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An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01791153
Recruitment Status : Completed
First Posted : February 13, 2013
Results First Posted : May 18, 2017
Last Update Posted : June 18, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Giant Cell Arteritis
Interventions Drug: Tocilizumab
Drug: Prednisone
Drug: Tocilizumab Placebo
Drug: Prednisone Placebo
Drug: Corticosteroids
Drug: Methotrexate
Enrollment 251
Recruitment Details The study consists of 2 parts: a 52-week double-blind treatment period (Part 1) followed by a 104-week open label long-term follow-up period (Part 2).
Pre-assignment Details Of the 363 participants screened, a total of 251 participants were randomized into the study. One participant who was randomized to the "Tocilizumab q2w + 26 weeks prednisone taper" group withdrew on the same day of randomization and did not receive any study treatment. This participant was not included in any of the study analyses.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper Part 2: No Tocilizumab (Placebo in Part 1) Part 2: No Tocilizumab (Tocilizumab in Part 1) Part 2: Tocilizumab (Placebo in Part 1) Part 2: Tocilizumab (Tocilizumab in Part 1)
Hide Arm/Group Description Participants received tocilizumab at a dose of 162 milligrams (mg) as subcutaneous (SC) injection every week (qw) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab at a dose of 162 mg as SC injection every 2 weeks (q2w) (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks. Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received placebo during Part 1 (Weeks 1 to 52). Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received tocilizumab during Part 1 (Weeks 1 to 52). Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received placebo during Part 1 (Weeks 1 to 52). Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received tocilizumab during Part 1 (Weeks 1 to 52).
Period Title: Part 1: Blinded Period
Started 100 49 50 51 0 0 0 0
Completed 85 [1] 41 [1] 44 [1] 46 [1] 0 0 0 0
Not Completed 15 8 6 5 0 0 0 0
Reason Not Completed
Adverse Event             7             3             2             0             0             0             0             0
Lack of Efficacy             1             3             2             2             0             0             0             0
Non-Compliance             1             0             0             0             0             0             0             0
Physician Decision             0             0             0             1             0             0             0             0
Protocol Violation             0             0             0             1             0             0             0             0
Withdrawal by Subject             6             2             2             1             0             0             0             0
[1]
Completed Study to Week 52
Period Title: Part 2: Open-label Period
Started 0 0 0 0 40 58 50 67
Completed 0 0 0 0 38 54 44 61
Not Completed 0 0 0 0 2 4 6 6
Reason Not Completed
Adverse Event             0             0             0             0             0             1             1             2
Death             0             0             0             0             0             1             1             1
Lost to Follow-up             0             0             0             0             0             0             1             0
Lack of Efficacy             0             0             0             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             1             1             3             2
Physician Decision             0             0             0             0             1             1             0             0
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper Total
Hide Arm/Group Description Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 100 49 50 51 250
Hide Baseline Analysis Population Description
Safety Population included all participants who received at least one administration of study drug and provided at least one post-dose safety assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 49 participants 50 participants 51 participants 250 participants
69.5  (8.50) 69.4  (8.29) 69.3  (8.14) 67.8  (7.70) 69.1  (8.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 49 participants 50 participants 51 participants 250 participants
Female
78
  78.0%
34
  69.4%
38
  76.0%
37
  72.5%
187
  74.8%
Male
22
  22.0%
15
  30.6%
12
  24.0%
14
  27.5%
63
  25.2%
1.Primary Outcome
Title Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper)
Hide Description Remission was defined as the absence of flare and normalization of the C-reactive protein (CRP) (less than [<] 1 milligram per deciliter [mg/dL]). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) attributable to GCA. A single CRP elevation (>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (>/=1 mg/dL) at the next study visit.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants randomized into the study who received at least one administration of study drug.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Overall Number of Participants Analyzed 100 49 50
Measure Type: Number
Unit of Measure: percentage of participants
56.0 53.1 14.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (less than or equal to [</=] 30 mg/day, greater than [>] 30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 42.00
Confidence Interval (2-Sided) 99.5%
18.00 to 66.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 39.06
Confidence Interval (2-Sided) 99.5%
12.46 to 65.66
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper)
Hide Description Remission was defined as the absence of flare and normalization of the CRP (<1 mg/dL). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR >/=30 mm/hr attributable to GCA. A single CRP elevation (>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (>/=1 mg/dL) at the next study visit.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 51
Measure Type: Number
Unit of Measure: percentage of participants
56.0 53.1 17.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Non-Inferiority or Equivalence
Comments The tocilizumab group was to be considered as non-inferior to the placebo group if the lower limit of the two-sided 99.5% confidence interval was >/= -22.5%.
