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A Study to Assess Efficacy With Respect to Clinical Improvement in Disease Activity and Safety of Tocilizumab in Patients Wtih Active Rheumatoid Arthritis.

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: NCT00754559
Recruitment Status : Completed
First Posted : September 18, 2008
Results First Posted : June 10, 2014
Last Update Posted : February 8, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Intervention Drug: Tocilizumab
Enrollment 286
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 milligrams/kilogram (mg/kg) intravenously (iv) every 4 weeks for a total of 6 infusions.
Period Title: Overall Study
Started 286
Completed 239
Not Completed 47
Reason Not Completed
Adverse Event             15
Protocol Violation             11
Lack of Efficacy             10
Lost to Follow-up             2
Administrative reason             1
Other             5
Withdrawal by Subject             3
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Baseline Participants 286
Hide Baseline Analysis Population Description
All treated participants were included in the safety population as well as the intent to-treat (ITT) population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 286 participants
54.9  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 286 participants
Female
216
  75.5%
Male
70
  24.5%
1.Primary Outcome
Title Percentage of Participants With Low Disease Activity Score at Week 24
Hide Description Low Disease Activity Score (LDAS) is defined as Disease Activity score less than or equal to (≤ ) 3.2. Disease activity score 28 (DAS28) was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and global health assessment (participant rated global assessment of disease activity using 100-mm Visual analog scale [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
57
(51 to 62.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab
Comments Null hypothesis: Proportion of participants reaching LDAS (≤ 3.2) at Week 24 equals (=) expected proportion of 42%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Exact Binomial Test
Comments [Not Specified]
2.Secondary Outcome
Title Absolute Changes in DAS28 From Baseline
Hide Description DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant rated global assessment of disease activity using 100-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 = low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.
Time Frame Weeks 1, 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with a DAS28 value at baseline were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 274
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 1 -1.31  (1.1)
Week 2 -2.1  (1.2)
Week 4 -2.4  (1.2)
Week 8 -2.8  (1.3)
Week 12 -3.2  (1.4)
Week 16 -3.2  (1.4)
Week 20 -3.3  (1.4)
Week 24 -3.4  (1.4)
3.Secondary Outcome
Title Percentage of Participants With a Response at Week 24 by European League Against Rheumatism (EULAR) Category
Hide Description The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤ 0.6 or change from baseline >0.6 and ≤1.2 with DAS28 >5.1.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Measure Type: Number
Unit of Measure: Percentage of Participants
Good 54.9
Moderate 20.3
None 24.8
4.Secondary Outcome
Title Percentage of Participants With a DAS28 Response at Weeks 4 and 24
Hide Description DAS28 calculated from the number of swollen joints and painful joints using the 28-joint count, the ESR and participant's global assessment (PGA) of disease activity (participant rated arthritis activity assessment using VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2 = low disease activity, DAS28 <2.6 = remission and a clinically significant (CS) reduction was defined as ≥1.2.
Time Frame Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population;
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 4, CS reduction
75.2
(69.7 to 80.1)
Week 4, Remission
23.1
(18.3 to 28.4)
Week 4, CS reduction or remission
76.6
(71.2 to 81.4)
Week 4, LDAS
40.9
(35.2 to 46.9)
Week 24, CS reduction
74.5
(69.0 to 79.4)
Week 24, Remission
47.6
(41.6 to 53.5)
Week 24, CS reduction or remission
76.6
(71.2 to 81.4)
Week 24, LDAS
57.0
(51.0 to 62.8)
5.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 20%, 50%, or 70% (ACR20/ACR50/ACR70) Response
Hide Description ACR20/50/70 response: ≥20%, 50%, or 70% improvement, respectively, in swollen and tender joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and C-Reactive Protein (CRP).
