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A Long-term Extension Study of Tocilizumab (Myeloma Receptor Antibody [MRA]) in Patients With 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: NCT00721123
Recruitment Status : Completed
First Posted : July 23, 2008
Results First Posted : October 21, 2013
Last Update Posted : November 28, 2013
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 538
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tocilizumab 8 mg/kg
Hide Arm/Group Description Patients received tocilizumab (TCZ) 8 mg/kg intravenously every 4 weeks.
Period Title: Overall Study
Started 538
Completed 355
Not Completed 183
Reason Not Completed
Adverse Event             96
Death             10
Insufficient Therapeutic Response             21
Protocol Violation             1
Refused Treatment             41
Failure to Return             9
Withdrawal by Subject             5
Arm/Group Title Tocilizumab 8 mg/kg
Hide Arm/Group Description Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.
Overall Number of Baseline Participants 538
Hide Baseline Analysis Population Description
All-exposure population: All patients who entered the study and received at least one dose of tocilizumab at any time. Baseline was defined as the first dose of study drug, whether that occurred in the WA17822 study or the WA18695 study.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 538 participants
50.8  (12.03)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants
Female
443
  82.3%
Male
95
  17.7%
1.Primary Outcome
Title Adverse Event (AE) Summary Over Time
Hide Description The number of participants experiencing at least one adverse event (AE) is recorded for each 12-month time period, with multiple occurrences in a single individual counted. Because months were calculated as 28 days, the periods actually equate to 48 weeks.
Time Frame through 264 Weeks
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Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.
Arm/Group Title Months 0 - 12 Months 13 − 24 Months 25 - 36 Months 37 − 48 Months Greater Than 48
Hide Arm/Group Description:
Participants with scores during Months 0-12, which equates to baseline through Week 48.
Participants with scores during Months 13 − 24, which equates to Weeks 49-96.
Participants with scores during Months 25 - 36, which equates to Weeks 97-144.
Participants with scores during Months 37 − 48, which equates to Weeks 145-192.
Participants with scores during Months greater than 48, which equates to Weeks 193-264.
Overall Number of Participants Analyzed 538 509 463 434 414
Measure Type: Number
Unit of Measure: Participants
Experienced an adverse event 433 390 333 294 329
Experienced a serious adverse event 55 55 55 35 74
Experienced AE leading to withdrawal 24 17 22 8 32
2.Primary Outcome
Title Summary Adverse Event Rates Over Time
Hide Description

Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1. Patient year rates with confidence interval were calculated for adverse events of interest in evaluating the long-term safety of the product being studied.

Abbreviations include the following: adverse event (AE), adverse event of special interest (AESI), gastrointestinal (GI), serious adverse event (SAE), and investigational product (IP). Hypersensitivity events were defined as AEs that occurred during or within 24 hours of IP infusion and were not deemed "unrelated" to trial treatment by the investigator. This definition includes all types of AEs, regardless of whether or not they were consistent with hypersensitivity.

Medical confirmation of the AESI "GI perforation" was based on medical adjudication of events captured by the GI Perforation Standardised MedDRA Queries (SMQs).

Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.
Arm/Group Title Months 0 - 12 Months 13 − 24 Months 25 - 36 Months 37 − 48 Months Greater Than 48
Hide Arm/Group Description:
Participants with scores during Months 0-12, which equates to baseline through Week 48 (Total PY=486.34).
Participants with scores during Months 13 − 24, which equates to Weeks 49-96 (Total PY=444.49).
Participants with scores during Months 25 - 36, which equates to Weeks 97-144 (Total PY=410.93).
Participants with scores during Months 37 − 48, which equates to Weeks 145-192 (Total PY=388.25).
Participants with scores during Months greater than 48, which equates to Weeks 193-264 (Total PY=731.93).
Overall Number of Participants Analyzed 538 509 463 434 414
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Adverse Events per 100 Patient Years
Total AE rate
393.76
(376.32 to 411.80)
286.17
(270.66 to 302.34)
260.14
(244.78 to 276.22)
249.84
(234.36 to 266.07)
212.04
(201.62 to 222.86)
Total SAE rate
12.54
(9.59 to 16.11)
13.05
(9.91 to 16.87)
18.74
(14.79 to 23.42)
12.62
(9.34 to 16.69)
13.12
(10.62 to 16.02)
Rate for AEs leading to withdrawal
5.14
(3.33 to 7.59)
3.82
(2.23 to 6.12)
5.35
(3.36 to 8.11)
2.06
(0.89 to 4.06)
4.37
(2.99 to 6.17)
AESI All Infections
92.94
(84.57 to 101.92)
87.52
(79.03 to 96.66)
87.36
(78.56 to 96.88)
87.32
(78.27 to 97.12)
72.82
(66.77 to 79.27)
AESI Serious Infections
3.29
(1.88 to 5.34)
2.47
(1.24 to 4.43)
5.60
(3.55 to 8.40)
3.35
(1.78 to 5.73)
3.55
(2.32 to 5.20)
AESI Opportunistic infections
0 [1] 
(NA to NA)
0.22
(0.01 to 1.25)
0 [1] 
(NA to NA)
0.52
(0.06 to 1.86)
0.27
(0.03 to 0.99)
AESI Hypersensitivity events
27.35
(22.90 to 32.41)
9.90
(7.19 to 13.29)
5.35
(3.36 to 8.11)
3.86
(2.16 to 6.37)
4.10
(2.77 to 5.85)
AESI Hepatic events
0.41
(0.05 to 1.49)
0.90
(0.25 to 2.30)
0.49
(0.06 to 1.76)
1.03
(0.28 to 2.64)
0.68
(0.22 to 1.59)
AESI Myocardial infarction
0.62
(0.13 to 1.80)
0 [2] 
(NA to NA)
0.24
(0.01 to 1.36)
0.77
(0.16 to 2.26)
0.27
(0.03 to 0.99)
AESI Stroke, ischemic or hemorrhagic
0.21
(0.01 to 1.15)
0.22
(0.01 to 1.25)
0.73
(0.15 to 2.13)
0.26
(0.01 to 1.44)
0.41
(0.08 to 1.20)
AESI GI perforation
0 [3] 
(NA to NA)
0 [3] 
(NA to NA)
0.49
(0.06 to 1.76)
0.26
(0.01 to 1.44)
0 [3] 
(NA to NA)
AESI Malignancy
1.23
(0.45 to 2.69)
1.80
(0.78 to 3.55)
0.97
(0.27 to 2.49)
0.77
(0.16 to 2.26)
1.50
(0.75 to 2.69)
AESI Demyelinating disorders
0.21
(0.01 to 1.15)
0 [4] 
(NA to NA)
0 [4] 
(NA to NA)
0 [4] 
(NA to NA)
0 [4] 
(NA to NA)
AESI Serious bleeding disorders
0.62
(0.13 to 1.80)
0.45
(0.05 to 1.63)
0.49
(0.06 to 1.76)
0.26
(0.01 to 1.44)
0.68
(0.22 to 1.59)
[1]
There were no opportunistic infections in this period.
[2]
There were no myocardial infarctions in this period.
[3]
There were no medically confirmed GI perforations in this period.
[4]
There were no demyelinating disorders in this period.
3.Primary Outcome
Title Overall Death Rate Over Time
Hide Description

Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1.

To calculate the death rate, the total cumulative number of years that all participants were exposed to the drug, from first active drug intake to last safety assessment available + 1, was calculated as 2461.94. Since 10 participants died during that time, the death rate per year was not informative (0.00). Therefore, the overall death rate was calculated with the confidence interval based on events per 100 patient years exposure.

Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which included all participants who entered the study and received at least one dose of tocilizumab at any time.
Arm/Group Title Tocilizumab 8 mg/kg
Hide Arm/Group Description:
Patients received tocilizumab (TCZ) 8 mg/kg intravenously every 4 weeks.
Overall Number of Participants Analyzed 538
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Deaths per 100 PY
0.41
(0.19 to 0.75)
4.Secondary Outcome
Title Participants Showing Improvement in Rheumatoid Arthritis Symptoms Over Time, Through 264 Weeks
Hide Description

The American College of Rheumatology (ACR) established certain criteria to measure improvement in rheumatoid arthritis symptoms that include tender or swollen joint counts and five other criteria, including acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire.

Clinical trials use the ACR Score, based on those criteria, as a standard for reporting different degrees of improvement in rheumatoid arthritis symptoms.