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 38.35
Confidence Interval (2-Sided) 99.5%
17.89 to 58.81
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cochran-Mantel-Haenszel model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Non-Inferiority or Equivalence
Comments The tocilizumab group was to be considered as non-inferior to the placebo group if the lower limit of the two-sided 99.5% confidence interval was >/= -22.5%.
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 35.41
Confidence Interval (2-Sided) 99.5%
10.41 to 60.41
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to First GCA Disease Flare
Hide Description Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR >/=30 mm/hr attributable to GCA. Participants who withdrew from the study prior to Week 52 were censored from the time of withdrawal.
Time Frame Up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 50 51
Median (99% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
165.0
(120.0 to 260.0)
295.0 [1] 
(168.0 to NA)
[1]
Data could not be calculated due to low number of participants who had an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.23
Confidence Interval (2-Sided) 99%
0.11 to 0.46
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 99%
0.18 to 0.82
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.28
Confidence Interval (2-Sided) 99%
0.12 to 0.66
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Cox proportional hazards model adjusted for the stratification factor of starting prednisone dose (</=30 mg/day, >30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0316
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 99%
0.20 to 1.16
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Total Cumulative Prednisone Dose
Hide Description The median total cumulative prednisone dose over the 52 weeks for each treatment group and the corresponding 95% confidence intervals are presented.
Time Frame Up to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 50 51
Median (95% Confidence Interval)
Unit of Measure: milligrams (mg)
1862.00
(1582.0 to 1942.0)
1862.00
(1568.0 to 2239.5)
3296.00
(2729.5 to 4023.5)
3817.50
(2817.5 to 4425.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (<=30 mg/day, > 30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (<=30 mg/day, > 30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (<=30mg/day, >30mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Van Elteren's test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments The treatment groups were compared using a Van Elteren's test stratified by starting prednisone dose (<=30 mg/day, > 30 mg/day).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren's test
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52
Hide Description The SF-36 is a standardized questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical Component Score (PCS) and Mental Component Score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). A positive change from baseline indicates improvement. No imputation was used for missing data. Data was set to missing for participants who received escape therapy.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 97 49 48 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
PCS: Baseline (n=97,49,48,49) 43.10  (9.43) 40.62  (8.00) 42.65  (10.87) 41.12  (9.97)
PCS: Change at Week 52 (n=59,26,9,18) 5.37  (7.38) 2.71  (8.86) 2.08  (12.11) -2.80  (6.98)
MCS: Baseline (n=97,49,48,49) 42.77  (12.43) 47.67  (12.59) 42.73  (12.13) 40.45  (13.73)
MCS: Change at Week 52 (n=59,26,9,18) 8.21  (10.35) 1.98  (7.17) 4.99  (7.54) 2.60  (10.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8067
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value 0.61
Confidence Interval (2-Sided) 99%
-5.86 to 7.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0252
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value 4.44
Confidence Interval (2-Sided) 99%
-0.69 to 9.56
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8374
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -0.56
Confidence Interval (2-Sided) 99%
-7.64 to 6.53
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments MCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1468
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value 3.27
Confidence Interval (2-Sided) 99%
-2.59 to 9.14
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0570
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value 4.38
Confidence Interval (2-Sided) 99%
-1.58 to 10.34
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value 5.59
Confidence Interval (2-Sided) 99%
0.86 to 10.32
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2218
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value 3.04
Confidence Interval (2-Sided) 99%
-3.43 to 9.51
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments PCS: Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0412
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value 4.25
Confidence Interval (2-Sided) 99%
-1.14 to 9.64
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52
Hide Description Participants assessed their current disease activity on a 0-100 millimeter (mm) VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity. A negative change from baseline indicates improvement.
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 49 51
Mean (Standard Deviation)
Unit of Measure: mm
Baseline (n=100,49,49,51) 43.61  (25.66) 46.65  (25.60) 35.73  (28.15) 47.78  (27.80)
Change at Week 52 (n=60,26,11,18) -19.68  (33.64) -22.69  (22.41) -8.45  (24.81) -10.00  (35.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0312
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -15.6
Confidence Interval (2-Sided) 99%
-34.3 to 3.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0476
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -11.8
Confidence Interval (2-Sided) 99%
-27.2 to 3.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 26 Weeks Prednisone Taper
Comments Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0059
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -21.9
Confidence Interval (2-Sided) 99%
-42.4 to -1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper, Part 1: Placebo + 52 Weeks Prednisone Taper
Comments Change at Week 52: Repeated measures model used for analysis included the following covariates and interactions: treatment, starting prednisone dose (<=30mg/day, >30mg/day), visit, treatment-by-visit interaction, starting dose-by-visit interaction, baseline score and baseline score-by-visit interaction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0081
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Means
Estimated Value -18.2
Confidence Interval (2-Sided) 99%
-35.8 to -0.5
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab
Hide Description AUCtau is the model-predicted area under the tocilizumab serum concentration versus time curve from time zero to the end of dosing interval. AUCtau is measured in microgram*day per milliliter (mcg*day/mL).