Time Frame Weeks 1, 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 1 ACR20
25.2
(20.3 to 30.6)
Week 1 ACR50
7.0
(4.3 to 10.6)
Week 1 ACR70
2.4
(1.0 to 5.0)
Week 2 ACR20
41.3
(35.5 to 47.2)
Week 2 ACR50
14.7
(10.8 to 19.3)
Week 2 ACR70
4.9
(2.7 to 8.1)
Week 4 ACR20
50.0
(44.1 to 55.9)
Week 4 ACR50
25.5
(20.6 to 31.0)
Week 4 ACR70
12.2
(8.7 to 16.6)
Week 8 ACR20
64.3
(58.5 to 69.9)
Week 8 ACR50
37.4
(31.8 to 43.3)
Week 8 ACR70
17.1
(13.0 to 22.0)
Week 12 ACR20
69.6
(63.9 to 74.9)
Week 12 ACR50
48.6
(42.7 to 54.6)
Week 12 ACR70
26.2
(21.2 to 31.7)
Week 16 ACR20
67.5
(61.7 to 72.9)
Week 16 ACR50
49.0
(43.0 to 54.9)
Week 16 ACR70
29.4
(24.2 to 35.0)
Week 20 ACR20
67.8
(62.1 to 73.2)
Week 20 ACR50
49.7
(43.7 to 55.6)
Week 20 ACR70
33.9
(28.4 to 39.7)
Week 24 ACR20
65.0
(59.2 to 70.6)
Week 24 ACR50
50.7
(44.7 to 56.6)
Week 24 ACR70
33.9
(28.4 to 39.7)
6.Secondary Outcome
Title Change From Baseline in Swollen and Tender Joint Counts at Week 24
Hide Description

Swollen joint count: 66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.

Tender joint counts: 68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; missing data were imputed using last observation carried forward (LOCF).
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (95% Confidence Interval)
Unit of Measure: Joints
Number of swollen joints
-9.6
(-10.4 to -8.7)
Number of tender joints
-13.4
(-14.7 to -12.1)
7.Secondary Outcome
Title Change From Baseline in the Levels of C-Reactive Protein at Week 24
Hide Description The serum concentration of CRP is measured in mg/L. A reduction in the level was considered an improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (95% Confidence Interval)
Unit of Measure: mg/L
-20.1
(-23.7 to -16.6)
8.Secondary Outcome
Title Change From Baseline in Participant's Global Assessment of Pain (VAS) at Week 24
Hide Description Participant's global assessment of pain was assessed using a 100-mm horizontal VAS (0 to 100 mm) with 0=pain absent and 100=unbearable pain. Participants responded by placing a mark on the line to indicate their current level of pain.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (95% Confidence Interval)
Unit of Measure: mm
-36.2
(-39.6 to -32.7)
9.Secondary Outcome
Title Change From Baseline in Participant and Physician Assessment of Global Disease Activity (VAS) at Week 24
Hide Description

Participant's global assessment of disease activity was an overall assessment of their current disease activity on a 100-mm horizontal VAS scale (left-hand extreme: "no disease activity"; right-hand extreme: "maximum disease activity").

Physician's global assessment of disease activity was measured as participant's current disease activity on a 100-mm horizontal VAS scale (left hand extreme: "no disease activity"; right-hand extreme: "maximum disease activity").

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (95% Confidence Interval)
Unit of Measure: mm
Participant's assessment
-35.9
(-39.5 to -32.4)
Physician's assessment
-44.9
(-47.7 to -42.1)
10.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index (CDAI) Score
Hide Description

CDAI was calculated according to the following formula:

CDAI = Number of swollen joints (plus) + Number of tender joints + VAS disease activity participant assessment + VAS disease activity investigator assessment. The maximum score was 334 (66 joints + 68 joints + 100 mm + 100 mm); higher scores indicated higher disease activity.

