placebo group and who met EE at Week 18 or LE at Week 40 or CO at Week 52 were re-randomized to receive subcutaneous (SC) sirukumab 100 mg dose regimen q2w up to Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. All participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Period Title: Prior to W52 Administration(Through W52)
Started 556 0 557 0 557
Participants Re-randomized at Week 18 187 [1] 0 0 0 0
Participants Re-randomized at Week 40 24 [2] 0 0 0 0
Completed 458 0 481 0 470
Not Completed 98 0 76 0 87
Reason Not Completed
Lost to Follow-up             5             0             4             0             3
Withdrawal by Subject             19             0             12             0             16
Adverse Event             25             0             41             0             42
Death             5             0             2             0             4
Lack of Efficacy             24             0             5             0             14
Physician Decision             4             0             1             0             2
Pregnancy             1             0             1             0             0
Other             15             0             10             0             6
[1]
Out of 187, 95 were re-randomized to sirukumab 50 mg and 92 were re-randomized to 100 mg group.
[2]
Out of 24, 12 were re-randomized to sirukumab 50 mg and 12 were re-randomized to 100 mg group.
Period Title: Week 52 to Week 104
Started 0 243 [1] 481 241 [2] 470
Treated 0 242 481 241 470
Completed 0 200 414 195 429
Not Completed 0 43 67 46 41
Reason Not Completed
Lost to Follow-up             0             2             4             2             1
Withdrawal by Subject             0             7             12             8             4
Adverse Event             0             12             26             21             27
Death             0             4             2             5             0
Lack of Efficacy             0             6             11             2             3
Physician Decision             0             1             0             0             2
Pregnancy             0             0             1             2             1
Other             0             11             11             6             3
[1]
Participants re-randomized at Week 18 (95), 40 (12) and 52 were included
[2]
Participants re-randomized at Week 18 (92), 40 (12) and 52 were included
Period Title: Safety Follow-up Period (Week 104-120)
Started 109 27 105 36 114
Safety Population 109 26 105 36 114
Completed 79 20 72 26 85
Not Completed 30 7 33 10 29
Reason Not Completed
Lost to Follow-up             3             1             2             1             1
Withdrawal by Subject             12             4             11             3             14
Other             15             2             20             6             14
Arm/Group Title Placebo Sirukumab 50 mg q4w Sirukumab 100 mg q2w Total
Hide Arm/Group Description Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. All participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. All participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. Total of all reporting groups
Overall Number of Baseline Participants 556 557 557 1670
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 556 participants 557 participants 557 participants 1670 participants
52.9  (11.85) 52.9  (11.8) 53  (11.31) 52.9  (11.65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 556 participants 557 participants 557 participants 1670 participants
Female
436
  78.4%
447
  80.3%
452
  81.1%
1335
  79.9%
Male
120
  21.6%
110
  19.7%
105
  18.9%
335
  20.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 556 participants 557 participants 557 participants 1670 participants
Bulgaria
5
   0.9%
7
   1.3%
6
   1.1%
18
   1.1%
Canada
4
   0.7%
4
   0.7%
3
   0.5%
11
   0.7%
Chile
23
   4.1%
21
   3.8%
24
   4.3%
68
   4.1%
Colombia
17
   3.1%
13
   2.3%
11
   2.0%
41
   2.5%
Croatia
4
   0.7%
4
   0.7%
2
   0.4%
10
   0.6%
Japan
56
  10.1%
58
  10.4%
54
   9.7%
168
  10.1%
Lithuania
32
   5.8%
31
   5.6%
35
   6.3%
98
   5.9%
Malaysia
5
   0.9%
1
   0.2%
1
   0.2%
7
   0.4%
Mexico
33
   5.9%
41
   7.4%
41
   7.4%
115
   6.9%
Poland
64
  11.5%
51
   9.2%
54
   9.7%
169
  10.1%
Republic of Korea
21
   3.8%
16
   2.9%
31
   5.6%
68
   4.1%
Romania
3
   0.5%
6
   1.1%
6
   1.1%
15
   0.9%
Russian Federation
61
  11.0%
67
  12.0%
73
  13.1%
201
  12.0%
Serbia
52
   9.4%
47
   8.4%
45
   8.1%
144
   8.6%
South Africa
40
   7.2%
34
   6.1%
26
   4.7%
100
   6.0%
Taiwan, Province of China
5
   0.9%
14
   2.5%
5
   0.9%
24
   1.4%
Ukraine
50
   9.0%
50
   9.0%
52
   9.3%
152
   9.1%
United States
81
  14.6%
92
  16.5%
88
  15.8%
261
  15.6%
1.Primary Outcome
Title Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16
Hide Description ACR 20 response is greater than or equal to (>=) 20 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and >= 20% improvement in 3 of following 5 assessments:Participant’s assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant’s global assessment of disease activity by using VAS (scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician’s global assessment of disease activity using VAS (scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant’s assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received. Here, TF= treatment failure.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to non-responders if meeting TF criteria prior to week 16 or having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
26.4 54.8 53.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 28.4
Confidence Interval (2-Sided) 95%
22.8 to 33.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 27.1
Confidence Interval (2-Sided) 95%
21.6 to 32.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52
Hide Description The van der Heijde-modified Sharpe (vdH-S) score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received. Here, EE= early escape.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy full analysis set (radiographic endpoints) had randomized participants received at least 1 (partial/complete) dose of study drug with non-missing baseline vdH-S score. It was based on imputed value by EE Rules: set scores after EE missing for placebo arm; and then missing data rules in all treatment arms using linear extrapolation method.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 550 553 551
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
3.69  (9.245) 0.50  (2.961) 0.46  (3.258)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method van der waerden ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method van der waerden ANOVA
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
Hide Description The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE was used to replace the data after EE for participants who met EE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on Scale
-0.2179  (0.53081) -0.4262  (0.57631) -0.4610  (0.56784)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) mean difference