Time Frame Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics (PK)-evaluable population included all participants who received at least one tocilizumab injection and had at least one PK sample with detectable results taken at any time during the study.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Overall Number of Participants Analyzed 100 49
Mean (Standard Deviation)
Unit of Measure: mcg*day/mL
499.2  (210.4) 227.2  (165.4)
8.Secondary Outcome
Title Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab
Hide Description Cmax,ss is maximum model-predicted serum steady state concentration of tocilizumab measured in micrograms per milliliter (mcg/mL).
Time Frame Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Overall Number of Participants Analyzed 100 49
Mean (Standard Deviation)
Unit of Measure: mcg/mL
73  (30.4) 19.3  (12.8)
9.Secondary Outcome
Title Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab
Hide Description Cmin,ss is minimum model-predicted serum steady state concentration of tocilizumab measured in mcg/mL.
Time Frame Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Overall Number of Participants Analyzed 100 49
Mean (Standard Deviation)
Unit of Measure: mcg/mL
68.1  (29.5) 11.1  (10.3)
10.Secondary Outcome
Title Minimum Observed Serum Concentration (Ctrough) of Tocilizumab
Hide Description Ctrough is minimum observed serum concentration of tocilizumab measured in mcg/mL.
Time Frame Predose (Hour 0) at Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Overall Number of Participants Analyzed 99 48
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Baseline (n= 99, 48) 0.07  (0.72) 0.00  (0.02)
Week 52 (n= 72, 33) 67.93  (34.40) 12.22  (10.02)
11.Secondary Outcome
Title Serum Interleukin-6 (IL-6) Level
Hide Description [Not Specified]
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 50 51
Mean (Standard Deviation)
Unit of Measure: picograms per milliliter (pg/mL)
Baseline (n=91,44,50,47) 8.79  (10.01) 16.29  (31.23) 12.73  (18.04) 8.31  (9.47)
Week 52 (n=69,32,28,30) 65.99  (84.92) 52.70  (33.10) 35.96  (149.65) 10.85  (15.17)
12.Secondary Outcome
Title Serum Soluble IL-6 Receptor (sIL-6R) Level
Hide Description [Not Specified]
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 50 51
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
Baseline (n=99,48,50,50) 51.34  (61.98) 50.82  (63.51) 42.07  (11.32) 40.37  (10.84)
Week 52 (n=73,33,33,31) 600.53  (217.52) 464.30  (153.64) 76.44  (149.20) 64.80  (105.13)
13.Secondary Outcome
Title Erythrocyte Sedimentation Rate (ESR)
Hide Description ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 50 51
Median (Inter-Quartile Range)
Unit of Measure: mm/hr
Baseline (n=99,49,50,51)
19.00
(10.00 to 35.00)
15.00
(10.00 to 30.00)
23.00
(9.00 to 36.00)
20.00
(8.00 to 38.00)
Week 52 (n=76,35,35,33)
3.00
(2.00 to 5.00)
5.00
(2.00 to 7.00)
20.00
(11.00 to 36.00)
24.00
(10.00 to 37.00)
14.Secondary Outcome
Title C-Reactive Protein (CRP) Level
Hide Description The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'n' signifies the number of participants evaluable at specified time point for different arms, respectively.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 100 49 50 51
Median (Inter-Quartile Range)
Unit of Measure: milligrams per liter (mg/L)
Baseline (n=100,49,50,51)
3.67
(1.02 to 9.26)
4.52
(1.55 to 9.75)
3.64
(1.20 to 9.59)
3.56
(1.17 to 7.24)
Week 52 (n=76,35,35,33)
0.30
(0.20 to 0.59)
0.33
(0.20 to 0.72)
4.90
(2.25 to 9.25)
8.12
(2.02 to 14.40)
15.Secondary Outcome
Title Percentage of Participants With Anti-Tocilizumab Antibodies
Hide Description All samples were tested by screening assay, and those samples that were positive were further analyzed by a confirmation assay to confirm specificity. Percentage of participants who has a positive confirmation assay result any time after the initial drug administration with a negative confirmation assay result at baseline was reported.