Time Frame Weeks 1, 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; only participants with values for CDAI at baseline and the respective visit were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 1 -8.4  (12.1)
Week 2 -13.3  (12.4)
Week 4 -15.6  (13.4)
Week 8 -19.7  (13.2)
Week 12 -22.4  (13.4)
Week 16 -22.4  (13.8)
Week 20 -22.7  (13.3)
Week 24 -24.2  (12.9)
11.Secondary Outcome
Title Change From Baseline in HAQ-DI at Week 24
Hide Description HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.48  (0.60)
12.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24
Hide Description FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.6  (11.1)
13.Secondary Outcome
Title Change From Baseline in Short Form-36 (SF-36) Score at Week 24
Hide Description SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Absolute change was defined as the change from baseline to Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical functioning 18.4  (24.6)
Role physical 16.5  (21.6)
Bodily pain 25.0  (22.3)
General health perception 11.9  (18.7)
Vitality 18.0  (20.2)
Social functioning 13.8  (27.2)
Role emotional 13.9  (50.1)
Mental health 10.3  (19.1)
14.Secondary Outcome
Title Participant's Global Assessment of Pain as Assessed by Patient Take Home Form (PTHF)
Hide Description Participant's were asked to state the worst level of pain felt in the past 24 hours using a 100-mm horizontal VAS (0 to 100 mm) with 0=no pain and 100=unbearable pain. Participants responded by placing a mark on the line to indicate their level of pain. Participants were asked to document their response during the first 4 treatment weeks at approximately the same time every day.
Time Frame Baseline and Weeks 1, 2, and 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: mm
Baseline 60.7  (23.1)
Week 1 48.6  (25.2)
Week 2 41.9  (25.4)
Week 4 36.3  (26.7)
Change at Week 1 -12.0  (22.3)
Change at Week 2 -18.7  (24.9)
Change at Week 4 -24.4  (27.4)
15.Secondary Outcome
Title Duration of Morning Stiffness as Assessed Using PTHF
Hide Description Duration of morning stiffness: participants were asked 'how long did your morning stiffness last from the time you woke up yesterday' and the response was provided in minutes and hours. Participants were asked to document their response during the first 4 treatment weeks at approximately the same time every day.
Time Frame Baseline, Weeks 1, 2, and 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: hours
Baseline 2.4  (2.8)
Week 1 1.8  (2.3)
Week 2 1.5  (1.8)
Week 4 1.2  (1.5)
Change at Week 1 -0.6  (1.8)
Change at Week 2 -0.9  (2.1)
Change at Week 4 -1.2  (2.3)
16.Secondary Outcome
Title Participant Assessment of Fatigue/Tiredness as Assessed Using PTHF
Hide Description Participants were asked to assess their overall level of fatigue/tiredness during the previous 24 hours using a 100-mm horizontal VAS with 0=none and 100=very severe. Participants responded by placing a mark on the line to indicate their current level of fatigue. Participants were asked to document their response during the first 4 treatment weeks at approximately the same time every day.
Time Frame Baseline and Weeks 1, 2 and 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Missing data were imputed using LOCF.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: mm
Baseline 52.9  (26.9)
Week 1 42.2  (26.2)
Week 2 36.3  (26.5)
Week 4 30.6  (26.0)
Change at Week 1 -10.6  (22.0)
Change at Week 2 -16.6  (24.1)
Change at Week 4 -22.2  (26.5)
17.Secondary Outcome
Title Treatment Satisfaction Questionnaire for Medication (TSQM) Score
Hide Description The TSQM is a general measure of participants treatment satisfaction and consists of 14 questions that result in 4 subscales: "effectiveness", "side-effects", "convenience" and "global satisfaction". All subscale scores range from 0 to 100%, with 100% being the best possible result.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: units on a scale
Percent Effectiveness 69.4  (28.3)
Percent Side-effects 88.7  (21.7)
Percent Convenience 72.4  (20.8)
Percent Global satisfaction 74.7  (25.9)
18.Secondary Outcome
Title Changes in Hemoglobin
Hide Description Hemoglobin levels were determined as a hematology parameter to measure changes in disease related anemia.
Time Frame Baseline, Weeks 1, 2, 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks up to week 20 for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: g/dL
Baseline 128.6  (13.1)
Week 1 132.2  (13.4)
Week 2 133.5  (13.1)
Week 4 133.5  (13.6)
Week 24 136.1  (13.7)
Change at Week 1 3.5  (6.8)
Change at Week 2 4.8  (6.5)
Change at Week 4 4.3  (8.0)
Change at Week 24 7.5  (9.7)
19.Secondary Outcome
Title Changes in C-Reactive Protein
Hide Description CRP is an acute phase inflammatory marker used as a measure of inflammation. A reduction in CRP is considered to be an improvement.