Estimated Value -0.2260
Confidence Interval (2-Sided) 95%
-0.29 to -0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.2560
Confidence Interval (2-Sided) 95%
-0.32 to -0.20
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
Hide Description An American College of Rheumatology (ACR) 50 response is defined as >= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: Participant’s assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant’s global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician’s global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant’s assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to non-responders if meeting EE or TF criteria prior to week 24 or having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
12.4 30.2 33.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 17.8
Confidence Interval (2-Sided) 95%
13.1 to 22.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 20.8
Confidence Interval (2-Sided) 95%
16.1 to 25.6
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24
Hide Description The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to not achieving DAS28 remission if meeting EE or TF criteria prior to week 24 or having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
5.6 26.0 25.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 20.5
Confidence Interval (2-Sided) 95%
16.4 to 24.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 19.9
Confidence Interval (2-Sided) 95%
15.8 to 24.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Major Clinical Response (MCR) at Week 52
Hide Description MCR- participant achieving ACR 70 response for 6 continuous months (24 weeks) in the study period (i.e., through Week 52). An ACR 70 response is defined as >= 70% improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 70% improvement in 3 of the following 5 assessments Participant’s assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant’s global assessment of disease activity by using VAS (scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician’s global assessment of disease activity using VAS (scale ranges from 0 to 10, [0=no arthritis to 10=extremely active arthritis]), Participant’s assessment of physical function as measured by HAQ-DI (scale ranges from 0= no difficulty, to 3= inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was defined as all randomized participants. Participants were set to non-responders if meeting EE, LE or TF criteria prior to week 52 or having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
1.8 5.4 9.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
1.4 to 5.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sirukumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 7.2
Confidence Interval (2-Sided) 95%
4.6 to 9.8
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Through Week 52
Hide Description An ACR 20 response is defined as >= 20 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 20% improvement in 3 of the following 5 assessments: Participant’s assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant’s global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician’s global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant’s assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to non-responders after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 7.4 18.3 15.4
Week 4 14.2 36.3 33.8
Week 6 20.3 45.8 46.9
Week 8 25.9 47.2 51.3
Week 12 27.3 53.1 53.3
Week 18 29.3 54.4 56.9
Week 20 29.5 53.7 52.8
Week 24 27.0 53.7 56.0
Week 28 31.5 53.1 57.3
Week 32 29.5 53.3 56.7
Week 36 28.4 54.0 58.2
Week 40 28.8 53.3 53.3
Week 44 27.7 49.2 54.0
Week 48 26.8 50.1 54.8
Week 52 26.6 49.9 54.8
8.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology (ACR) 50 Response
Hide Description An ACR 50 response is defined as >= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 50% improvement in 3 of the following 5 assessments: Participant’s assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant’s global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician’s global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant’s assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was defined as all randomized participants. Participants were set to non-responders after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 1.1 3.2 2.0
Week 4 2.5 9.2 9.9
Week 6 4.1 15.6 14.0
Week 8 7.7 20.3 18.9
Week 12 10.1 24.6 28.0
Week 16 10.8 30.0 26.2
Week 18 11.7 31.2 31.2
Week 20 13.5 32.7 33.4
Week 28 15.1 31.6 33.0
Week 32 14.0 33.6 35.0
Week 36 12.2 33.4 34.5
Week 40 13.3 31.1 33.4
Week 44 14.2 31.4 33.9
Week 48 14.4 32.9 34.8
Week 52 13.8 30.3 35.5
9.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology (ACR) 70 Response Through Week 52
Hide Description An ACR 70 response is defined as >= 70 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 70% improvement in 3 of the following 5 assessments: Participant’s assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant’s global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician’s global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant’s assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was defined as all randomized participants. Participants were set to non-responders after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 0.4 0.7 0.4
Week 4 0.5 2.0 3.1
Week 6 1.6 4.7 4.5
Week 8 1.6 7.2 7.2
Week 12 3.1 10.4 10.6
Week 16 4.0 13.5 13.5
Week 18 4.3 12.6 14.7
Week 20 4.0 13.1 16.0
Week 24 3.4 14.9 16.3
Week 28 5.2 16.0 16.5
Week 32 4.7 17.4 17.2
Week 36 4.7 15.8 16.2
Week 40 5.0 16.9 17.6
Week 44 5.2 16.3 17.1
Week 48 6.8 18.5 17.8
Week 52 5.4 16.5 18.5
10.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology (ACR) 90 Response Through Week 52
Hide Description An ACR 90 response is defined as >= 90 percent (%) improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and >= 90% improvement in 3 of the following 5 assessments: Participant’s assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant’s global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician’s global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant’s assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was defined as all randomized participants. Participants were set to non-responders after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 0 0 0
Week 4 0 0.2 0.2
Week 6 0.2 0.2 0.2
Week 8 0.2 1.1 0.5
Week 12 0.5 2.2 1.8
Week 16 0.9 2.5 2.9
Week 18 1.1 2.5 2.5
Week 20 0.5 3.6 4.1
Week 24 0.5 3.4 5.2
Week 28 0.4 4.5 4.7
Week 32 1.1 4.1 5.7
Week 36 0.9 4.8 5.4
Week 40 0.7 5.4 6.1
Week 44 0.5 5.0 6.6
Week 48 0.7 4.7 6.3
Week 52 1.3 4.5 5.6
11.Secondary Outcome
Title Percentage of Participants With Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Response Through Week 52