Time Frame Baseline up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Here, 'Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper
Hide Arm/Group Description:
Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.
Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks.
Overall Number of Participants Analyzed 95 46 49 47
Measure Type: Number
Unit of Measure: percentage of participants
1.1 6.5 2.0 2.1
Time Frame Up to 156 weeks
Adverse Event Reporting Description Safety population
 
Arm/Group Title Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper Part 2: No Tocilizumab (Placebo in Part 1) Part 2: No Tocilizumab (Tocilizumab in Part 1) Part 2: Tocilizumab (Placebo in Part 1) Part 2: Tocilizumab (Tocilizumab in Part 1)
Hide Arm/Group Description Participants received tocilizumab at a dose of 162 mg as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52. Participants received tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses for 52 weeks. Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received placebo during Part 1 (Weeks 1 to 52). Participants did not receive tocilizumab in Part 2 from Week 52 up to Week 156. These participants received tocilizumab during Part 1 (Weeks 1 to 52). Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received placebo during Part 1 (Weeks 1 to 52). Participants received open-label tocilizumab as determined by the investigator during Part 2 of the study (from Week 52 up to Week 156). These participants received tocilizumab during Part 1 (Weeks 1 to 52).
All-Cause Mortality
Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper Part 2: No Tocilizumab (Placebo in Part 1) Part 2: No Tocilizumab (Tocilizumab in Part 1) Part 2: Tocilizumab (Placebo in Part 1) Part 2: Tocilizumab (Tocilizumab in Part 1)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper Part 2: No Tocilizumab (Placebo in Part 1) Part 2: No Tocilizumab (Tocilizumab in Part 1) Part 2: Tocilizumab (Placebo in Part 1) Part 2: Tocilizumab (Tocilizumab in Part 1)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/100 (15.00%)   7/49 (14.29%)   11/50 (22.00%)   13/51 (25.49%)   7/40 (17.50%)   11/58 (18.97%)   18/50 (36.00%)   23/67 (34.33%) 
Blood and lymphatic system disorders                 
Anaemia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Lymphocytosis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
White blood cell disorder * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Cardiac disorders                 
Aortic valve stenosis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Cardiac failure * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  1/40 (2.50%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Cardiac failure chronic * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Supraventricular tachycardia * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Tachyarrhythmia * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Angina pectoris * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  1/67 (1.49%) 
Atrial fibrillation * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  1/67 (1.49%) 
Acute myocardial infarction * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Angina unstable * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Myocardial ischaemia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Sinus node dysfunction * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Tachycardia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Eye disorders                 
Glaucoma * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  1/40 (2.50%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Cataract * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Visual acuity reduced transiently * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Gastrointestinal disorders                 
Gastritis erosive * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Stomatitis * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Diarrhoea * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Abdominal pain * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Anal haemorrhage * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Constipation * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Duodenal perforation * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Incarcerated inguinal hernia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Large intestine polyp * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Pancreatitis acute * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
General disorders                 
Non-cardiac chest pain * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  1/67 (1.49%) 
Chest pain * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Impaired healing * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Hepatobiliary disorders                 
