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An Observational Study on RoActemra/Actemra (Tocilizumab) in Clinical Practice in Patients With Rheumatoid Arthritis (TRUST)

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ClinicalTrials.gov Identifier: NCT01394276
Recruitment Status : Completed
First Posted : July 14, 2011
Results First Posted : June 7, 2016
Last Update Posted : June 7, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Rheumatoid Arthritis
Enrollment 322
Recruitment Details A total of 322 participants were enrolled across 59 study centers in Italy from 31 May 2011 to 24 April 2013.
Pre-assignment Details  
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants with moderate to severe Rheumatoid arthritis (RA) who had received RoActemra [Tocilizumab (TCZ)] treatment for 6 months prior to initiation of study and are inadequate responders to Disease Modifying Anti-Rheumatic Drugs (DMARDs) and anti-Tumor Necrosis Factors (anti-TNFs) agents were observed. Participants received treatment with TCZ with dose of 8 milligrams per kilogram (mg/kg) body weight, intravenously once every 4 weeks for 12 months according to European Union (EU) approved dosage, and Summary of Product Characteristics (SmPC).
Period Title: Overall Study
Started 322
Completed 260
Not Completed 62
Reason Not Completed
Related Adverse event (AEs)             15
Not related AEs             9
Remission of disease             2
Insufficient therapeutic effect             17
Insufficient compliance             9
Lost to Follow-up             5
Participant moved to another site             1
Pregnancy             1
unavailability of drug at the Hospital             2
Symptoms of concurrent diseases             1
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Baseline Participants 322
Hide Baseline Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 322 participants
55.8  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 322 participants
Female
260
  80.7%
Male
62
  19.3%
1.Primary Outcome
Title Percentage of Participants Achieving Low Disease Activity After 6 Months of Treatment
Hide Description Low disease activity is defined as a disease activity score based on 28 joint count (DAS28) score lesser or equal to (</=) 3.2. The DAS28 is an evaluation index of RA. DAS28 applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints), 3. Erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) measurement, 4. Participant’s judgement on his own overall health status expressed by a visual analogue scale (VAS). The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control, higher scores represent higher disease activity and negative change from baseline score indicates improvement. Percentage of participants with low disease activity was reported.
Time Frame Up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. Data allowing the evaluation of low disease activity was available for 226 participants in TCZ group.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 226
Measure Type: Number
Unit of Measure: percentage of participants
57.52
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0237
Comments [Not Specified]
Method Exact binomial proportion test
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Achieving Disease Remission After 6 Months of Treatment
Hide Description Disease remission is defined as a DAS28 score < 2.6. The DAS28 is an evaluation index of RA. DAS28 applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints), 3. ESR or CRP measurement, 4. Participant’s judgment on his own overall health status expressed by a VAS and calculates total score of 0 to approximately 10. The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control, higher scores represent higher disease activity and negative change from baseline score indicates improvement. The response to therapy is defined according to the disease activity detected, compared to the previous clinical evaluation. Percentage of participants with disease remission was reported.
Time Frame Up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. Data allowing the evaluation of disease remission was available for 226 participants in TCZ group.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 226
Measure Type: Number
Unit of Measure: percentage of participants
38.05
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Exact binomial proportion test
Comments [Not Specified]
3.Secondary Outcome
Title Mean Score of Disease Activity Based on 28 Joint Count in Participants on Monotherapy With Tocilizumab
Hide Description The DAS28 is an evaluation index of RA. DAS28 applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints), 3.ESR or CRP measurement, 4. Participant’s judgment on his own overall health status expressed by a VAS and calculates total score of 0 to approximately 10. The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control, higher scores represent higher disease activity and negative change from baseline score indicates improvement. The response to therapy is defined according to the disease activity detected, compared to the previous clinical evaluation.