Scores on the ACR scale may be up to ACR100 because the number after "ACR" is the percent of improvement in tender or swollen joint counts as well as in three of the other five criteria. Clinical trials determine the percentage of participants who achieve that score - that percentage of improvement.

Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 522 480 422 413 387 367
Measure Type: Number
Unit of Measure: Percentage of Participants
ACR20 63.2 76.0 81.2 83.3 82.2 83.9
ACR50 41.2 50.6 58.1 59.6 62.5 67.8
ACR70 17.4 27.1 38.2 41.9 42.1 45.8
ACR90 4.8 5.2 11.3 15.3 16.8 19.3
5.Secondary Outcome
Title Percentage of Participants Classified as Responders by Disease Activity Scores Over Time, Through 264 Weeks
Hide Description The disease activity score 28 (DAS28) is a combined index for measuring disease activity in rheumatic arthritis (RA) that includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The DAS28 scale ranges from 0 to 10, where lower scores represent less disease activity. Participants with DAS28 scores less than 2.6 were categorized as responders with remission and those with DAS 28 scores of 3.2 or less were categorized as responders with low disease activity (LDA). The percentage of participants classified as responders in each category was recorded over time.
Time Frame through 264 Weeks
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Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 516 470 430 410 381 363
Measure Type: Number
Unit of Measure: Percentage of Participants
Responders with Remission (DAS<2.6) 24.6 43.0 53.7 54.9 57.2 60.6
Responders with Low Disease Activity (DAS</= 3.2) 41.7 57.7 67.0 71.2 70.6 72.2
6.Secondary Outcome
Title Percentage of Participants Classified as Responders by EULAR Response Over Time, Through 264 Weeks
Hide Description Participants were classified as responders based on a European League Against Rheumatism (EULAR) response of Good or Moderate. Comparing the DAS28 from one patient on two different time points, it is possible to define improvement or response. The EULAR response criteria take into consideration both the first score and the change in score in order to classify them as good response, moderate response or no response. The percentage of participants who were classified as responders was recorded, as posted below.
Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 514 468 429 409 380 362
Measure Type: Number
Unit of Measure: Percentage of Participants
EULAR Good Response 41.2 56.6 65.5 70.9 69.5 71.0
EULAR Moderate Response 48.1 39.1 29.8 25.9 26.8 25.1
7.Secondary Outcome
Title Change From Baseline in Scores for Swollen and Tender Joint Counts Over Time, Through 264 Weeks
Hide Description

Swollen joint count (SJC) includes an assessment of 66 joints, and tender joint count (TJC) include an assessment of 68 joints. Joint prosthesis, arthrodesis or fused joints were not considered. Joints were assessed and classified as swollen/not swollen, and tender/not tender, by pressure and joint manipulation on physical examination. Change from Baseline in the SJC and TJC were calculated at given time points, and a negative change indicates improvement.

A small proportion of participants in the all-exposure population reduced or stopped their oral corticosteroid use due to sustained efficacy (defined as at least a 50% improvement in both swollen joint count (SJC) and tender joint count (TJC).

Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 532 506 454 422 405 371
Mean (Standard Deviation)
Unit of Measure: Joints
Swollen Joint Count (SJC) -11.7  (11.50) -13.6  (11.04) -15.6  (11.51) -16.2  (11.46) -16.2  (11.48) -16.5  (11.26)
Tender Joint Count (TJC) -17.4  (14.82) -20.3  (15.12) -23.1  (15.82) -23.8  (16.14) -23.8  (15.89) -24.8  (16.37)
8.Secondary Outcome
Title Change From Baseline in Scores for Health Assessment Questionnaire − Disability Index Over Time, Through 264 Weeks
Hide Description

The Stanford Health Assessment Questionnaire - Disability Index (HAQ-DI) is a questionnaire specific for rheumatoid arthritis with 8 component sets (domains): dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has 2-3 questions (for a total of 20) that participants answer with categorical answers enumerated as a scale of 0-3, where 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do.

To calculate the HAQ-DI the patient must have a domain score for at least 6 of the eight domains. The HAQ-DI is the sum of the domain scores, divided by the number of domains that have a score (in range 6-8). The resulting HAQ-DI scores are on a scale that ranges from 0 to 3, where 0=lowest level of difficulty and 3=highest level of difficulty. A negative change from baseline indicates improvement.

Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 445 408 376 349 332 316
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-0.49  (0.582) -0.53  (0.614) -0.59  (0.636) -0.61  (0.655) -0.65  (0.661) -0.62  (0.693)
9.Secondary Outcome
Title Change From Baseline in Scores for Patient's Global Assessment of Disease Activity Over Time, Through 264 Weeks
Hide Description Patient's global assessment of disease activity is the patient's overall assessment of their disease activity during specified time periods on a 100 mm horizontal visual analogue scale (VAS). The left-hand extreme of the line was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme as "maximum disease activity" (maximum arthritis disease activity). Change from baseline was calculated for given periods, and a negative change indicates improvement.
Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 521 479 442 414 387 367
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-26.6  (26.87) -30.3  (27.71) -31.1  (27.65) -31.6  (26.74) -33.0  (26.83) -32.9  (27.58)
10.Secondary Outcome
Title Change From Baseline in Scores for Physician's Global Assessment of Disease Activity Over Time, Through 264 Weeks
Hide Description Physician's global assessment of disease activity is the treating physician's assessment of the patient's current disease activity on a 100 mm horizontal visual analogue scale (VAS). The extreme left end of the line was described as "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end as "maximum disease activity". Change from baseline was calculated for given periods, and a negative change indicates improvement.
Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 521 479 439 416 389 369
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-33.8  (23.33) -38.1  (23.77) -41.1  (23.79) -43.2  (23.26) -44.8  (22.66) -44.4  (23.64)
11.Secondary Outcome
Title Change From Baseline in Scores for Patient's Level of Pain Over Time, Through 264 Weeks
Hide Description The patient's assessment of the patient's current level of pain on a 100 mm horizontal VAS was recorded. The extreme left end of the line was described as "no pain" and the extreme right end as "unbearable pain". Change from baseline was calculated for given periods, and a negative change indicates improvement.
Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 521 479 442 414 388 367
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-23.7  (26.38) -26.7  (27.27) -28.0  (26.33) -28.1  (25.99) -29.5  (26.98) -29.2  (26.84)
12.Secondary Outcome
Title Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Measure for Fatigue Over Time, Through 264 Weeks
Hide Description

Quality of life is measured using the sub-scale for Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). The assessment was originally developed for chronic illnesses and is now widely used for patients with rheumatoid arthritis.

FACIT-F is a 13-item questionnaire. Participants score each item on a 5-point scale: 0 (Not at all) to 4 (Very much), for a highest possible score of 52. The responses are transformed into a FACIT-F score, where a higher score reflects an improvement. The percentage of participants with at least a 5-point improvement from baseline in the Facit-F score is shown at categorical time points.

Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 523 482 444 414 390 370
Measure Type: Number
Unit of Measure: Percentage of Participants
66.0 58.7 61.5 62.3 60.0 62.2
13.Secondary Outcome
Title Percentage of Participants With at Least a 5-point Improvement From Baseline in Quality of Life Using the 36-Item Short-Form Health Survey (SF-36) Over Time, Through 264 Weeks
Hide Description The SF-36 Health Survey is a standardized questionnaire consisting of 36 questions that measures patient-reported symptoms on 8 dimensions; it is used to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL. The percentage of participants with at least a 5-point improvement from baseline is presented for each subscale.
Time Frame through 264 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time, with a score at the given time point.
Arm/Group Title Week 24 Week 48 Week 108 Week 156 Week 204 Week 264
Hide Arm/Group Description:
Participants with scores at 24 weeks post-baseline.
Participants with scores at 48 weeks post-baseline.
Participants with scores at 108 weeks post-baseline.
Participants with scores at 156 weeks post-baseline.
Participants with scores at 204 weeks post-baseline.
Participants with scores at 264 weeks post-baseline.
Overall Number of Participants Analyzed 423 424 395 373 344 334
Measure Type: Number
Unit of Measure: Percentage of Participants
SF-36 MCS 48.2 46.2 48.6 49.9 49.7 49.1
SF-36 PCS 63.8 69.1 71.1 71.3 73.3 71.3
Time Frame [Not Specified]
Adverse Event Reporting Description All-exposure population: All patients who entered the study and received at least 1 dose of tocilizumab at any time.
 