Cholecystitis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Immune system disorders                 
Drug hypersensitivity * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Hypersensitivity * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Infections and infestations                 
Erysipelas * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Pneumonia * 1  1/100 (1.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Gastroenteritis * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  2/51 (3.92%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Genital herpes zoster * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Herpes zoster * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  2/51 (3.92%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Respiratory tract infection * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Cellulitis * 1  1/100 (1.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Chronic sinusitis * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Pneumonia haemophilus * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Pyelonephritis * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Urinary tract infection * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Urosepsis * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  2/50 (4.00%)  0/67 (0.00%) 
Cholangitis infective * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Device related infection * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Respiratory tract infection viral * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Injury, poisoning and procedural complications                 
Postoperative wound complication * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Alcohol poisoning * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Laceration * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Tendon rupture * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Meniscus injury * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Ankle fracture * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Cartilage injury * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Fracture displacement * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Hand fracture * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Lumbar vertebral fracture * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Procedural haemorrhage * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Upper limb fracture * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Investigations                 
Hepatic enzyme increased * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Troponin increased * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Metabolism and nutrition disorders                 
Hypokalaemia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Hyponatraemia * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Fibromyalgia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Osteoarthritis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  2/67 (2.99%) 
Tendon pain * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Arthritis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  1/67 (1.49%) 
Chondropathy * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Intervertebral disc protrusion * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Joint effusion * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Lumbar spinal stenosis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Musculoskeletal pain * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Osteonecrosis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Osteonecrosis of jaw * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Breast cancer * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Malignant melanoma * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Ovarian adenoma * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Invasive ductal breast carcinoma * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Prostate cancer * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Small cell lung cancer metastatic * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Squamous cell carcinoma of the vulva * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Nervous system disorders                 
Paraesthesia * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Syncope * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  1/40 (2.50%)  1/58 (1.72%)  0/50 (0.00%)  1/67 (1.49%) 
Transient ischaemic attack * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Headache * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Thrombotic stroke * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Cerebrovascular accident * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  2/50 (4.00%)  0/67 (0.00%) 