Time Frame Baseline, Weeks 1, 2 ,4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: mg/L
Baseline 23.1  (30.7)
Week 1 3.5  (6.6)
Week 2 2.4  (4.4)
Week 4 5.5  (14.8)
Week 24 3.0  (7.7)
Change at Week 1 -19.6  (29.4)
Change at Week 2 -20.7  (29.8)
Change at Week 4 -17.5  (27.7)
Change at Week 24 -20.1  (29.9)
20.Secondary Outcome
Title Changes in Erythrocyte Sedimentation Rate (ESR)
Hide Description ESR is an inflammation marker used to determine acute phase response.
Time Frame Baseline, Weeks 1, 2, 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 286
Mean (Standard Deviation)
Unit of Measure: mm/h
Baseline 37.4  (22.1)
Week 1 16.7  (14.2)
Week 2 10.6  (11.0)
Week 4 10.3  (13.5)
Week 24 7.1  (9.5)
Change at Week 1 -20.6  (17.9)
Change at Week 2 -26.7  (19.0)
Change at Week 4 -27.2  (18.6)
Change at Week 24 -30.3  (21.7)
21.Secondary Outcome
Title Percentage of Participants Withdrawing From Study Treatment Because of Insufficient Therapeutic Response
Hide Description Participants who withdrew from study drug due to other reasons were not taken into account.
Time Frame Weeks 1, 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; participants who withdrew from study drug due to other reaasons were not included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8mg /kg iv every 4 weeks for a total of 6 infusions.
Overall Number of Participants Analyzed 249
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.0
(1.9 to 7.3)
Time Frame Adverse events were reported throughout the study including any reactions that occurred within 24 hours after infusion.
Adverse Event Reporting Description An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
 
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg iv every 4 weeks for a total of 6 infusions.
All-Cause Mortality
Tocilizumab
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Tocilizumab
Affected / at Risk (%)
Total   32/286 (11.19%) 
Ear and labyrinth disorders   
Vertigo * 1  1/286 (0.35%) 
Endocrine disorders   
Hypothyroidism * 1  1/286 (0.35%) 
Gastrointestinal disorders   
Periodontitis  1  1/286 (0.35%) 
Vomiting  1  1/286 (0.35%) 
General disorders   
General physical health deterioration  1  1/286 (0.35%) 
Chest pain * 1  1/286 (0.35%) 
Infections and infestations   
Pneumonia  1  2/286 (0.70%) 
Abscess jaw  1  1/286 (0.35%) 
Bronchopneumonia  1  1/286 (0.35%) 
Herpes zoster  1  1/286 (0.35%) 
Osteomyelitis  1  1/286 (0.35%) 
Pharyngeal abscess  1  1/286 (0.35%) 
Postoperative wound infection  1  1/286 (0.35%) 
Septic shock  1  1/286 (0.35%) 
Injury, poisoning and procedural complications   
Lower limb fracture * 1  1/286 (0.35%) 
Overdose * 1  8/286 (2.80%) 
Investigations   
Low density lipoprotein increased  1  1/286 (0.35%) 
Alanine aminotransferase increased * 1  1/286 (0.35%) 
Aspartate aminotransferase increased * 1  1/286 (0.35%) 
Musculoskeletal and connective tissue disorders   
Bursitis  1  1/286 (0.35%) 