Time Frame Baseline (Month 0), Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. Data allowing the evaluation of disease activity based on 28 joints count was available for 93 participants in TCZ group.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; n = 93 5.4  (1.3)
Month 1; n = 60 3.6  (1.3)
Month 2; n = 63 3.3  (1.1)
Month 4; n = 64 3.2  (1.3)
Month 6; n = 75 3.0  (1.2)
Month 12; n = 61 2.8  (1.2)
4.Secondary Outcome
Title Mean Score of Fatigue Based on Visual Analogue Scale in Participants on Monotherapy With Tocilizumab
Hide Description VAS for fatigue is a 100 mm scale for participant’s assessment of their current level of fatigue. The ‘0 ‘mm corresponds to “no perception of fatigue,” ‘100 mm’ is the “maximum level of fatigue that may be perceived.” Mean score of VAS fatigue in participants were reported.
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. Data allowing the evaluation of fatigue based on VAS was available for 50 participants in TCZ group. The “n” represents the number of participants analyzed at a specified time point.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; n = 50 62.8  (23.2)
Month 1; n = 39 48.2  (27.9)
Month 2; n = 36 41.8  (25.6)
Month 4; n = 39 38.8  (26.6)
Month 6; n = 48 38.8  (26.1)
Month 12; n = 46 33.1  (24.9)
5.Secondary Outcome
Title Mean Score of Health Assessment Questionnaire in Participants on Monotherapy With Tocilizumab
Hide Description The health assessment questionnaire (HAQ) is a participant-completed questionnaire specific for RA, recommended by the American college of Rheumatology for the evaluation of quality of life. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. There are 4 possible responses for each question: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do. To calculate HAQ, the participant must have a component set score for at least 6 of 8 component set. The HAQ is the sum of the scores, divided by the number of component set that have a score (in range 6-8) for a total possible score of minimum/maximum i.e., 0 (best) to 3 (worst).
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. Data allowing the evaluation of HAQ was available for 66 participants in TCZ group. The “n” represents the number of participants analyzed at a specified time point.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 66
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; n = 66 1.6  (0.8)
Month 1; n = 50 1.2  (0.7)
Month 2; n = 55 1.1  (0.8)
Month 4; n = 54 1.0  (0.9)
Month 6; n = 59 1.1  (0.8)
Month 12; n = 50 1.1  (0.8)
6.Secondary Outcome
Title Number of Participants With Concomitant Medications
Hide Description Number of participants treated with at least one concomitant medication i.e., corticosteroid (Prednisone, Methyl prednisolone) was reported.
Time Frame Up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: participants
Prednisone 142
Methylprednisolone 130
7.Secondary Outcome
Title Percentage of Participants Discontinuing Treatment With Tocilizumab
Hide Description The percentage of participants who prematurely discontinued treatment with TCZ during the study period was reported.
Time Frame Up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: percentage of participants
19.2
8.Secondary Outcome
Title Number of Participants With Any Adverse Events and Serious Adverse Events
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a participant who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time Frame Up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: participants
Any AE 214
Any SAE 28
9.Secondary Outcome
Title Percentage of Participants Still on Tocilizumab Treatment Till 12 Months After the 1st Infusion
Hide Description Percentage of participants who continued treatment till 12 months after the first infusion with TCZ was reported.
Time Frame Up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: percentage of participants
80.8
10.Secondary Outcome
Title Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Second Metacarpo-phalangeal Joint of Right Hand.
Hide Description The presence and severity of synovial hyperplasia (SH) and joint effusion (JE) of second metacarpo-phalangeal (MCP) joint of right hand was determined by ultrasound examination. According to the method proposed by Naredo, synovial hyperplasia and joint effusion were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intra articular surface).