Arm/Group Title Tocilizumab 8 mg/kg
Hide Arm/Group Description Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.
All-Cause Mortality
Tocilizumab 8 mg/kg
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Tocilizumab 8 mg/kg
Affected / at Risk (%)
Total   199/538 (36.99%) 
Blood and lymphatic system disorders   
Anaemia  1  2/538 (0.37%) 
Anaemia of chronic disease  1  1/538 (0.19%) 
Iron deficiency anaemia  1  1/538 (0.19%) 
Cardiac disorders   
Acute myocardial infarction  1  3/538 (0.56%) 
Atrial fibrillation  1  3/538 (0.56%) 
Acute coronary syndrome  1  2/538 (0.37%) 
Angina unstable  1  2/538 (0.37%) 
Coronary artery disease  1  2/538 (0.37%) 
Myocardial infarction  1  2/538 (0.37%) 
Supraventricular tachycardia  1  2/538 (0.37%) 
Arteriosclerosis coronary artery  1  1/538 (0.19%) 
Atrioventricular block complete  1  1/538 (0.19%) 
Cardiac failure  1  1/538 (0.19%) 
Cardiac failure congestive  1  1/538 (0.19%) 
Cardio-respiratory arrest  1  1/538 (0.19%) 
Dressler's syndrome  1  1/538 (0.19%) 
Supraventricular extrasystoles  1  1/538 (0.19%) 
Tachyarrhythmia  1  1/538 (0.19%) 
Ear and labyrinth disorders   
Sudden hearing loss  1  1/538 (0.19%) 
Vertigo  1  1/538 (0.19%) 
Endocrine disorders   
Goitre  1  1/538 (0.19%) 
Eye disorders   
Cataract  1  2/538 (0.37%) 
Ulcerative keratitis  1  1/538 (0.19%) 
Gastrointestinal disorders   
Inguinal hernia  1  4/538 (0.74%) 
Gastritis  1  3/538 (0.56%) 
Abdominal pain upper  1  1/538 (0.19%) 
Diarrhoea  1  2/538 (0.37%) 
Diverticular perforation  1  2/538 (0.37%) 
Pancreatitis  1  2/538 (0.37%) 
Abdominal pain  1  1/538 (0.19%) 
Anal fistula  1  1/538 (0.19%) 
Constipation  1  1/538 (0.19%) 
Crohn's disease  1  1/538 (0.19%) 
Flatulence  1  1/538 (0.19%) 
Gastrointestinal haemorrhage  1  1/538 (0.19%) 
Gastrooesophageal reflux disease  1  1/538 (0.19%) 
Glossitis  1  1/538 (0.19%) 
Haemorrhoidal haemorrhage  1  1/538 (0.19%) 
Large intestinal ulcer  1  1/538 (0.19%) 
Melaena  1  1/538 (0.19%) 
Oesophageal perforation  1  1/538 (0.19%) 
Pancreatitis acute  1  1/538 (0.19%) 
Rectal haemorrhage  1  1/538 (0.19%) 
Umbilical hernia  1  1/538 (0.19%) 
General disorders   
Device breakage  1  2/538 (0.37%) 
Device dislocation  1  2/538 (0.37%) 
Non-cardiac chest pain  1  2/538 (0.37%) 
Chest pain  1  1/538 (0.19%) 
Hepatobiliary disorders   
Cholecystitis  1  4/538 (0.74%) 
Cholelithiasis  1  4/538 (0.74%) 
Cholecystitis acute  1  2/538 (0.37%) 
Cholecystitis chronic  1  1/538 (0.19%) 
Perforation bile duct  1  1/538 (0.19%) 
Immune system disorders   
Allergy to arthropod bite  1  1/538 (0.19%) 
Anaphylactic reaction  1  1/538 (0.19%) 
Sarcoidosis  1  1/538 (0.19%) 
Infections and infestations   
Pneumonia  1  12/538 (2.23%) 
Diverticulitis  1  5/538 (0.93%) 
Cellulitis  1  4/538 (0.74%) 
Erysipelas  1  4/538 (0.74%) 
Gastroenteritis  1  4/538 (0.74%) 
Abscess limb  1  3/538 (0.56%) 
Bronchopneumonia  1  3/538 (0.56%) 