Hide Description DAS28 based on C-Reactive Protein (CRP), a statistically derived index combining tender joints (28), swollen joints (28), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both upper right extremity and upper left extremity as well as knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. Good responders: improvement from baseline greater than (>) 1.2 with DAS28 less than or equal to (<=) 3.2; moderate responders: improvement from baseline >1.2 with DAS28 >3.2 to <=5.1 or improvement from baseline >0.6 to <=1.2 with DAS28 <=5.1; non-responders: improvement from baseline <=0.6 or improvement from baseline >0.6 and <=1.2 with DAS28 >5.1. Participants were analyzed according to randomized treatment groups they were assigned to, regardless of treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to non-responders after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 18.5 72.0 72.4
Week 4 28.1 80.1 78.3
Week 6 36.7 82.4 80.3
Week 8 38.5 81.7 81.3
Week 12 43.7 83.3 81.3
Week 16 42.6 80.4 79.5
Week 18 41.5 79.7 79.4
Week 20 41.5 73.8 72.5
Week 24 37.9 71.5 72.2
Week 28 41.2 69.7 72.2
Week 32 41.4 68.2 70.6
Week 36 39.7 67.7 69.8
Week 40 39.2 66.8 67.9
Week 44 37.6 63.2 64.6
Week 48 36.7 61.9 64.6
Week 52 35.6 62.5 64.3
12.Secondary Outcome
Title Change From Baseline in Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Through Week 52
Hide Description The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. A negative change from baseline in DAS28 (CRP) (that is, a decrease from baseline) indicates improvement from baseline. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change at Week 2 -0.319  (0.7677) -1.316  (0.7776) -1.284  (0.7605)
Change at Week 4 -0.515  (0.9287) -1.638  (0.9759) -1.627  (0.9529)
Change at Week 6 -0.707  (1.0599) -1.886  (1.0622) -1.888  (1.0340)
Change at Week 8 -0.754  (1.1013) -2.016  (1.1183) -2.031  (1.1138)
Change at Week 12 -0.881  (1.1727) -2.187  (1.1995) -2.185  (1.1950)
Change at Week 16 -0.908  (1.2834) -2.264  (1.2443) -2.282  (1.2283)
Change at Week 18 -0.895  (1.2986) -2.286  (1.2690) -2.335  (1.2314)
Change at Week 20 -0.920  (1.2973) -2.367  (1.3368) -2.380  (1.3158)
Change at Week 24 -0.912  (1.3180) -2.356  (1.3599) -2.402  (1.3048)
Change at Week 28 -0.979  (1.3752) -2.417  (1.4068) -2.440  (1.3245)
Change at Week 32 -1.010  (1.3904) -2.451  (1.4141) -2.479  (1.3304)
Change at Week 36 -1.019  (1.4020) -2.461  (1.3951) -2.497  (1.3231)
Change at Week 40 -0.985  (1.4054) -2.462  (1.4180) -2.459  (1.3901)
Change at Week 44 -0.994  (1.4117) -2.442  (1.4364) -2.477  (1.4381)
Change at Week 48 -1.026  (1.4755) -2.482  (1.4630) -2.488  (1.3783)
Change at Week 52 -0.992  (1.4431) -2.491  (1.4305) -2.476  (1.4109)
13.Secondary Outcome
Title Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission Through Week 52
Hide Description The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to not achieving DAS28 remission after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 0.5 2.5 2.7
Week 4 1.6 7.9 9.3
Week 6 3.1 10.2 12.6
Week 8 3.2 13.6 17.8
Week 12 4.3 18.3 19.6
Week 16 5.8 21.2 21.9
Week 18 6.1 22.8 23.7
Week 20 5.8 26.4 25.5
Week 28 7.7 27.5 27.1
Week 32 7.7 29.6 28.4
Week 36 8.5 29.1 28.0
Week 40 7.2 27.8 27.3
Week 44 8.5 28.2 27.5
Week 48 9.0 29.6 30.2
Week 52 8.8 30.0 29.1
14.Secondary Outcome
Title Change From Baseline in Simplified Disease Activity Index (SDAI) Score Through Week 52
Hide Description The SDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, physician's global assessments of disease activity, and CRP. The total score range is from 0 to 86 with a lower score indicating less disease activity. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change at Week 2 -4.5129  (9.68032) -9.1095  (9.64598) -7.9649  (9.58765)
Change at Week 4 -7.3134  (11.87959) -13.3976  (12.00410) -12.2156  (11.65262)
Change at Week 6 -9.5833  (13.15531) -16.1013  (12.80166) -15.4404  (12.18642)
Change at Week 8 -10.0752  (13.54599) -17.6624  (12.98109) -17.1302  (12.92830)
Change at Week 12 -11.5975  (14.53181) -19.6639  (13.67016) -19.0635  (13.63444)
Change at Week 16 -11.3507  (15.72864) -20.3221  (14.14177) -20.0652  (13.85171)
Change at Week 18 -10.6805  (16.31549) -20.1215  (14.75683) -20.4858  (13.72370)
Change at Week 20 -11.0425  (16.42770) -20.8300  (15.31245) -20.8508  (14.44400)
Change at Week 24 -11.1443  (16.37909) -20.7459  (15.48312) -21.0858  (14.57962)
Change at Week 28 -11.7828  (17.04652) -21.3535  (15.98762) -21.5524  (14.69362)
Change at Week 32 -12.0835  (17.11297) -21.8176  (16.15549) -21.8530  (14.58393)
Change at Week 36 -12.2107  (17.24703) -21.9077  (15.95251) -22.1040  (14.54871)
Change at Week 40 -11.9185  (17.32206) -21.7862  (16.12260) -21.6692  (15.33635)
Change at Week 44 -11.8730  (17.41934) -21.4843  (16.33985) -21.5514  (15.78476)
Change at Week 48 -11.9055  (17.91398) -21.7238  (16.45520) -21.7991  (15.34514)
Change at Week 52 -11.7647  (17.61074) -21.9130  (16.32611) -21.7344  (15.64620)
15.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 52
Hide Description The CDAI score is a derived score of 4 components: tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, and physician's global assessments of disease activity. The total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change at Week 2 -4.38  (9.210) -6.82  (9.350) -5.65  (9.014)
Change at Week 4 -7.09  (11.241) -11.13  (11.699) -9.88  (11.166)
Change at Week 6 -9.24  (12.407) -13.79  (12.416) -13.10  (11.599)
Change at Week 8 -9.72  (12.714) -15.37  (12.593) -14.79  (12.438)
Change at Week 12 -11.19  (13.625) -17.36  (13.223) -16.74  (13.098)
Change at Week 16 -10.86  (14.716) -18.04  (13.651) -17.75  (13.261)
Change at Week 18 -10.24  (15.245) -17.82  (14.291) -18.17  (13.204)
Change at Week 20 -10.57  (15.338) -18.53  (14.809) -18.57  (13.910)
Change at Week 24 -10.68  (15.302) -18.45  (14.936) -18.80  (14.075)
Change at Week 28 -11.27  (15.926) -19.06  (15.395) -19.27  (14.168)
Change at Week 32 -11.55  (15.950) -19.57  (15.549) -19.56  (14.095)
Change at Week 36 -11.70  (16.099) -19.66  (15.455) -19.80  (14.084)
Change at Week 40 -11.46  (16.236) -19.54  (15.640) 19.3  (14.833)
Change at Week 44 -11.41  (16.126) -19.24  (15.888) -19.26  (15.264)
Change at Week 48 -11.47  (16.594) -19.47  (15.951) -19.50  (14.871)
Change at Week 52 -11.38  (16.348) -19.67  (15.834) -19.44  (15.115)
16.Secondary Outcome
Title Percentage of Participants With Simplified Disease Activity Index Based (SDAI-based) American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
Hide Description Participant having SDAI-based ACR/EULAR remission at a visit if SDAI score is of <= 3.3. SDAI derived by combining 5 disease assessments: tender joint (28), swollen joint (28) counts, participants global assessment of disease activity using VAS (scale ranges from 0 to 10 [0 =very well to 10 = very poor]), physicians global assessment of disease activity using VAS (scale ranges from 0 to 10 [0=no arthritis to 10=extremely active arthritis]) and CRP. 28 joints evaluated for swelling and tenderness are same set of 28 joints used in DAS28 includes shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of upper right and left extremities and knee joints of lower right and left extremities. Change from baseline in SDAI score measures change in disease activity, where negative change= improvement and positive change= worsening. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to not achieving SDAI-based remission after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 0.2 0 0