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: participants
SH Absent, Baseline 25
SH Mild, Baseline 7
SH Moderate, Baseline 16
SH Marked, Baseline 5
SH Absent, Month 1 1
SH Mild, Month 1 1
SH Moderate, Month 1 3
SH Marked, Month 1 1
SH Absent, Month 2 2
SH, Mild, Month 2 3
SH Moderate, Month 2 6
SH Marked, Month 2 0
SH Absent, Month 4 2
SH Mild, Month 4 4
SH Moderate, Month 4 3
SH Marked, Month 4 0
SH Absent, Month 6 4
SH Mild, Month 6 5
SH Moderate, Month 6 4
SH Marked, Month 6 0
SH Absent, Month 12 4
SH Mild, Month 12 6
SH Moderate, Month 12 3
SH Marked, Month 12 0
JE Absent, Baseline 23
JE Mild, Baseline 9
JE Moderate, Baseline 17
JE Marked, Baseline 6
JE Absent, Month 1 1
JE Mild, Month 1 1
JE Moderate, Month 1 3
JE Marked, Month 1 1
JE Absent, Month 2 4
JE Mild, Month 2 6
JE Moderate, Month 2 1
JE Marked, Month 2 0
JE Absent, Month 4 3
JE Mild, Month 4 5
JE Moderate, Month 4 2
JE Marked, Month 4 0
JE Absent, Month 6 7
JE Mild, Month 6 5
JE Moderate, Month 6 1
JE Marked, Month 6 0
JE Absent, Month 12 7
JE Mild, Month 12 6
JE Moderate, Month 12 0
JE Marked, Month 12 0
Vascularization, Absent, Baseline 26
Vascularization, Mild, Baseline 8
Vascularization, Moderate, Baseline 8
Vascularization, Marked, Baseline 11
Vascularization, Absent, Month 1 2
Vascularization, Mild, Month 1 1
Vascularization, Moderate, Month 1 2
Vascularization, Marked, Month 1 1
Vascularization, Absent, Month 2 4
Vascularization, Mild, Month 2 7
Vascularization, Moderate, Month 2 0
Vascularization, Marked, Month 2 0
Vascularization, Absent, Month 4 2
Vascularization, Mild, Month 4 4
Vascularization, Moderate, Month 4 2
Vascularization, Marked, Month 4 0
Vascularization, Absent, Month 6 6
Vascularization, Mild, Month 6 3
Vascularization, Moderate, Month 6 2
Vascularization, Marked, Month 6 0
Vascularization, Absent, Month 12 12
Vascularization, Mild, Month 12 1
Vascularization, Moderate, Month 12 0
Vascularization, Marked, Month 12 0
11.Secondary Outcome
Title Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Third Metacarpo-phalangeal Joint of Right Hand.
Hide Description The presence and severity of SH and JE of third MCP joint of right hand was determined by ultrasound examination. According to the method proposed by Naredo, SH and JE were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization of third MCP joint of right hand was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intraarticular surface).
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: participants
SH Absent, Baseline 26
SH Mild, Baseline 9
SH Moderate, Baseline 12
SH Marked, Baseline 6
SH Absent, Month 1 2
SH Mild, Month 1 1
SH Moderate, Month 1 2
SH Marked, Month 1 1
SH Absent, Month 2 4
SH Mild, Month 2 7
SH Moderate, Month 2 0
SH Marked, Month 2 0
SH Absent, Month 4 2
SH Mild, Month 4 4
SH Moderate, Month 4 2
SH Marked, Month 4 0
SH Absent, Month 6 6
SH Mild, Month 6 3
SH Moderate, Month 6 2
SH Marked, Month 6 0
SH Absent, Month 12 12
SH Mild, Month 12 1
SH Moderate, Month 12 0
SH Marked, Month 12 0
JE Absent, Baseline 26
JE Mild, Baseline 7
JE Moderate, Baseline 17
JE Marked, Baseline 4
JE Absent, Month 1 1
JE Mild, Month 1 1
JE Moderate, Month 1 3
JE Marked, Month 1 1
JE Absent, Month 2 6
JE Mild, Month 2 3
JE Moderate, Month 2 2
JE Marked, Month 2 0
JE Absent, Month 4 4
JE Mild, Month 4 6
JE Moderate, Month 4 0
JE Marked, Month 4 0
JE Absent, Month 6 8
JE Mild, Month 6 4
JE Moderate, Month 6 1
JE Marked, Month 6 0
JE Absent, Month 12 9
JE Mild, Month 12 4
JE Moderate, Month 12 0
JE Marked, Month 12 0
Vascularization, Absent, Baseline 27
Vascularization, Mild, Baseline 7
Vascularization, Moderate, Baseline 8