Tendonitis  1  1/286 (0.35%) 
Back pain * 1  1/286 (0.35%) 
Rheumatoid arthritis * 1  1/286 (0.35%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Non-Hodgkin's lymphoma  1  1/286 (0.35%) 
Bladder transitional cell carcinoma * 1  1/286 (0.35%) 
Nervous system disorders   
Multiple sclerosis relapse  1  1/286 (0.35%) 
Headache * 1  1/286 (0.35%) 
Pregnancy, puerperium and perinatal conditions   
Abortion * 1  1/286 (0.35%) 
Psychiatric disorders   
Post-traumatic stress disorder * 1  1/286 (0.35%) 
Renal and urinary disorders   
Renal failure acute  1  1/286 (0.35%) 
Respiratory, thoracic and mediastinal disorders   
Interstitial lung disease  1  1/286 (0.35%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tocilizumab
Affected / at Risk (%)
Total   242/286 (84.62%) 
Blood and lymphatic system disorders   
Eosinophilia  1  1/286 (0.35%) 
Haemolysis * 1  2/286 (0.70%) 
Intravascular haemolysis * 1  2/286 (0.70%) 
Leukopenia * 1  19/286 (6.64%) 
Neutropenia * 1  5/286 (1.75%) 
Thrombocytopenia * 1  5/286 (1.75%) 
Cardiac disorders   
Extrasystoles * 1  1/286 (0.35%) 
Palpitations * 1  2/286 (0.70%) 
Tachyarrhythmia * 1  1/286 (0.35%) 
Ear and labyrinth disorders   
Ear pain * 1  1/286 (0.35%) 
Tinnitus * 1  2/286 (0.70%) 
Vertigo * 1  4/286 (1.40%) 
Endocrine disorders   
Cushingoid * 1  1/286 (0.35%) 
Goitre * 1  2/286 (0.70%) 
Hypothyroidism * 1  1/286 (0.35%) 
Eye disorders   
Conjunctival haemorrhage * 1  2/286 (0.70%) 
Conjunctivitis * 1  6/286 (2.10%) 
Dry eye * 1  1/286 (0.35%) 
Eye inflammation * 1  1/286 (0.35%) 
Eyelid oedema * 1  1/286 (0.35%) 
Visual acuity reduced * 1  1/286 (0.35%) 
Gastrointestinal disorders   
Abdominal discomfort * 1  1/286 (0.35%) 
Abdominal distension * 1  1/286 (0.35%) 
Abdominal pain * 1  2/286 (0.70%) 
Abdominal pain upper * 1  4/286 (1.40%) 
Aphthous stomatitis * 1  3/286 (1.05%) 
Constipation * 1  2/286 (0.70%) 
Dental caries * 1  2/286 (0.70%) 
Diarrhoea * 1  16/286 (5.59%) 
Diarrhoea haemorrhagic * 1  1/286 (0.35%) 
Dry mouth * 1  1/286 (0.35%) 
Dyspepsia * 1  4/286 (1.40%) 
Enteritis * 1  2/286 (0.70%) 
Eructation * 1  1/286 (0.35%) 
Flatulence * 1  1/286 (0.35%) 
Gastric ulcer * 1  1/286 (0.35%) 
Gastritis * 1  2/286 (0.70%) 
Gastrooesophageal reflux disease * 1  1/286 (0.35%) 
Gingival bleeding * 1  1/286 (0.35%) 
Gingival erythema * 1  1/286 (0.35%) 
Loose tooth  1  1/286 (0.35%) 
Nausea * 1  9/286 (3.15%) 
Periodontitis * 1  5/286 (1.75%) 
Stomatitis * 1  3/286 (1.05%) 
Toothache * 1  1/286 (0.35%) 
Vomiting * 1  5/286 (1.75%) 
General disorders   
Chest pain * 1  2/286 (0.70%) 
Chills * 1  2/286 (0.70%) 
Discomfort * 1  3/286 (1.05%) 
Drug intolerance * 1  3/286 (1.05%) 
Fatigue * 1  13/286 (4.55%) 
General physical health deterioration * 1  1/286 (0.35%) 
Local swelling * 1  1/286 (0.35%) 
Malaise * 1  1/286 (0.35%) 
Mucosal inflammation * 1  1/286 (0.35%) 
Oedema * 1  1/286 (0.35%) 
Oedema peripheral * 1  6/286 (2.10%) 