Carotid artery stenosis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Cerebellar infarction * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Facial paresis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Ischaemic stroke * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Presyncope * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Sciatica * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Visual field defect * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Psychiatric disorders                 
Anxiety * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Stress * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Anxiety disorder * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Renal and urinary disorders                 
Renal impairment * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Nephrolithiasis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Acute kidney injury * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Respiratory, thoracic and mediastinal disorders                 
Nasal inflammation * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Oropharyngeal pain * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Asthma * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Dyspnoea exertional * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Pleural effusion * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Pulmonary embolism * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Dyspnoea * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Surgical and medical procedures                 
Cancer surgery * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Vascular disorders                 
Hypertension * 1  0/100 (0.00%)  0/49 (0.00%)  1/50 (2.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Temporal arteritis * 1  1/100 (1.00%)  1/49 (2.04%)  1/50 (2.00%)  1/51 (1.96%)  1/40 (2.50%)  0/58 (0.00%)  2/50 (4.00%)  3/67 (4.48%) 
Deep vein thrombosis * 1  1/100 (1.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Hypertensive crisis * 1  2/100 (2.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Dry gangrene * 1  0/100 (0.00%)  1/49 (2.04%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Haematoma * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  2/67 (2.99%) 
Aortic aneurysm rupture * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Aortic dissection * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Intermittent claudication * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
Peripheral artery occlusion * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  1/50 (2.00%)  0/67 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Tocilizumab qw + 26 Weeks Prednisone Taper Part 1: Tocilizumab q2w + 26 Weeks Prednisone Taper Part 1: Placebo + 26 Weeks Prednisone Taper Part 1: Placebo + 52 Weeks Prednisone Taper Part 2: No Tocilizumab (Placebo in Part 1) Part 2: No Tocilizumab (Tocilizumab in Part 1) Part 2: Tocilizumab (Placebo in Part 1) Part 2: Tocilizumab (Tocilizumab in Part 1)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   87/100 (87.00%)   44/49 (89.80%)   47/50 (94.00%)   44/51 (86.27%)   33/40 (82.50%)   50/58 (86.21%)   44/50 (88.00%)   61/67 (91.04%) 
Cardiac disorders                 
Palpitations * 1  2/100 (2.00%)  2/49 (4.08%)  4/50 (8.00%)  2/51 (3.92%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Ear and labyrinth disorders                 
Vertigo * 1  2/100 (2.00%)  1/49 (2.04%)  3/50 (6.00%)  1/51 (1.96%)  2/40 (5.00%)  2/58 (3.45%)  2/50 (4.00%)  2/67 (2.99%) 
Tinnitus * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  0/58 (0.00%)  2/50 (4.00%)  1/67 (1.49%) 
Eye disorders                 
Cataract * 1  5/100 (5.00%)  1/49 (2.04%)  3/50 (6.00%)  4/51 (7.84%)  2/40 (5.00%)  1/58 (1.72%)  3/50 (6.00%)  3/67 (4.48%) 
Dry eye * 1  1/100 (1.00%)  3/49 (6.12%)  1/50 (2.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Gastrointestinal disorders                 
Abdominal pain upper * 1  3/100 (3.00%)  3/49 (6.12%)  3/50 (6.00%)  4/51 (7.84%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Constipation * 1  0/100 (0.00%)  1/49 (2.04%)  3/50 (6.00%)  4/51 (7.84%)  1/40 (2.50%)  0/58 (0.00%)  3/50 (6.00%)  1/67 (1.49%) 
Diarrhoea * 1  12/100 (12.00%)  3/49 (6.12%)  8/50 (16.00%)  5/51 (9.80%)  2/40 (5.00%)  2/58 (3.45%)  7/50 (14.00%)  5/67 (7.46%) 
Dyspepsia * 1  0/100 (0.00%)  0/49 (0.00%)  4/50 (8.00%)  1/51 (1.96%)  0/40 (0.00%)  2/58 (3.45%)  3/50 (6.00%)  0/67 (0.00%) 
Nausea * 1  8/100 (8.00%)  2/49 (4.08%)  5/50 (10.00%)  4/51 (7.84%)  1/40 (2.50%)  0/58 (0.00%)  5/50 (10.00%)  3/67 (4.48%) 
Vomiting * 1  2/100 (2.00%)  2/49 (4.08%)  2/50 (4.00%)  3/51 (5.88%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Gastritis * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  1/58 (1.72%)  0/50 (0.00%)  1/67 (1.49%) 