Vascularization, Marked, Baseline 10
Vascularization, Absent, Month 1 2
Vascularization, Mild, Month 1 1
Vascularization, Moderate, Month 1 2
Vascularization, Marked, Month 1 1
Vascularization, Absent, Month 2 4
Vascularization, Mild, Month 2 5
Vascularization, Moderate, Month 2 2
Vascularization, Marked, Month 2 0
Vascularization, Absent, Month 4 4
Vascularization, Mild, Month 4 5
Vascularization, Moderate, Month 4 0
Vascularization, Marked, Month 4 0
Vascularization, Absent, Month 6 8
Vascularization, Mild, Month 6 2
Vascularization, Moderate, Month 6 1
Vascularization, Marked, Month 6 0
Vascularization, Absent, Month 12 12
Vascularization, Mild, Month 12 1
Vascularization, Moderate, Month 12 0
Vascularization, Marked, Month 12 0
12.Secondary Outcome
Title Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Second Metacarpo-phalangeal Joint of Left Hand
Hide Description The presence and severity of SH and JE of second MCP joint of left hand was determined by ultrasound examination. According to the method proposed by Naredo, SH and JE were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization of second MCP joint of left hand was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intra-articular surface).
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents. Participants receiving treatment with TCZ with dose of 8 milligrams mg/kg body weight, intravenously once every 4 weeks for 12 months were observed. Dosage of TCZ was prescribed according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: participants
SH Absent, Baseline 24
SH Mild, Baseline 9
SH Moderate, Baseline 16
SH Marked, Baseline 3
SH Absent, Month 1 1
SH Mild, Month 1 1
SH Moderate, Month 1 3
SH Marked, Month 1 1
SH Absent, Month 2 2
SH Mild, Month 2 7
SH Moderate, Month 2 2
SH Marked, Month 2 0
SH Absent, Month 4 1
SH Mild, Month 4 5
SH Moderate, Month 4 3
SH Marked, Month 4 0
SH Absent, Month 6 6
SH Mild, Month 6 3
SH Moderate, Month 6 4
SH Marked, Month 6 0
SH Absent, Month 12 6
SH Mild, Month 12 5
SH Moderate, Month 12 2
SH Marked, Month 12 0
JE Absent, Baseline 22
JE Mild, Baseline 13
JE Moderate, Baseline 15
JE Marked, Baseline 3
JE Absent, Month 1 1
JE Mild, Month 1 1
JE Moderate, Month 1 3
JE Marked, Month 1 1
JE Absent, Month 2 5
JE Mild, Month 2 5
JE Moderate, Month 2 1
JE Marked, Month 2 0
JE Absent, Month 4 2
JE Mild, Month 4 6
JE Moderate, Month 4 1
JE Marked, Month 4 0
JE Absent, Month 6 8
JE Mild, Month 6 4
JE Moderate, Month 6 1
JE Marked, Month 6 0
JE Absent, Month 12 9
JE Mild, Month 12 4
JE Moderate, Month 12 0
JE Marked, Month 12 0
Vascularization, Absent, Baseline 26
Vascularization, Mild, Baseline 8
Vascularization, Moderate, Baseline 11
Vascularization, Marked, Baseline 8
Vascularization, Absent, Month 1 2
Vascularization, Mild, Month 1 1
Vascularization, Moderate, Month 1 2
Vascularization, Marked, Month 1 1
Vascularization, Absent, Month 2 5
Vascularization, Mild, Month 2 6
Vascularization, Moderate, Month 2 0
Vascularization, Marked, Month 2 0
Vascularization, Absent, Month 4 4
Vascularization, Mild, Month 4 3
Vascularization, Moderate, Month 4 2
Vascularization, Marked, Month 4 0
Vascularization, Absent, Month 6 7
Vascularization, Mild, Month 6 3
Vascularization, Moderate, Month 6 1
Vascularization, Marked, Month 6 0
Vascularization, Absent, Month 12 12
Vascularization, Mild, Month 12 1
Vascularization, Moderate, Month 12 0
Vascularization, Marked, Month 12 0
13.Secondary Outcome
Title Number of Participants With Presence and Severity of Synovial Hyperplasia, Joint Effusion and Vascularisation of Third Metacarpo-phalangeal Joint of Left Hand.