Pitting oedema * 1  1/286 (0.35%) 
Thirst * 1  1/286 (0.35%) 
Hepatobiliary disorders   
Hepatotoxicity * 1  1/286 (0.35%) 
Immune system disorders   
Food allergy * 1  1/286 (0.35%) 
Hypersensitivity * 1  5/286 (1.75%) 
Seasonal allergy * 1  2/286 (0.70%) 
Infections and infestations   
Abscess jaw * 1  1/286 (0.35%) 
Abscess limb * 1  1/286 (0.35%) 
Acute tonsillitis * 1  1/286 (0.35%) 
Anal abscess * 1  1/286 (0.35%) 
Bacterial disease carrier * 1  1/286 (0.35%) 
Bacteriuria * 1  1/286 (0.35%) 
Bronchitis * 1  16/286 (5.59%) 
Bronchopneumonia * 1  2/286 (0.70%) 
Cellulitis * 1  1/286 (0.35%) 
Cystitis * 1  5/286 (1.75%) 
Eyelid infection * 1  1/286 (0.35%) 
Folliculitis * 1  3/286 (1.05%) 
Fungal skin infection * 1  1/286 (0.35%) 
Furuncle * 1  1/286 (0.35%) 
Gastroenteritis * 1  5/286 (1.75%) 
Gastrointestinal infection * 1  1/286 (0.35%) 
Herpes simplex * 1  1/286 (0.35%) 
Herpes virus infection  1  1/286 (0.35%) 
Herpes zoster * 1  2/286 (0.70%) 
Herpes zoster ophthalmic * 1  1/286 (0.35%) 
Influenza * 1  3/286 (1.05%) 
Lower respiratory tract infection viral * 1  1/286 (0.35%) 
Nasopharyngitis * 1  54/286 (18.88%) 
Onychomycosis * 1  2/286 (0.70%) 
Oral herpes * 1  6/286 (2.10%) 
Osteomyelitis * 1  1/286 (0.35%) 
Otitis media * 1  3/286 (1.05%) 
Paronychia * 1  1/286 (0.35%) 
Parotitis * 1  1/286 (0.35%) 
Peritonsillar abscess * 1  1/286 (0.35%) 
Pharyngeal abscess * 1  1/286 (0.35%) 
Pharyngitis * 1  4/286 (1.40%) 
Pneumonia * 1  2/286 (0.70%) 
Post procedural infection * 1  1/286 (0.35%) 
Postoperative wound infection * 1  1/286 (0.35%) 
Prostate infection * 1  1/286 (0.35%) 
Pulpitis dental * 1  2/286 (0.70%) 
Respiratory tract infection * 1  4/286 (1.40%) 
Rhinitis * 1  15/286 (5.24%) 
Septic shock * 1  1/286 (0.35%) 
Sinobronchitis * 1  1/286 (0.35%) 
Sinusitis * 1  8/286 (2.80%) 
Skin bacterial infection * 1  1/286 (0.35%) 
Tinea pedis * 1  1/286 (0.35%) 
Tinea versicolour * 1  1/286 (0.35%) 
Tonsillitis * 1  1/286 (0.35%) 
Tooth abscess * 1  2/286 (0.70%) 
Tooth infection * 1  1/286 (0.35%) 
Tracheobronchitis * 1  2/286 (0.70%) 
Upper respiratory tract infection * 1  9/286 (3.15%) 
Upper respiratory tract infection bacterial * 1  1/286 (0.35%) 
Urethritis * 1  1/286 (0.35%) 
Urinary tract infection * 1  15/286 (5.24%) 
Urinary tract infection bacterial * 1  1/286 (0.35%) 
Vaginal infection * 1  1/286 (0.35%) 
Viral infection * 1  4/286 (1.40%) 
Vulvitis * 1  1/286 (0.35%) 
Vulvovaginal mycotic infection  1  3/286 (1.05%) 
Injury, poisoning and procedural complications   
Contusion * 1  2/286 (0.70%) 
Excoriation * 1  1/286 (0.35%) 
Fall * 1  1/286 (0.35%) 
Foot fracture * 1  2/286 (0.70%) 
Humerus fracture * 1  1/286 (0.35%) 
Joint sprain * 1  2/286 (0.70%) 
Lower limb fracture * 1  1/286 (0.35%) 
Meniscus lesion * 1  1/286 (0.35%) 
Nail injury * 1  1/286 (0.35%) 
Overdose * 1  8/286 (2.80%) 
Radius fracture * 1  1/286 (0.35%) 