Week 4 0.4 0.2 1.3
Week 6 0.4 1.6 2.3
Week 8 0.7 2.9 2.9
Week 12 1.6 4.8 5.2
Week 16 2.2 5.4 6.6
Week 18 1.6 6.3 6.8
Week 20 1.6 7.5 7.7
Week 24 2.3 8.1 9.5
Week 28 2.3 9.0 8.4
Week 32 2.9 9.7 10.2
Week 36 1.8 10.1 10.6
Week 40 2.5 11.5 11.5
Week 44 2.5 9.7 11.7
Week 48 3.8 11.3 10.4
Week 52 3.2 11.5 10.6
17.Secondary Outcome
Title Percentage of Participants With Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
Hide Description A participant was considered as having achieved the Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) remission at a visit if all of the following 4 criteria were met at that visit: Tender joint count (68 joints) less than or equal to (<=) 1; Swollen joint count (66 joints) <=1; CRP <=1 milligram per deciliter (mg/dL); Patient’s Global Assessment of Disease Activity <=1 on a 0 (very well) to 10 (very poor) VAS. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Participants were set to not achieving Boolean-based remission after meeting EE, LE or TF criteria (whichever is earliest) or if having data missing.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 0.2 0.4 0
Week 4 0.2 0.4 0.7
Week 6 0 0.9 0.9
Week 8 0.2 1.3 1.8
Week 12 1.3 2.9 3.1
Week 16 1.6 3.2 4.7
Week 18 0.7 3.6 4.7
Week 20 1.3 4.3 5.6
Week 24 0.9 4.3 7.0
Week 28 1.1 5.2 6.1
Week 32 2.3 5.0 6.5
Week 36 1.3 7.0 7.9
Week 40 0.9 5.9 7.9
Week 44 1.4 5.7 7.9
Week 48 1.8 7.0 7.0
Week 52 2.2 7.0 5.7
18.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 52
Hide Description The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Negative change reflects an improvement and a positive change reflects a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change at Week 2 -0.075  (0.3809) -0.139  (0.3744) -0.128  (0.3939)
Change at Week 4 -0.130  (0.4444) -0.244  (0.4498) -0.254  (0.4184)
Change at Week 6 -0.170  (0.4657) -0.318  (0.4989) -0.360  (0.4910)
Change at Week 8 -0.172  (0.4824) -0.362  (0.5163) -0.388  (0.5163)
Change at Week 12 -0.191  (0.5055) -0.387  (0.5512) -0.399  (0.5364)
Change at Week 16 -0.201  (0.5439) -0.409  (0.5736) -0.433  (0.5489)
Change at Week 18 -0.217  (0.5266) -0.431  (0.5744) -0.464  (0.5496)
Change at Week 20 -0.209  (0.5275) -0.429  (0.6074) -0.474  (0.5797)
Change at Week 28 -0.232  (0.5515) -0.438  (0.5837) -0.471  (0.5763)
Change at Week 32 -0.225  (0.5462) -0.441  (0.6017) -0.483  (0.5886)
Change at Week 36 -0.226  (0.5585) -0.444  (0.5961) -0.461  (0.5810)
Change at Week 40 -0.230  (0.5586) -0.447  (0.5900) -0.431  (0.5921)
Change at Week 44 -0.228  (0.5601) -0.442  (0.6182) -0.456  (0.5956)
Change at Week 48 -0.227  (0.5727) -0.447  (0.6207) -0.481  (0.6043)
Change at Week 52 -0.225  (0.5693) -0.453  (0.6127) -0.470  (0.5959)
19.Secondary Outcome
Title Area Under the Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52
Hide Description HAQ-DI has 20-question in 8 functional areas: dressing, arising, eating, walking, hygiene, reaching, gripping, and daily living activities, scored from 0=no difficulty to 3=inability to perform task in that area. Overall score computed as sum of domain score divided by number of domains answered. Total possible score range 0= least difficulty to 3= extreme difficulty. AUC of change from baseline in HAQ-DI score is AUC of change from baseline in HAQ-DI score versus time. AUC was calculated based on measurement (observed HAQ-DI score change from baseline) at scheduled visits using trapezoidal rule.Functional status was determined as cumulative measure of HAQ-DI over 1 year by using AUC of change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI means greater average improvement in physical function over time. Participants analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received.
Time Frame Week 0 Through Week 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on a Scale*Day
Week 0 Through Week 24 -28.85  (69.783) -57.99  (76.384) -61.71  (75.189)
Week 0 Through Week 52 -73.55  (170.636) -145.30  (184.630) -153.03  (180.633)
20.Secondary Outcome
Title Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 52
Hide Description HAQ-DI response was defined as change of less than -0.22 from baseline in HAQ-DI score. The HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 34.4 40.6 37.0
Week 4 38.1 49.2 52.2
Week 6 42.4 56.2 58.0
Week 8 44.1 56.2 61.0
Week 12 44.6 60.1 60.9
Week 16 45.5 60.9 61.9
Week 18 45.9 62.7 65.4
Week 20 46.2 61.4 65.4
Week 24 46.9 63.0 65.4
Week 28 47.8 64.8 63.4
Week 32 46.9 62.8 63.7
Week 36 47.3 63.9 63.7
Week 40 47.3 63.7 61.8
Week 44 47.3 62.1 63.2
Week 48 47.3 61.8 64.6
Week 52 47.1 63.4 64.5
21.Secondary Outcome
Title Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Score of Less Than or Equal to 0.5
Hide Description HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. Last Observation at or prior EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 2 7.9 12.2 11.5
Week 4 9.9 15.6 16.3
Week 6 9.5 18.3 21.2
Week 8 10.6 21.7 21.0
Week 12 12.2 22.8 23.3
Week 16 13.3 24.6 26.8
Week 18 13.7 24.6 25.9
Week 20 13.1 26.0 27.5
Week 24 13.1 25.9 27.5
Week 28 13.8 26.2 28.7
Week 32 13.7 26.0 28.7
Week 36 13.7 27.5 27.5
Week 40 13.7 27.3 26.2
Week 44 13.1 27.8 27.6
Week 48 13.8 28.2 30.0
Week 52 12.4 27.5 29.3
22.Secondary Outcome
Title Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24
Hide Description vdH-S score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy full analysis set (radiographic endpoints) had randomized participants received at least 1 (partial/complete) dose of study drug with non-missing baseline vdH-S score. It was based on imputed value by EE Rules: set scores after EE missing for placebo arm; and then missing data rules in all treatment arms using linear extrapolation method.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 550 553 551
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
1.96  (5.390) 0.35  (2.149) 0.30  (2.165)
23.Secondary Outcome
Title Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Type of Damage (Erosion or JSN) at Week 24 and 52
Hide Description vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy full analysis set (radiographic endpoints) had randomized participants received at least 1 (partial/complete) dose of study drug with non-missing baseline vdH-S score. It was based on imputed value by EE Rules: set scores after EE missing for placebo arm; and then missing data rules in all treatment arms using linear extrapolation method.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 550 553 551
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Erosion Score: Change at Week 24 1.21  (3.348) 0.10  (1.306) 0.08  (1.321)
JSN Score: Change at Week 24 0.76  (2.540) 0.24  (1.404) 0.21  (1.537)
Erosion Score: Change at Week 52 2.23  (5.903) 0.12  (1.809) 0.08  (2.005)