Sepsis  1  3/538 (0.56%) 
Urinary tract infection  1  3/538 (0.56%) 
Cellulitis staphylococcal  1  2/538 (0.37%) 
Herpes zoster  1  2/538 (0.37%) 
Pneumonia pneumococcal  1  2/538 (0.37%) 
Postoperative wound infection  1  2/538 (0.37%) 
Pulmonary tuberculosis  1  2/538 (0.37%) 
Respiratory tract infection  1  2/538 (0.37%) 
Sinusitis  1  2/538 (0.37%) 
Subcutaneous abscess  1  2/538 (0.37%) 
Varicella  1  2/538 (0.37%) 
Abscess neck  1  1/538 (0.19%) 
Appendicitis  1  1/538 (0.19%) 
Arthritis bacterial  1  1/538 (0.19%) 
Bronchitis  1  1/538 (0.19%) 
Bursitis infective staphylococcal  1  1/538 (0.19%) 
Douglas' abscess  1  1/538 (0.19%) 
Endocarditis staphylococcal  1  1/538 (0.19%) 
Gastrointestinal infection  1  1/538 (0.19%) 
Helicobacter gastritis  1  1/538 (0.19%) 
Intervertebral discitis  1  1/538 (0.19%) 
Lobar pneumonia  1  1/538 (0.19%) 
Lung Abscess  1  1/538 (0.19%) 
Mediastinitis  1  1/538 (0.19%) 
Osteomyelitis  1  1/538 (0.19%) 
Peritonitis  1  1/538 (0.19%) 
Peritonsillar abscess  1  1/538 (0.19%) 
Post procedural infection  1  1/538 (0.19%) 
Proteus infection  1  1/538 (0.19%) 
Pulmonary sepsis  1  1/538 (0.19%) 
Pyelonephritis acute  1  1/538 (0.19%) 
Septic arthritis  1  1/538 (0.19%) 
Staphylococcal septic shock  1  1/538 (0.19%) 
Soft tissue infection  1  1/538 (0.19%) 
Tuberculosis  1  1/538 (0.19%) 
Tuberculous pleurisy  1  1/538 (0.19%) 
Upper respiratory tract infection  1  1/538 (0.19%) 
Wound infection  1  1/538 (0.19%) 
Injury, poisoning and procedural complications   
Femoral neck fracture  1  2/538 (0.37%) 
Femur fracture  1  2/538 (0.37%) 
Post procedural haemorrhage  1  2/538 (0.37%) 
Ankle fracture  1  1/538 (0.19%) 
Carbon monoxide poisoning  1  1/538 (0.19%) 
Contusion  1  1/538 (0.19%) 
Dislocation of vertebra  1  1/538 (0.19%) 
Fractured ischium  1  1/538 (0.19%) 
Gas poisoning  1  1/538 (0.19%) 
Hand fracture  1  1/538 (0.19%) 
Hip fracture  1  1/538 (0.19%) 
Incision site haematoma  1  1/538 (0.19%) 
Joint injury  1  1/538 (0.19%) 
Laceration  1  1/538 (0.19%) 
Lower limb fracture  1  1/538 (0.19%) 
Meniscus lesion  1  1/538 (0.19%) 
Overdose  1  1/538 (0.19%) 
Periprosthetic fracture  1  1/538 (0.19%) 
Post procedural complication  1  1/538 (0.19%) 
Postoperative fever  1  1/538 (0.19%) 
Radius fracture  1  1/538 (0.19%) 
Tendon rupture  1  1/538 (0.19%) 
Tibia fracture  1  1/538 (0.19%) 
Upper limb fracture  1  1/538 (0.19%) 
Vascular bypass dysfunction  1  1/538 (0.19%) 
Wound dehiscence  1  1/538 (0.19%) 
Wrist fracture  1  1/538 (0.19%) 
Metabolism and nutrition disorders   
Hypokalaemia  1  1/538 (0.19%) 
Musculoskeletal and connective tissue disorders   
Osteoarthritis  1  6/538 (1.12%) 
Back pain  1  3/538 (0.56%) 
Intervertebral disc protrusion  1  3/538 (0.56%) 
Osteoporotic fracture  1  2/538 (0.37%) 
Foot deformity  1  1/538 (0.19%) 
Haemarthrosis  1  1/538 (0.19%) 
Lumbar spinal stenosis  1  1/538 (0.19%) 