Skeletal injury * 1  1/286 (0.35%) 
Tendon rupture * 1  1/286 (0.35%) 
Wound * 1  1/286 (0.35%) 
Wrist fracture * 1  1/286 (0.35%) 
Investigations   
Alanine aminotransferase increased * 1  24/286 (8.39%) 
Aspartate aminotransferase increased * 1  14/286 (4.90%) 
Basophil count increased * 1  1/286 (0.35%) 
Blood bilirubin increased * 1  4/286 (1.40%) 
Blood cholesterol increased * 1  5/286 (1.75%) 
Blood creatinine increased * 1  1/286 (0.35%) 
Blood lactate dehydrogenase increased * 1  2/286 (0.70%) 
Blood triglycerides increased * 1  2/286 (0.70%) 
Blood uric acid increased * 1  2/286 (0.70%) 
Body temperature increased * 1  2/286 (0.70%) 
Haematocrit increased * 1  1/286 (0.35%) 
Haemoglobin increased * 1  1/286 (0.35%) 
Hepatic enzyme increased * 1  2/286 (0.70%) 
Low density lipoprotein increased * 1  79/286 (27.62%) 
Lymphocyte count increased * 1  1/286 (0.35%) 
Neutrophil count decreased * 1  4/286 (1.40%) 
Transaminases increased * 1  2/286 (0.70%) 
Weight decreased * 1  1/286 (0.35%) 
Weight increased * 1  7/286 (2.45%) 
Metabolism and nutrition disorders   
Anorexia * 1  1/286 (0.35%) 
Hypercholesterolaemia * 1  5/286 (1.75%) 
Hyperglycaemia * 1  1/286 (0.35%) 
Hyperlipidaemia * 1  6/286 (2.10%) 
Hyperureicaemia * 1  1/286 (0.35%) 
Hypokalaemia  1  1/286 (0.35%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  8/286 (2.80%) 
Arthritis * 1  1/286 (0.35%) 
Back pain * 1  9/286 (3.15%) 
Bursitis * 1  2/286 (0.70%) 
Facit joint syndrome * 1  1/286 (0.35%) 
Groin pain * 1  1/286 (0.35%) 
Haemarthrosis * 1  1/286 (0.35%) 
Intervertebral disc protrusion * 1  1/286 (0.35%) 
Jaw cyst * 1  1/286 (0.35%) 
Joint range of motion decreased * 1  1/286 (0.35%) 
Ligament disorder * 1  1/286 (0.35%) 
Muscle spasms * 1  1/286 (0.35%) 
Muscle tightness * 1  2/286 (0.70%) 
Musculoskeletal chest pain * 1  1/286 (0.35%) 
Musculoskeletal pain * 1  2/286 (0.70%) 
Myalgia * 1  2/286 (0.70%) 
Osteoarthritis * 1  1/286 (0.35%) 
Osteoporosis * 1  1/286 (0.35%) 
Pain in extremity * 1  2/286 (0.70%) 
Rheumatoid arthritis * 1  25/286 (8.74%) 
Sacroiliitis * 1  1/286 (0.35%) 
Synovial cyst * 1  1/286 (0.35%) 
Tendonitis * 1  1/286 (0.35%) 
Tenosynovitis * 1  2/286 (0.70%) 
Tenosynovitis stenosans * 1  1/286 (0.35%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Benign bone neoplasm * 1  1/286 (0.35%) 
Bladder transitional cell carcinoma * 1  1/286 (0.35%) 
Non-Hodgkin's lymphoma * 1  1/286 (0.35%) 
Uterine leiomyoma * 1  1/286 (0.35%) 
Nervous system disorders   
Aphasia  1  1/286 (0.35%) 
Carpal tunnel syndrome * 1  1/286 (0.35%) 
Cervicobrachial syndrome * 1  1/286 (0.35%) 
Dizziness * 1  3/286 (1.05%) 
Dysaesthesia * 1  1/286 (0.35%) 
Dysgeusia * 1  1/286 (0.35%) 
Facial neuralgia * 1  1/286 (0.35%) 
Headache * 1  27/286 (9.44%) 
Migraine * 1  4/286 (1.40%) 
Multiple sclerosis relapse * 1  1/286 (0.35%) 
Paraesthesia  1  1/286 (0.35%) 
Restless legs syndrome * 1  2/286 (0.70%) 
Sciatica * 1  3/286 (1.05%) 