JSN Score: Change at Week 52 1.46  (4.311) 0.38  (1.839) 0.38  (2.184)
24.Secondary Outcome
Title Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Region Hand or Feet and Type Erosion or JSN at Week 24 and 52
Hide Description vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., erosion score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy full analysis set (radiographic endpoints) had randomized participants received at least 1 (partial/complete) dose of study drug with non-missing baseline vdH-S score. It was based on imputed value by EE Rules: set scores after EE missing for placebo arm; and then missing data rules in all treatment arms using linear extrapolation method.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 550 553 551
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change in Hand Erosion Score at Week 24 0.74  (2.406) 0.07  (0.920) 0.03  (0.966)
Change in Hand JSN Score at Week 24 0.51  (1.818) 0.16  (1.025) 0.16  (1.021)
Change in Foot Erosion Score at Week 24 0.46  (1.459) 0.03  (0.682) 0.05  (0.754)
Change in Foot JSN Score at Week 24 0.25  (1.207) 0.09  (0.722) 0.06  (1.152)
Change in Hand Erosion Score at Week 52 1.43  (4.378) 0.09  (1.296) 0.03  (1.312)
Change in Hand JSN Score at Week 52 0.98  (3.196) 0.25  (1.378) 0.28  (1.808)
Change in Foot Erosion Score at Week 52 0.80  (2.460) 0.03  (0.955) 0.06  (1.302)
Change in Foot JSN Score at Week 52 0.48  (2.013) 0.13  (0.929) 0.10  (1.171)
25.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) Greater Than Smallest Detectable Change (SDC) at Weeks 24 and 52
Hide Description vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S). JE is summary of erosion severity in 32 of hand and 12 of feet joints, scored according to the surface area, from 0 (no erosion) to 5 (complete collapse of bone) whereas the JSN is summary of severity of 30 of hand and 12 of feet joints, scored according to the subluxation from 0 (normal) to 4 (bony ankylosis or complete luxation). The SDC is smallest change in score that is considered to be assessed correctly based on limits of agreement (that is., above the measurement error). The SDC for change from baseline in vdH-S Score is determined as: SDC=1.96 * SD / (root 2 * root k), where SD is the standard deviation of the difference between 2 readers in change from baseline in vdH-S score; k is the number of readers. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Weeks 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy full analysis set (radiographic endpoints) had randomized participants received at least 1 (partial/complete) dose of study drug with non-missing baseline vdH-S score. It was based on imputed value by EE Rules: set scores after EE missing for placebo arm; and then missing data rules in all treatment arms using linear extrapolation method.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 550 553 551
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 24 25.3 8.3 7.6
Week 52 35.5 12.1 12.0
26.Secondary Outcome
Title Percentage of Participants With a Change of Less Than or Equal to 0 From Baseline in Van Der Heijde Modified Sharpe (vdH-S) Score at Weeks 24 and 52
Hide Description vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS of (i.e., erosion score + JSN score) 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy full analysis set (radiographic endpoints) had randomized participants received at least 1 (partial/complete) dose of study drug with non-missing baseline vdH-S score. It was based on imputed value by EE Rules: set scores after EE missing for placebo arm; and then missing data rules in all treatment arms using linear extrapolation method.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 550 553 551
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 24 48.4 65.8 68.8
Week 52 45.5 59.0 62.4
27.Secondary Outcome
Title Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) by Reader at Weeks 24 and 52
Hide Description vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32*5) and MAX JES for F- 120 (12*10 [5*2 sides of foot]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30*4), and MAX JSS for F-48(12*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Weeks 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy full analysis set (radiographic endpoints) had randomized participants received at least 1 (partial/complete) dose of study drug with non-missing baseline vdH-S score. It was based on imputed value by EE Rules: set scores after EE missing for placebo arm; and then missing data rules in all treatment arms using linear extrapolation method.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 550 553 551
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Reader 1 at Week 24 Number Analyzed 550 participants 551 participants 550 participants
2.06  (5.616) 0.21  (2.495) 0.20  (2.773)
Reader 2 at Week 24 Number Analyzed 550 participants 553 participants 551 participants
1.65  (5.053) 0.38  (1.969) 0.33  (1.830)
Reader 1 at Week 52 Number Analyzed 447 participants 459 participants 467 participants
2.99  (7.940) 0.54  (3.285) 0.29  (3.325)
Reader 2 at Week 52 Number Analyzed 447 participants 460 participants 467 participants
2.65  (7.331) 0.54  (2.660) 0.35  (2.184)
28.Secondary Outcome
Title Change From Baseline in Serum C-reactive Protein (CRP) Levels Through Week 52
Hide Description Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. The last observation at or prior to EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Milligram per Deciliter
Baseline 2.5148  (3.38577) 2.4145  (2.62179) 2.3952  (2.64241)
Change at Week 2 -0.1339  (2.86946) -2.2867  (2.44604) -2.3198  (2.64772)
Change at Week 4 -0.2209  (2.94279) -2.2707  (2.41525) -2.3406  (2.64584)
Change at Week 6 -0.3432  (2.96865) -2.3124  (2.44604) -2.3451  (2.64678)
Change at Week 8 -0.3561  (3.05281) -2.2919  (2.41368) -2.3392  (2.65864)
Change at Week 12 -0.4099  (3.22085) -2.3038  (2.43828) -2.3274  (2.67383)
Change at Week 16 -0.4890  (3.17554) -2.2841  (2.43707) -2.3166  (2.65115)
Change at Week 18 -0.4375  (3.48359) -2.3030  (2.45255) -2.3114  (2.65919)
Change at Week 20 -0.4682  (3.21483) -2.2973  (2.44855) -2.2798  (2.74939)
Change at Week 24 -0.4610  (3.31445) -2.2974  (2.45343) -2.2891  (2.73480)
Change at Week 28 -0.5108  (3.34288) -2.2937  (2.45419) -2.2820  (2.73435)
Change at Week 32 -0.5332  (3.39542) -2.2474  (2.63824) -2.2907  (2.73375)
Change at Week 36 -0.5128  (3.36374) -2.2515  (2.62647) -2.3085  (2.73396)
Change at Week 40 -0.4623  (3.46179) -2.2429  (2.64450) -2.3032  (2.73402)
Change at Week 44 -0.4631  (4.00446) -2.2398  (2.65898) -2.2895  (2.75035)
Change at Week 48 -0.4372  (4.15311) -2.2561  (2.62491) -2.2944  (2.75776)
Change at Week 52 -0.3854  (3.96633) -2.2399  (2.64267) -2.2976  (2.73878)
29.Secondary Outcome
Title Change From Baseline in the Duration of Morning Stiffness Through Week 52