Hide Description The presence and severity of SH and JE of third MCP joint of left hand was determined by ultrasound examination. According to the method proposed by Naredo, SH and JE were evaluated based on scoring from 1 to 3 (1 = mild, 2 = moderate, 3 = marked). Vascularization of third MCP joint of left hand was evaluated with power doppler ultrasound and the score was assessed by a semi quantitative scale ranging from 0 to 3 (0 = normal; 1 = slight, evidence of a single flow signal; 2 = moderate, confluent vessels; 3 = marked, evidence of multiple flow signals in over half the intra-articular surface).
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 322
Measure Type: Number
Unit of Measure: participants
SH Absent, Baseline 25
SH Mild, Baseline 9
SH Moderate, Baseline 14
SH Marked, Baseline 5
SH Absent, Month 1 1
SH Mild, Month 1 1
SH Moderate, Month 1 3
SH Marked, Month 1 1
SH Absent, Month 2 2
SH Mild, Month 2 6
SH Moderate, Month 2 3
SH Marked, Month 2 0
SH Absent, Month 4 3
SH Mild, Month 4 4
SH Moderate, Month 4 3
SH Marked, Month 4 0
SH Absent, Month 6 5
SH Mild, Month 6 4
SH Moderate, Month 6 4
SH Marked, Month 6 0
SH Absent, Month 12 8
SH Mild, Month 12 4
SH Moderate, Month 12 1
SH Marked, Month 12 0
JE Absent, Baseline 25
JE Mild, Baseline 7
JE Moderate, Baseline 18
JE Marked, Baseline 3
JE, Absent, Month 1 1
JE Mild, Month 1 1
JE Moderate, Month 1 3
JE Marked, Month 1 1
JE Absent, Month 2 5
JE Mild, Month 2 5
JE Moderate, Month 2 1
JE Marked, Month 2 0
JE Absent, Month 4 4
JE Mild, Month 4 6
JE Moderate, Month 4 0
JE Marked, Month 4 0
JE Absent, Month 6 8
JE Mild, Month 6 4
JE Moderate, Month 6 0
JE Marked, Month 6 0
JE Absent, Month 12 11
JE Mild, Month 12 2
JE Moderate, Month 12 0
JE Marked, Month 12 0
Vascularization, Absent, Baseline 29
Vascularization, Mild, Baseline 8
Vascularization, Moderate, Baseline 9
Vascularization, Marked, Baseline 7
Vascularization, Absent, Month 1 2
Vascularization, Mild, Month 1 1
Vascularization, Moderate, Month 1 2
Vascularization, Marked, Month 1 1
Vascularization, Absent, Month 2 6
Vascularization, Mild, Month 2 5
Vascularization, Moderate, Month 2 0
Vascularization, Marked, Month 2 0
Vascularization, Absent, Month 4 4
Vascularization, Mild, Month 4 5
Vascularization, Moderate, Month 4 0
Vascularization, Marked, Month 4 0
Vascularization, Absent, Month 6 6
Vascularization, Mild, Month 6 3
Vascularization, Moderate, Month 6 2
Vascularization, Marked, Month 6 0
Vascularization, Absent, Month 12 12
Vascularization, Mild, Month 12 1
Vascularization, Moderate, Month 12 0
Vascularization, Marked, Month 12 0
14.Secondary Outcome
Title Mean Disease Activity Score Based on 28 Joint Count Score in the Participants With Inadequate Response to Disease Modifying Anti-Rheumatic Drugs and Anti-Tumor Necrosis Factors Agents
Hide Description The DAS28 index applies a mathematical formula based on the following parameters: 1. Tender joints count (28 joints), 2. Swollen joints count (28 joints) 3. ESR or CRP measurement, 4. Participant’s judgment on his own overall health status expressed by a VAS and calculates total score of 0 to approximately 10. The DAS28 scale ranges from 0 to 10, where scores below 2.6 indicate best disease control, scores above 5.1 indicate worse disease control. The response to therapy is defined according to the disease activity detected, compared to the previous clinical evaluation. The mean DAS28 scores were evaluated after the first infusion of TCZ in two different sub populations: participants with inadequate response (IR) to DMARD (DMARD-IR: group A) or to DMARD and anti-TNF drugs (DMARD + anti-TNF-IR: group B). Data allowing the evaluation of DAS28 was available for 81 participants in DMARD-IR group and 203 participants in DMARD + anti-TNF-IR group.