Somnolence * 1  1/286 (0.35%) 
Synope * 1  1/286 (0.35%) 
Tremor * 1  1/286 (0.35%) 
Pregnancy, puerperium and perinatal conditions   
Abortion * 1  1/286 (0.35%) 
Psychiatric disorders   
Depression * 1  2/286 (0.70%) 
Food aversion * 1  1/286 (0.35%) 
Insomnia * 1  2/286 (0.70%) 
Mood altered * 1  1/286 (0.35%) 
Post-traumatic stress disorder * 1  1/286 (0.35%) 
Sleep disorder * 1  3/286 (1.05%) 
Renal and urinary disorders   
Haematuria * 1  3/286 (1.05%) 
Leukocyturia * 1  2/286 (0.70%) 
Nocturia  1  1/286 (0.35%) 
Renal failure acute * 1  1/286 (0.35%) 
Urethral stenosis * 1  1/286 (0.35%) 
Reproductive system and breast disorders   
Breast disorder * 1  1/286 (0.35%) 
Breast pain * 1  1/286 (0.35%) 
Genital cyst * 1  1/286 (0.35%) 
Menopausal symptoms * 1  2/286 (0.70%) 
Vulvovaginal dryness * 1  1/286 (0.35%) 
Respiratory, thoracic and mediastinal disorders   
Allergic cough * 1  1/286 (0.35%) 
Asthma * 1  2/286 (0.70%) 
Cough  1  9/286 (3.15%) 
Dysphonia * 1  2/286 (0.70%) 
Dyspnoea * 1  3/286 (1.05%) 
Dyspnoea exertional * 1  1/286 (0.35%) 
Epistaxis  1  3/286 (1.05%) 
Interstitial lung disease * 1  1/286 (0.35%) 
Nasal dryness * 1  1/286 (0.35%) 
Nasal mucosal disorder * 1  1/286 (0.35%) 
Oropharyngeal blistering * 1  1/286 (0.35%) 
Oropharyngeal pain * 1  3/286 (1.05%) 
Pleurisy * 1  2/286 (0.70%) 
Rales * 1  1/286 (0.35%) 
Rhinitis allergic * 1  2/286 (0.70%) 
Rhinorrhoea * 1  1/286 (0.35%) 
Skin and subcutaneous tissue disorders   
Acne * 1  2/286 (0.70%) 
Alopecia  1  5/286 (1.75%) 
Blister * 1  1/286 (0.35%) 
Dermatitis allergic * 1  1/286 (0.35%) 
Drug eruption * 1  1/286 (0.35%) 
Dry skin * 1  1/286 (0.35%) 
Eczema * 1  8/286 (2.80%) 
Erythema * 1  1/286 (0.35%) 
Hyperhidrosis * 1  3/286 (1.05%) 
Pruritus * 1  7/286 (2.45%) 
Pruritus generalised * 1  1/286 (0.35%) 
Psoriasis * 1  2/286 (0.70%) 
Rash * 1  3/286 (1.05%) 
Rash macular * 1  1/286 (0.35%) 
Rash pruritic * 1  1/286 (0.35%) 
Skin chapped * 1  1/286 (0.35%) 
Skin exfoliation * 1  1/286 (0.35%) 
Skin fissures * 1  1/286 (0.35%) 
Skin irritation * 1  2/286 (0.70%) 
Skin reaction * 1  1/286 (0.35%) 
Skin ulcer * 1  1/286 (0.35%) 
Urticaria * 1  2/286 (0.70%) 
Vascular disorders   
Haematoma * 1  2/286 (0.70%) 
Hypertension * 1  16/286 (5.59%) 
Lymphoedema * 1  1/286 (0.35%) 
Thrombosis * 1  1/286 (0.35%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events.
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 after the first publication or presentation that involves the overall study. 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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann- LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00754559    
Other Study ID Numbers: ML21469
2008-000105-11
First Submitted: September 17, 2008
First Posted: September 18, 2008
Results First Submitted: April 7, 2014
Results First Posted: June 10, 2014
Last Update Posted: February 8, 2016