Hide Description Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (If none was present = 0; If morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported; If stiffness persisted the entire day, 1440 minutes was recorded). Negative values for this outcome measure represent improvement, i.e. shortening of duration of morning stiffness. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was defined as all randomized participants. Here 'N'(number of participants analyzed): Evaluable for this outcome measure. Last Observation Carried Forward (LOCF) method was used to impute missing values. The last observation at or prior to EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 552 552 555
Mean (Standard Deviation)
Unit of Measure: Minutes
Change at Week 2 -22.5  (184.96) -35.2  (212.94) -24.0  (177.41)
Change at Week 4 -27.2  (202.02) -61.6  (213.09) -45.1  (181.13)
Change at Week 6 -35.3  (190.54) -81.0  (207.07) -70.3  (206.41)
Change at Week 8 -41.7  (171.05) -84.1  (232.34) -79.6  (213.42)
Change at Week 12 -53.2  (179.24) -88.1  (220.03) -89.4  (217.48)
Change at Week 16 -52.2  (173.24) -82.2  (241.75) -84.1  (224.72)
Change at Week 18 -60.2  (191.68) -84.6  (239.43) -88.5  (223.95)
Change at Week 20 -62.0  (193.64) -93.5  (234.10) -90.0  (229.08)
Change at Week 24 -63.7  (195.58) -96.7  (228.31) -95.5  (234.19)
Change at Week 28 -68.3  (195.42) -95.2  (230.36) -98.0  (235.03)
Change at Week 32 -68.9  (196.31) -96.5  (230.46) -96.5  (231.25)
Change at Week 36 -68.8  (196.90) -96.5  (228.71) -95.2  (226.37)
Change at Week 40 -68.7  (197.06) -95.7  (243.78) -95.9  (233.28)
Change at Week 44 -69.9  (197.38) -96.6  (232.42) -97.0  (234.63)
Change at Week 48 -69.6  (195.50) -97.8  (238.36) -97.0  (230.66)
Change at Week 52 -67.3  (196.98) -99.1  (233.82) -97.7  (231.53)
30.Secondary Outcome
Title Change From Baseline in Physical and Mental Component Summary Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 24 and 52
Hide Description SF-36 questionnaire is health related quality of life (QOL) instrument with 36 questions with 8 multi-item scales (evaluated limitations in): physical functioning due to health problems; usual role activities due to physical health problems; Bodily pain; General mental health (psychological distress and well-being); usual role activities due to personal or emotional problems; social functioning due to physical or mental health problems; Vitality (energy and fatigue); General health perception. Each 8 scales scored from 0 to 100 with higher scores= better health. Based on scale scores, summary scores, physical component score (PCS) and mental component score (MCS) will be derived. Scoring is derived based on algorithm developed in software provided by developer. Summary MCS and PCS score is also scaled from 0 to 100 with higher scores= better health. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments they actually received.
Time Frame Baseline, Week 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. The last observation at or prior to EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
PCS :Change at Week 24 2.290  (6.2790) 5.358  (7.3312) 5.850  (7.0677)
PCS :Change at Week 52 2.423  (6.8069) 5.661  (7.7405) 6.162  (7.2277)
MCS :Change at Week 24 2.892  (9.1766) 4.898  (9.6508) 4.216  (9.4819)
MCS :Change at Week 52 2.690  (9.5698) 5.351  (9.6397) 4.767  (9.7991)
31.Secondary Outcome
Title Percentage of Participants With Greater Than or Equal to 4-Point Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 8, 16, 24, 36 and 52
Hide Description The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The questionnaire consists of 13 questions that assess a participant’s level of fatigue and tiredness over the last 7 days. Each question is graded on a 5-point scale (0 - 4); and accordingly, the total FACIT-Fatigue scores can range from 0 to 52, with lower score reflecting more fatigue and higher scores reflecting less fatigue. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Week 8, 16, 24, 36 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. The last observation at or prior to EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 8 41.0 55.8 54.9
Week 16 42.4 58.0 58.9
Week 24 43.9 61.4 59.4
Week 36 39.7 57.8 56.2
Week 52 41.0 59.1 60.5
32.Secondary Outcome
Title Change From Baseline in Total Scores of Work Limitations Questionnaire (WLQ) Week 8, 16, 24, 36 and 52
Hide Description The Work Limitations Questionnaire (WLQ) was used to measure the impairment in work-related productivity, with reference to the previous two weeks. Each work-related question is scored from 0 to 4 and the total score ranges from 0-100, with lower scores signifying fewer limitations at work. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 8, 16, 24, 36 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was defined as all randomized participants. Here 'N'(number of participants analyzed): Evaluable for this outcome measure. Last Observation Carried Forward (LOCF) method was used to impute missing values. The last observation at or prior to EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 227 223 223
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 8 -0.812  (3.6230) -1.946  (3.8040) -2.202  (3.8437)
Week 16 -0.840  (4.6414) -2.406  (4.1403) -2.600  (4.3066)
Week 24 -1.019  (4.5328) -2.765  (4.4381) -2.884  (4.5873)
Week 36 -0.940  (4.7982) -2.921  (4.4205) -2.952  (4.5640)
Week 52 -0.732  (5.0288) -3.057  (4.5290) -2.936  (4.3940)
33.Secondary Outcome
Title Change From Baseline in EuroQol Health State Visual Analogue Scale (EQ VAS)
Hide Description The EuroQol Health State Visual Analogue Scale (EQ VAS) records the respondent’s self-rated health on a vertical line, VAS where the endpoints are labeled as 0= ‘Worst imaginable health state’ and 100= ‘Best imaginable health state’. The EQ VAS can be used as a quantitative measure of health outcome as judged by the individual respondents. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame Baseline, Week 8, 16, 24, 36 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was defined as all randomized participants. Here 'N'(number of participants analyzed): Evaluable for this outcome measure. Last Observation Carried Forward (LOCF) method was used to impute missing values. The last observation at or prior to EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 554 557 556
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change at Week 8 5.61  (24.415) 11.64  (26.979) 12.24  (26.025)
Change at Week 16 5.83  (26.177) 14.09  (28.581) 14.36  (27.884)
Change at Week 24 6.71  (26.520) 14.86  (28.747) 16.41  (28.830)
Change at Week 52 8.30  (26.144) 16.80  (28.595) 17.14  (28.329)
34.Secondary Outcome
Title Change From Baseline in EuroQol EQ-5D-3L Descriptive System
Hide Description The EQ-5D-3L Descriptive System comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time Frame at Week 8, 16, 24, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Last Observation Carried Forward (LOCF) method was used to impute missing values. The last observation at or prior to EE/LE was used to replace the data after EE/LE for participants who met EE/LE criteria.