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. The "n" represents the number of participants analyzed at a specified time point.
Arm/Group Title DMARD-IR DMARD + Anti-TNF-IR
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 81 203
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; n = 81, 203 5.3  (1.1) 5.3  (1.3)
Month 1; n = 54, 150 3.6  (1.2) 3.7  (1.3)
Month 2; n = 62, 144 3.1  (1.3) 3.4  (1.3)
Month 4; n = 64, 127 3.0  (1.4) 3.1  (1.2)
Month 6; n = 65, 158 3.0  (1.2) 3.0  (1.2)
Month 12; n = 60, 125 2.7  (1.2) 2.6  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DMARD-IR, DMARD + Anti-TNF-IR
Comments At Baseline: mean difference of scores of DAS28 between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8080
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.3 to 0.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DMARD-IR, DMARD + Anti-TNF-IR
Comments At Month 1: mean difference of scores of DAS28 between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4884
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.5 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DMARD-IR, DMARD + Anti-TNF-IR
Comments At Month 2: mean difference of scores of DAS28 between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0947
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.7 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DMARD-IR, DMARD + Anti-TNF-IR
Comments At Month 4: mean difference of scores of DAS28 between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8181
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.4 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DMARD-IR, DMARD + Anti-TNF-IR
Comments At Month 6: mean difference of scores of DAS28 between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9721
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.4 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DMARD-IR, DMARD + Anti-TNF-IR
Comments At Month 12: mean difference of scores of DAS28 between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5832
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.5
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Mean Score of Fatigue Based on Visual Analogue Scale in the Participants With Inadequate Response to Disease Modifying Anti-Rheumatic Drugs and Anti-Tumor Necrosis Factors Agents
Hide Description VAS for fatigue is a 100 mm scale for participant’s assessment of their current level of fatigue: 0 mm corresponds to “no perception of fatigue”; 100 mm is the “maximum that may be perceived”. The mean VAS fatigue scores were evaluated after the first infusion of TCZ in two different sub populations, classified according to the previous pharmacological treatment: participants with inadequate response to DMARD (DMARD-IR: group A) or to DMARD and anti-TNF drugs (DMARD + anti-TNF-IR: group B). Data allowing the evaluation of fatigue (VAS) was available for 45 participants in DMARD-IR group and 113 participants in DMARD + anti-TNF-IR group.
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. The "n" represents the number of participants analyzed at a specified time point.
Arm/Group Title DMARD- IR DMARD + Anti-TNF- IR
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 45 113
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; n = 42, 113 62.3  (21.6) 58.7  (25.2)
Month 1; n = 34, 90 50.1  (24.2) 48.0  (25.4)
Month 2; n = 38, 88 50.6  (24.0) 44.1  (25.0)
Month 4; n = 45, 99 42.8  (22.9) 40.0  (24.8)
Month 6; n = 43, 111 48.4  (23.6) 34.7  (25.4)
Month 12; n = 45, 94 34.9  (19.9) 31.0  (24.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Baseline: mean difference of scores of fatigue between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4211
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.5
Confidence Interval (2-Sided) 95%
- 5.1 to 12.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 1: mean difference of scores of fatigue between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6749
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
- 7.9 to 12.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 2: mean difference of scores of fatigue between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1817
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.4
Confidence Interval (2-Sided) 95%
-3.0 to 15.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 4: mean difference of scores of fatigue between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5182
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
- 5.8 to 11.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 6: mean difference of scores of fatigue between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0025
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 13.7
Confidence Interval (2-Sided) 95%
4.9 to 22.6
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 12: mean difference of scores of fatigue between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3540
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
- 4.4 to 12.1
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Mean Score of Health Assessment Questionnaire in the Participants With Inadequate Response to Disease Modifying Anti-Rheumatic Drugs and Anti-Tumor Necrosis Factors Agents
Hide Description The HAQ is a participant-completed questionnaire specific for RA, recommended by the American college of Rheumatology for the evaluation of quality of life. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. There are 4 possible responses for each question: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do. To calculate HAQ, participant must have a component set score for at least 6 of 8 component set. The HAQ is the sum of the scores, divided by the number of component set that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). Data allowing the evaluation of HAQ was available for 73 participants in DMARD-IR group and 157 participants in DMARD + anti-TNF-IR group.