Lupus-like syndrome  1  1/538 (0.19%) 
Muscle necrosis  1  1/538 (0.19%) 
Muscular weakness  1  1/538 (0.19%) 
Musculoskeletal chest pain  1  1/538 (0.19%) 
Osteonecrosis  1  1/538 (0.19%) 
Pain in extremity  1  1/538 (0.19%) 
Rheumatoid arthritis  1  1/538 (0.19%) 
Spinal osteoarthritis  1  1/538 (0.19%) 
Spondylolisthesis  1  1/538 (0.19%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer  1  3/538 (0.56%) 
Squamous cell carcinoma of the cervix  1  3/538 (0.56%) 
Breast cancer in situ  1  2/538 (0.37%) 
Basal cell carcinoma  1  1/538 (0.19%) 
Breast cancer stage II  1  1/538 (0.19%) 
Breast cancer stage III  1  1/538 (0.19%) 
Colon cancer metastatic  1  1/538 (0.19%) 
Colon cancer stage II  1  1/538 (0.19%) 
Diffuse large B-cell lymphoma stage III  1  1/538 (0.19%) 
Endometrial cancer  1  1/538 (0.19%) 
Haemangioma  1  1/538 (0.19%) 
Hepatic neoplasm malignant  1  1/538 (0.19%) 
Laryngeal cancer metastatic  1  1/538 (0.19%) 
Lipoma  1  1/538 (0.19%) 
Lung adenocarcinoma  1  1/538 (0.19%) 
Lung adenocarcinoma stage III  1  1/538 (0.19%) 
Malignant pleural effusion  1  1/538 (0.19%) 
Metastatic gastric cancer  1  1/538 (0.19%) 
Metastatic squamous cell carcinoma  1  1/538 (0.19%) 
Ovarian cancer metastatic  1  1/538 (0.19%) 
Ovarian epithelial cancer  1  1/538 (0.19%) 
Prostate cancer stage I  1  1/538 (0.19%) 
Rectal cancer stage III  1  1/538 (0.19%) 
Skin papilloma  1  1/538 (0.19%) 
Small cell lung cancer state unspecified  1  1/538 (0.19%) 
Thyroid adenoma  1  1/538 (0.19%) 
Uterine leiomyoma  1  1/538 (0.19%) 
Nervous system disorders   
Sciatica  1  3/538 (0.56%) 
Carpal tunnel syndrome  1  1/538 (0.19%) 
Cerebral ischaemia  1  1/538 (0.19%) 
Dyskinesia  1  1/538 (0.19%) 
Essential tremor  1  1/538 (0.19%) 
Haemorrhagic stroke  1  1/538 (0.19%) 
Headache  1  1/538 (0.19%) 
Hypertensive encephalopathy  1  1/538 (0.19%) 
Hypoaesthesia  1  1/538 (0.19%) 
Migraine  1  1/538 (0.19%) 
Nerve root compression  1  1/538 (0.19%) 
Presyncope  1  1/538 (0.19%) 
Syncope  1  1/538 (0.19%) 
Thrombotic cerebral infarction  1  1/538 (0.19%) 
Tremor  1  1/538 (0.19%) 
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous  1  3/538 (0.56%) 
Pregnancy  1  3/538 (0.56%) 
Psychiatric disorders   
Confusional state  1  2/538 (0.37%) 
Adjustment disorder  1  1/538 (0.19%) 
Anxiety  1  1/538 (0.19%) 
Delirium  1  1/538 (0.19%) 
Major depression  1  1/538 (0.19%) 
Schizophrenia  1  1/538 (0.19%) 
Suicide attempt  1  1/538 (0.19%) 
Renal and urinary disorders   
Calculus urinary  1  1/538 (0.19%) 
Nephrolithiasis  1  1/538 (0.19%) 
Renal colic  1  1/538 (0.19%) 
Urinary incontinence  1  1/538 (0.19%) 
Reproductive system and breast disorders   
Ovarian cyst  1  2/538 (0.37%) 
Uterine haemorrhage  1  2/538 (0.37%) 
Endometriosis  1  1/538 (0.19%) 
Female genital tract fistula  1  1/538 (0.19%) 
Uterine polyp  1  1/538 (0.19%) 
Uterine prolapse  1  1/538 (0.19%) 