Arm/Group Title Placebo Sirukumab 50 mg Sirukumab 100 mg
Hide Arm/Group Description:
Participants received Placebo subcutaneously (SC) every 2 weeks (q2w) from Week 0 up to Week 50. Participants who met early escape (EE) criteria at Week 18, or late escape (LE) at Week 40, or cross-over (CO) at Week 52 were rerandomized to receive sirukumab 50 or 100 mg through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
Participants received 50 mg of sirukumab subcutaneously every 4 weeks (q4w) for 104 weeks and in between placebo SC injections was received at Weeks 2, 6, and q4w through Week 104.
Participants received 100 mg of sirukumab SC injections at Weeks 0, 2, and q2w through Week 104.
Overall Number of Participants Analyzed 556 557 557
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change at Week 8 0.1041  (0.31794) 0.1734  (0.32473) 0.1647  (0.30146)
Change at Week 16 0.1131  (0.33788) 0.1831  (0.34875) 0.1899  (0.31149)
Change at Week 24 0.1263  (0.33539) 0.1885  (0.33867) 0.2057  (0.32081)
Change at Week 52 0.1255  (0.34312) 0.1950  (0.33448) 0.2007  (0.32895)
Time Frame Screening up to Week 120
Adverse Event Reporting Description Safety population included all participants received at least 1 partial or complete dose of study drug and analyzed in the treatment they actually received over study period, regardless of the treatments they were randomized to. One Participant randomized to sirukumab 50 mg but inadvertently received 1 dose of 100 mg at week 16. The participant was included in 100 mg group for safety, due to which total participants increased by 1 in 100 mg group (558) and decreased by 1 in 50 mg group (556).
 
Arm/Group Title Week 0 to Week 120-Placebo W0 to W120-Placebo to Sirukumab 50 mg q4w Due to EE/LE or CO W0 to W120- Sirukumab 50 mg q4w W0 to W120- Placebo to Sirukumab 100 mg q2w Due to EE/LE or CO W0 to W120-Sirukumab 100 mg q2w
Hide Arm/Group Description Participants received matching placebo from week 0 to week 50, every 2 weeks (q2w) until either early escape (EE) at Week 18 or late escape (LE) at Week 40 or crossover (CO) at Week 52 and were rerandomized to subcutaneous (SC) sirukumab 50 mg q4w or sirukumab 100 mg q2w dose regimens up to Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. Participants who received placebo in the placebo controlled period were rerandomized (due to EE at Week 18 or LE at Week 40 or CO at Week 52) to receive subcutaneous (SC) sirukumab 50 mg q4w dose regimen up to Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. Participants received 50 mg of sirukumab SC injections at Weeks 0, 4, and q4w through Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. Participants who received placebo in the placebo controlled period were rerandomized (due to EE at Week 18 or LE at Week 40 or CO at Week 52) to receive subcutaneous (SC) sirukumab 100 mg q2w dose up to Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120. Participants received 100 mg of sirukumab SC injections at Weeks 0, 2 and q2w throught Week 104. Participants who completed study agent administration up to Week 104 and did not elect for long term extension (LTE) were followed up for safety from Week 104 up to Week 120.
All-Cause Mortality
Week 0 to Week 120-Placebo W0 to W120-Placebo to Sirukumab 50 mg q4w Due to EE/LE or CO W0 to W120- Sirukumab 50 mg q4w W0 to W120- Placebo to Sirukumab 100 mg q2w Due to EE/LE or CO W0 to W120-Sirukumab 100 mg q2w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Week 0 to Week 120-Placebo W0 to W120-Placebo to Sirukumab 50 mg q4w Due to EE/LE or CO W0 to W120- Sirukumab 50 mg q4w W0 to W120- Placebo to Sirukumab 100 mg q2w Due to EE/LE or CO W0 to W120-Sirukumab 100 mg q2w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   40/556 (7.19%)   30/242 (12.40%)   111/556 (19.96%)   35/241 (14.52%)   97/558 (17.38%) 
Blood and lymphatic system disorders           
Anaemia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  2/558 (0.36%) 
Neutropenia * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Pancytopenia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Thrombocytopenia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  2/558 (0.36%) 
Cardiac disorders           
Acute Left Ventricular Failure * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Angina Pectoris * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Atrial Fibrillation * 1  1/556 (0.18%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Bradycardia * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Cardiac Failure Congestive * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Cardiopulmonary Failure * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Myocardial Infarction * 1  0/556 (0.00%)  1/242 (0.41%)  3/556 (0.54%)  1/241 (0.41%)  1/558 (0.18%) 
Sinus Bradycardia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Endocrine disorders           
Basedow's Disease * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Goitre * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Eye disorders           
Amaurosis Fugax * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Cataract * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  1/558 (0.18%) 
Keratitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Retinal Detachment * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Scleritis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Ulcerative Keratitis * 1  0/556 (0.00%)  0/242 (0.00%)  2/556 (0.36%)  0/241 (0.00%)  0/558 (0.00%) 
Gastrointestinal disorders           
Abdominal Strangulated Hernia * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Colitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Diarrhoea * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Diverticular Perforation * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Enterocele * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Erosive Duodenitis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Gastric Perforation * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Gastric Polyps * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Gastric Ulcer * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Gastric Ulcer Haemorrhage * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Gastritis Erosive * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Gastrointestinal Hypomotility * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Gastrointestinal Necrosis * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Gastrointestinal Perforation * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Haemorrhoidal Haemorrhage * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Incarcerated Inguinal Hernia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Intestinal Obstruction * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Pancreatic Fistula * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Pancreatitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Retroperitoneal Haemorrhage * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Vomiting * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
General disorders           
Asthenia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Chest Pain * 1  0/556 (0.00%)  1/242 (0.41%)  1/556 (0.18%)  0/241 (0.00%)  2/558 (0.36%) 
Death * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  1/241 (0.41%)  0/558 (0.00%) 
Influenza Like Illness * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Medical Device Site Joint Inflammation * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Serositis * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Sudden Cardiac Death * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Hepatobiliary disorders           
Cholecystitis * 1  0/556 (0.00%)  0/242 (0.00%)  2/556 (0.36%)  1/241 (0.41%)  3/558 (0.54%) 
Cholecystitis Acute * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Cholelithiasis * 1  0/556 (0.00%)  0/242 (0.00%)  2/556 (0.36%)  1/241 (0.41%)  3/558 (0.54%) 
Gallbladder Perforation * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Hepatic Cyst * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Hepatic Steatosis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Jaundice Cholestatic * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Non-Alcoholic Steatohepatitis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Immune system disorders           
Drug Hypersensitivity * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Infections and infestations           
Abdominal Abscess * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Abdominal Sepsis * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Abscess * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Abscess Limb * 1  0/556 (0.00%)  0/242 (0.00%)  3/556 (0.54%)  0/241 (0.00%)  4/558 (0.72%) 
Abscess Soft Tissue * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Appendicitis * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  2/558 (0.36%) 
Appendicitis Perforated * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Arthritis Bacterial * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Bacterial Food Poisoning * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Bacterial Sepsis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Bronchitis * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Cellulitis * 1  1/556 (0.18%)  0/242 (0.00%)  7/556 (1.26%)  2/241 (0.83%)  5/558 (0.90%) 
Cellulitis Staphylococcal * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Cytomegalovirus Colitis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Dengue Fever * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  1/241 (0.41%)  0/558 (0.00%) 