Gastrooesophageal reflux disease * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  5/67 (7.46%) 
Toothache * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  0/58 (0.00%)  0/50 (0.00%)  2/67 (2.99%) 
General disorders                 
Asthenia * 1  5/100 (5.00%)  3/49 (6.12%)  5/50 (10.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Fatigue * 1  8/100 (8.00%)  5/49 (10.20%)  8/50 (16.00%)  3/51 (5.88%)  2/40 (5.00%)  2/58 (3.45%)  6/50 (12.00%)  6/67 (8.96%) 
Non-cardiac chest pain * 1  1/100 (1.00%)  2/49 (4.08%)  1/50 (2.00%)  3/51 (5.88%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Oedema peripheral * 1  16/100 (16.00%)  12/49 (24.49%)  8/50 (16.00%)  6/51 (11.76%)  1/40 (2.50%)  2/58 (3.45%)  5/50 (10.00%)  4/67 (5.97%) 
Discomfort * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  3/50 (6.00%)  1/67 (1.49%) 
Gait disturbance * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  0/58 (0.00%)  0/50 (0.00%)  1/67 (1.49%) 
Immune system disorders                 
Drug hypersensitivity * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  0/58 (0.00%)  1/50 (2.00%)  2/67 (2.99%) 
Infections and infestations                 
Bronchitis * 1  8/100 (8.00%)  4/49 (8.16%)  5/50 (10.00%)  5/51 (9.80%)  4/40 (10.00%)  9/58 (15.52%)  3/50 (6.00%)  9/67 (13.43%) 
Conjunctivitis * 1  4/100 (4.00%)  1/49 (2.04%)  4/50 (8.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  4/50 (8.00%)  3/67 (4.48%) 
Cystitis * 1  7/100 (7.00%)  0/49 (0.00%)  2/50 (4.00%)  3/51 (5.88%)  2/40 (5.00%)  3/58 (5.17%)  4/50 (8.00%)  3/67 (4.48%) 
Gastroenteritis * 1  3/100 (3.00%)  4/49 (8.16%)  4/50 (8.00%)  3/51 (5.88%)  0/40 (0.00%)  2/58 (3.45%)  3/50 (6.00%)  4/67 (5.97%) 
Nasopharyngitis * 1  29/100 (29.00%)  12/49 (24.49%)  9/50 (18.00%)  13/51 (25.49%)  5/40 (12.50%)  13/58 (22.41%)  14/50 (28.00%)  22/67 (32.84%) 
Oral herpes * 1  4/100 (4.00%)  5/49 (10.20%)  3/50 (6.00%)  2/51 (3.92%)  2/40 (5.00%)  2/58 (3.45%)  1/50 (2.00%)  2/67 (2.99%) 
Pharyngitis * 1  4/100 (4.00%)  0/49 (0.00%)  1/50 (2.00%)  3/51 (5.88%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Rhinitis * 1  6/100 (6.00%)  4/49 (8.16%)  2/50 (4.00%)  3/51 (5.88%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Sinusitis * 1  3/100 (3.00%)  4/49 (8.16%)  1/50 (2.00%)  2/51 (3.92%)  2/40 (5.00%)  1/58 (1.72%)  1/50 (2.00%)  6/67 (8.96%) 
Upper respiratory tract infection * 1  10/100 (10.00%)  6/49 (12.24%)  5/50 (10.00%)  7/51 (13.73%)  1/40 (2.50%)  2/58 (3.45%)  7/50 (14.00%)  2/67 (2.99%) 
Urinary tract infection * 1  10/100 (10.00%)  4/49 (8.16%)  2/50 (4.00%)  4/51 (7.84%)  1/40 (2.50%)  4/58 (6.90%)  10/50 (20.00%)  10/67 (14.93%) 
Herpes zoster * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  4/58 (6.90%)  4/50 (8.00%)  2/67 (2.99%) 
Influenza * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  2/58 (3.45%)  3/50 (6.00%)  0/67 (0.00%) 
Lower respiratory tract infection * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  0/58 (0.00%)  1/50 (2.00%)  1/67 (1.49%) 
Respiratory tract infection * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  4/40 (10.00%)  2/58 (3.45%)  1/50 (2.00%)  4/67 (5.97%) 
Injury, poisoning and procedural complications                 
Fall * 1  7/100 (7.00%)  2/49 (4.08%)  2/50 (4.00%)  2/51 (3.92%)  4/40 (10.00%)  2/58 (3.45%)  2/50 (4.00%)  9/67 (13.43%) 
Arthropod bite * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  1/50 (2.00%)  4/67 (5.97%) 
Limb injury * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  0/58 (0.00%)  1/50 (2.00%)  3/67 (4.48%) 
Investigations                 
Alanine aminotransferase increased * 1  5/100 (5.00%)  2/49 (4.08%)  2/50 (4.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  3/50 (6.00%)  0/67 (0.00%) 
Complement factor C3 decreased * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  4/50 (8.00%)  0/67 (0.00%) 
Complement factor C4 decreased * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  3/50 (6.00%)  1/67 (1.49%) 
Metabolism and nutrition disorders                 
Hypercholesterolaemia * 1  2/100 (2.00%)  3/49 (6.12%)  0/50 (0.00%)  1/51 (1.96%)  0/40 (0.00%)  2/58 (3.45%)  1/50 (2.00%)  5/67 (7.46%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia * 1  13/100 (13.00%)  8/49 (16.33%)  10/50 (20.00%)  8/51 (15.69%)  7/40 (17.50%)  10/58 (17.24%)  10/50 (20.00%)  12/67 (17.91%) 
Back pain * 1  14/100 (14.00%)  7/49 (14.29%)  7/50 (14.00%)  10/51 (19.61%)  3/40 (7.50%)  4/58 (6.90%)  8/50 (16.00%)  7/67 (10.45%) 
Bursitis * 1  1/100 (1.00%)  4/49 (8.16%)  2/50 (4.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Muscle spasms * 1  4/100 (4.00%)  6/49 (12.24%)  6/50 (12.00%)  4/51 (7.84%)  0/40 (0.00%)  0/58 (0.00%)  5/50 (10.00%)  6/67 (8.96%) 