Respiratory, thoracic and mediastinal disorders   
Interstitial lung disease  1  2/538 (0.37%) 
Pulmonary embolism  1  2/538 (0.37%) 
Acute respiratory failure  1  1/538 (0.19%) 
Emphysema  1  1/538 (0.19%) 
Mediastinal haemorrhage  1  1/538 (0.19%) 
Pleural effusion  1  1/538 (0.19%) 
Pneumonitis  1  1/538 (0.19%) 
Rheumatoid lung  1  1/538 (0.19%) 
Skin and subcutaneous tissue disorders   
Actinic keratosis  1  1/538 (0.19%) 
Angioedema  1  1/538 (0.19%) 
Cutaneous vasculitis  1  1/538 (0.19%) 
Erythema  1  1/538 (0.19%) 
Hyperkeratosis  1  1/538 (0.19%) 
Vascular disorders   
Hypertension  1  3/538 (0.56%) 
Vericose vein  1  2/538 (0.37%) 
Deep vein thrombosis  1  1/538 (0.19%) 
Hypertensive crisis  1  1/538 (0.19%) 
Iliac artery occlusion  1  1/538 (0.19%) 
Orthostatic hypotension  1  1/538 (0.19%) 
Peripheral arterial occlusive disease  1  1/538 (0.19%) 
Vasculitis necrotising  1  1/538 (0.19%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tocilizumab 8 mg/kg
Affected / at Risk (%)
Total   475/538 (88.29%) 
Blood and lymphatic system disorders   
Leukopenia  1  31/538 (5.76%) 
Ear and labyrinth disorders   
Vertigo  1  27/538 (5.02%) 
Eye disorders   
Conjunctivitis  1  27/538 (5.02%) 
Gastrointestinal disorders   
Diarrhoea  1  85/538 (15.80%) 
Dyspepsia  1  85/538 (15.80%) 
Nausea  1  50/538 (9.29%) 
Gastritis  1  35/538 (6.51%) 
Abdominal pain  1  32/538 (5.95%) 
Abdominal pain upper  1  32/538 (5.95%) 
Mouth ulceration  1  29/538 (5.39%) 
Gastrooesophageal reflux disease  1  28/538 (5.20%) 
Infections and infestations   
Upper respiratory tract infection  1  136/538 (25.28%) 
Nasopharyngitis  1  133/538 (24.72%) 
Urinary tract infection  1  93/538 (17.29%) 
Bronchitis  1  83/538 (15.43%) 
Gastroenteritis  1  69/538 (12.83%) 
Pharyngitis  1  60/538 (11.15%) 
Influenza  1  43/538 (7.99%) 
Oral herpes  1  37/538 (6.88%) 
Sinusitis  1  32/538 (5.95%) 
Rhinitis  1  31/538 (5.76%) 
Investigations   
Alanine aminotransferase increased  1  59/538 (10.97%) 
Transaminases increased  1  51/538 (9.48%) 
Metabolism and nutrition disorders   
Hypercholesterolaemia  1  33/538 (6.13%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  64/538 (11.90%) 
Rheumatoid arthritis  1  64/538 (11.90%) 
Arthralgia  1  37/538 (6.88%) 
Nervous system disorders   
Headache  1  89/538 (16.54%) 
Dizziness  1  35/538 (6.51%) 
Psychiatric disorders   
Depression  1  43/538 (7.99%) 
Insomnia  1  30/538 (5.58%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  46/538 (8.55%) 
Oropharyngeal pain  1  32/538 (5.95%) 
Skin and subcutaneous tissue disorders   
Rash  1  30/538 (5.58%) 
Vascular disorders   
Hypertension  1  107/538 (19.89%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00721123    
Other Study ID Numbers: WA18695
First Submitted: July 22, 2008
First Posted: July 23, 2008
Results First Submitted: July 17, 2013
Results First Posted: October 21, 2013
Last Update Posted: November 28, 2013