Device Related Infection * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Diverticulitis * 1  0/556 (0.00%)  1/242 (0.41%)  4/556 (0.72%)  0/241 (0.00%)  0/558 (0.00%) 
Endophthalmitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Epididymitis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Erysipelas * 1  0/556 (0.00%)  0/242 (0.00%)  2/556 (0.36%)  0/241 (0.00%)  1/558 (0.18%) 
Escherichia Bacteraemia * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Extradural Abscess * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Eye Infection Fungal * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Gangrene * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Gastroenteritis * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Hepatitis E * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Herpes Zoster * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Infected Bite * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Infectious Pleural Effusion * 1  1/556 (0.18%)  1/242 (0.41%)  2/556 (0.36%)  0/241 (0.00%)  0/558 (0.00%) 
Infective Spondylitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Intervertebral Discitis * 1  0/556 (0.00%)  1/242 (0.41%)  1/556 (0.18%)  1/241 (0.41%)  1/558 (0.18%) 
Localised Infection * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Lung Abscess * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Lymphangitis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Meningitis * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Necrotising Fasciitis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Osteomyelitis * 1  0/556 (0.00%)  0/242 (0.00%)  2/556 (0.36%)  0/241 (0.00%)  2/558 (0.36%) 
Osteomyelitis Chronic * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Perirectal Abscess * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Peritonitis * 1  1/556 (0.18%)  2/242 (0.83%)  3/556 (0.54%)  0/241 (0.00%)  0/558 (0.00%) 
Peritonsillar Abscess * 1  0/556 (0.00%)  0/242 (0.00%)  2/556 (0.36%)  0/241 (0.00%)  1/558 (0.18%) 
Pharyngitis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Pneumonia * 1  0/556 (0.00%)  1/242 (0.41%)  11/556 (1.98%)  1/241 (0.41%)  10/558 (1.79%) 
Pneumonia Bacterial * 1  1/556 (0.18%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Pneumonia Necrotising * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Post Procedural Infection * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Postoperative Wound Infection * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  1/558 (0.18%) 
Pulmonary Tuberculosis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Pyelonephritis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Pyelonephritis Acute * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Pyoderma * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Pyonephrosis * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Salpingitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  1/558 (0.18%) 
Salpingo-Oophoritis * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Sepsis * 1  1/556 (0.18%)  2/242 (0.83%)  3/556 (0.54%)  1/241 (0.41%)  5/558 (0.90%) 
Septic Shock * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  1/558 (0.18%) 
Skin Infection * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Soft Tissue Infection * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Subcutaneous Abscess * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Urinary Tract Infection * 1  0/556 (0.00%)  1/242 (0.41%)  1/556 (0.18%)  1/241 (0.41%)  3/558 (0.54%) 
Varicella * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Wound Infection * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Injury, poisoning and procedural complications           
Abdominal Injury * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Chemical Peritonitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Concussion * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Contusion * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Epiphyseal Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Facial Bones Fracture * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Femoral Neck Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Femur Fracture * 1  1/556 (0.18%)  1/242 (0.41%)  2/556 (0.36%)  1/241 (0.41%)  0/558 (0.00%) 
Foot Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Hand Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Hip Fracture * 1  1/556 (0.18%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Humerus Fracture * 1  1/556 (0.18%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Joint Capsule Rupture * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Joint Dislocation * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Kidney Rupture * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Laceration * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Ligament Sprain * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Lower Limb Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Lumbar Vertebral Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Meniscus Injury * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Multiple Fractures * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Muscle Rupture * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Post Procedural Complication * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Postoperative Wound Complication * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Procedural Haemorrhage * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Procedural Pain * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Radius Fracture * 1  0/556 (0.00%)  1/242 (0.41%)  1/556 (0.18%)  0/241 (0.00%)  5/558 (0.90%) 
Rib Fracture * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Road Traffic Accident * 1  0/556 (0.00%)  2/242 (0.83%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Spinal Compression Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Tendon Injury * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Tendon Rupture * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  1/241 (0.41%)  1/558 (0.18%) 
Ulna Fracture * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Upper Limb Fracture * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Wound Dehiscence * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Investigations           
Alanine Aminotransferase Increased * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  3/558 (0.54%) 
Aspartate Aminotransferase Increased * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  2/241 (0.83%)  0/558 (0.00%) 
Blood Bilirubin Increased * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  2/241 (0.83%)  0/558 (0.00%) 
Chest X-Ray Abnormal * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Hepatic Enzyme Increased * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Liver Function Test Increased * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  1/558 (0.18%) 
Weight Decreased * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Metabolism and nutrition disorders           
Dehydration * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Diabetes Mellitus * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Hypercalcaemia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Hyperglycaemia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Hypokalaemia * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Atlantoaxial Instability * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Back Pain * 1  0/556 (0.00%)  1/242 (0.41%)  1/556 (0.18%)  0/241 (0.00%)  1/558 (0.18%) 
Bursitis * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Chondromalacia * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Fistula * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Fistula Discharge * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Foot Deformity * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  2/558 (0.36%) 
Intervertebral Disc Disorder * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Intervertebral Disc Protrusion * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Lumbar Spinal Stenosis * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Musculoskeletal Chest Pain * 1  0/556 (0.00%)  1/242 (0.41%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Osteoarthritis * 1  1/556 (0.18%)  1/242 (0.41%)  4/556 (0.72%)  1/241 (0.41%)  2/558 (0.36%) 
Rheumatoid Arthritis * 1  6/556 (1.08%)  0/242 (0.00%)  5/556 (0.90%)  1/241 (0.41%)  5/558 (0.90%) 
Rheumatoid Nodule * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Rotator Cuff Syndrome * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Spinal Pain * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Spondylolisthesis * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Synovitis * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  1/241 (0.41%)  0/558 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Acute Myeloid Leukaemia * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Adrenal Adenoma * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Basal Cell Carcinoma * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)  0/241 (0.00%)  0/558 (0.00%) 
Benign Neoplasm of Thyroid Gland * 1  1/556 (0.18%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  0/558 (0.00%) 
Bladder Cancer * 1  0/556 (0.00%)  0/242 (0.00%)  0/556 (0.00%)  0/241 (0.00%)  1/558 (0.18%) 
Bladder Transitional Cell Carcinoma * 1  0/556 (0.00%)  0/242 (0.00%)  1/556 (0.18%)