Musculoskeletal pain * 1  12/100 (12.00%)  6/49 (12.24%)  5/50 (10.00%)  2/51 (3.92%)  4/40 (10.00%)  6/58 (10.34%)  4/50 (8.00%)  4/67 (5.97%) 
Myalgia * 1  9/100 (9.00%)  4/49 (8.16%)  4/50 (8.00%)  4/51 (7.84%)  1/40 (2.50%)  0/58 (0.00%)  3/50 (6.00%)  2/67 (2.99%) 
Neck pain * 1  6/100 (6.00%)  1/49 (2.04%)  2/50 (4.00%)  4/51 (7.84%)  2/40 (5.00%)  1/58 (1.72%)  3/50 (6.00%)  1/67 (1.49%) 
Osteoarthritis * 1  7/100 (7.00%)  2/49 (4.08%)  3/50 (6.00%)  3/51 (5.88%)  1/40 (2.50%)  2/58 (3.45%)  6/50 (12.00%)  6/67 (8.96%) 
Pain in extremity * 1  8/100 (8.00%)  5/49 (10.20%)  5/50 (10.00%)  5/51 (9.80%)  1/40 (2.50%)  5/58 (8.62%)  4/50 (8.00%)  7/67 (10.45%) 
Osteopenia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  3/58 (5.17%)  0/50 (0.00%)  0/67 (0.00%) 
Rotator cuff syndrome * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  2/58 (3.45%)  5/50 (10.00%)  3/67 (4.48%) 
Nervous system disorders                 
Dizziness * 1  6/100 (6.00%)  10/49 (20.41%)  6/50 (12.00%)  8/51 (15.69%)  2/40 (5.00%)  0/58 (0.00%)  5/50 (10.00%)  4/67 (5.97%) 
Headache * 1  27/100 (27.00%)  10/49 (20.41%)  16/50 (32.00%)  12/51 (23.53%)  2/40 (5.00%)  8/58 (13.79%)  8/50 (16.00%)  6/67 (8.96%) 
Paraesthesia * 1  4/100 (4.00%)  2/49 (4.08%)  4/50 (8.00%)  4/51 (7.84%)  0/40 (0.00%)  2/58 (3.45%)  1/50 (2.00%)  5/67 (7.46%) 
Tremor * 1  0/100 (0.00%)  0/49 (0.00%)  3/50 (6.00%)  3/51 (5.88%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Carpal tunnel syndrome * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  1/58 (1.72%)  3/50 (6.00%)  3/67 (4.48%) 
Sciatica * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  2/58 (3.45%)  2/50 (4.00%)  5/67 (7.46%) 
Syncope * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  1/58 (1.72%)  2/50 (4.00%)  1/67 (1.49%) 
Psychiatric disorders                 
Anxiety * 1  2/100 (2.00%)  1/49 (2.04%)  6/50 (12.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Depression * 1  3/100 (3.00%)  2/49 (4.08%)  3/50 (6.00%)  1/51 (1.96%)  1/40 (2.50%)  0/58 (0.00%)  4/50 (8.00%)  0/67 (0.00%) 
Insomnia * 1  4/100 (4.00%)  1/49 (2.04%)  4/50 (8.00%)  4/51 (7.84%)  0/40 (0.00%)  2/58 (3.45%)  2/50 (4.00%)  4/67 (5.97%) 
Sleep disorder * 1  1/100 (1.00%)  3/49 (6.12%)  1/50 (2.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Cough * 1  6/100 (6.00%)  3/49 (6.12%)  7/50 (14.00%)  3/51 (5.88%)  2/40 (5.00%)  4/58 (6.90%)  7/50 (14.00%)  4/67 (5.97%) 
Dyspnoea * 1  3/100 (3.00%)  3/49 (6.12%)  1/50 (2.00%)  3/51 (5.88%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Dyspnoea exertional * 1  1/100 (1.00%)  0/49 (0.00%)  3/50 (6.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  3/50 (6.00%)  0/67 (0.00%) 
Epistaxis * 1  3/100 (3.00%)  1/49 (2.04%)  4/50 (8.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  4/50 (8.00%)  3/67 (4.48%) 
Oropharyngeal pain * 1  7/100 (7.00%)  4/49 (8.16%)  4/50 (8.00%)  8/51 (15.69%)  2/40 (5.00%)  2/58 (3.45%)  2/50 (4.00%)  4/67 (5.97%) 
Dysphonia * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  3/50 (6.00%)  0/67 (0.00%) 
Pulmonary mass * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  2/40 (5.00%)  1/58 (1.72%)  0/50 (0.00%)  0/67 (0.00%) 
Rhinorrhoea * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  3/58 (5.17%)  1/50 (2.00%)  0/67 (0.00%) 
Skin and subcutaneous tissue disorders                 
Alopecia * 1  5/100 (5.00%)  7/49 (14.29%)  3/50 (6.00%)  5/51 (9.80%)  0/40 (0.00%)  0/58 (0.00%)  4/50 (8.00%)  2/67 (2.99%) 
Dry skin * 1  2/100 (2.00%)  3/49 (6.12%)  0/50 (0.00%)  0/51 (0.00%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Ecchymosis * 1  0/100 (0.00%)  2/49 (4.08%)  1/50 (2.00%)  3/51 (5.88%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Night sweats * 1  1/100 (1.00%)  3/49 (6.12%)  1/50 (2.00%)  1/51 (1.96%)  0/40 (0.00%)  2/58 (3.45%)  1/50 (2.00%)  4/67 (5.97%) 
Pruritus * 1  2/100 (2.00%)  4/49 (8.16%)  1/50 (2.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Rash * 1  7/100 (7.00%)  5/49 (10.20%)  4/50 (8.00%)  2/51 (3.92%)  2/40 (5.00%)  2/58 (3.45%)  0/50 (0.00%)  5/67 (7.46%) 
Eczema * 1  0/100 (0.00%)  0/49 (0.00%)  0/50 (0.00%)  0/51 (0.00%)  1/40 (2.50%)  3/58 (5.17%)  2/50 (4.00%)  1/67 (1.49%) 
Vascular disorders                 
Haematoma * 1  5/100 (5.00%)  3/49 (6.12%)  3/50 (6.00%)  1/51 (1.96%)  0/40 (0.00%)  0/58 (0.00%)  0/50 (0.00%)  0/67 (0.00%) 
Hypertension * 1  12/100 (12.00%)  6/49 (12.24%)  4/50 (8.00%)  4/51 (7.84%)  1/40 (2.50%)  7/58 (12.07%)  7/50 (14.00%)  8/67 (11.94%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01791153     History of Changes
Other Study ID Numbers: WA28119
2011-006022-25 ( EudraCT Number )
First Submitted: February 12, 2013
First Posted: February 13, 2013
Results First Submitted: April 10, 2017
Results First Posted: May 18, 2017
Last Update Posted: June 18, 2019