Time Frame Baseline, Month 1, Month 2, Month 4, Month 6, and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The total population included all participants who met all inclusion/exclusion criteria described in the study and received at least one dose of study medication. The “n” represents the number of participants analyzed at a specified time point.
Arm/Group Title DMARD- IR DMARD + Anti-TNF- IR
Hide Arm/Group Description:
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
Overall Number of Participants Analyzed 73 157
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline; n = 73, 157 1.5  (0.8) 1.5  (0.7)
Month 1; n = 52, 120 1.1  (0.7) 1.3  (0.7)
Month 2; n = 58, 123 1.2  (0.8) 1.2  (0.8)
Month 4; n = 62, 122 0.9  (0.8) 1.1  (0.7)
Month 6; n = 62, 126 1.0  (0.8) 1.0  (0.7)
Month 12; n = 54, 102 1.0  (0.8) 0.9  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Baseline: mean difference of scores of HAQ between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7343
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
- 0.2 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 1: mean difference of scores of HAQ between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1098
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value - 0.2
Confidence Interval (2-Sided) 95%
- 0.4 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 2: mean difference of scores of HAQ between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4932
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value - 0.1
Confidence Interval (2-Sided) 95%
- 0.3 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 4: mean difference of scores of HAQ between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2468
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
- 0.4 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 6: mean difference of scores of HAQ between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9639
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
- 0.2 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection DMARD- IR, DMARD + Anti-TNF- IR
Comments At Month 12: mean difference of scores of HAQ between the two groups was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6696
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
- 0.2 to 0.3
Estimation Comments [Not Specified]
Time Frame Up to 12 months
Adverse Event Reporting Description An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
 
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants with moderate to severe RA who had received TCZ treatment for 6 months prior to initiation of study and are inadequate responders to DMARDs and anti-TNFs agents were observed. Participants received treatment with TCZ with dose of 8 mg/kg body weight, intravenously once every 4 weeks for 12 months according to EU approved dosage, and SmPC.
All-Cause Mortality
Tocilizumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tocilizumab
Affected / at Risk (%)
Total   28/322 (8.70%) 
Blood and lymphatic system disorders   
Leucopenia  1  1/322 (0.31%) 
Hypocomplementaemia  1  1/322 (0.31%) 
Cardiac disorders   
Atrial fibrillation  1  1/322 (0.31%) 
Congenital, familial and genetic disorders   
Hydrocele  1  1/322 (0.31%) 
Endocrine disorders   
Goitre  1  1/322 (0.31%) 
Eye disorders   
Retinal detachment  1  1/322 (0.31%) 
Gastrointestinal disorders   
Abdominal pain  1  1/322 (0.31%) 
Rectal haemorrhage  1  1/322 (0.31%) 
Intestinal perforation  1  2/322 (0.62%) 
Infections and infestations   
Renal abscess  1  1/322 (0.31%) 
Bronchitis  1  1/322 (0.31%) 
Diarrhoea infectious  1  1/322 (0.31%) 
Pyelonephritis  1  1/322 (0.31%) 
Tuberculosis  1  1/322 (0.31%) 
Urosepsis  1  1/322 (0.31%) 
Injury, poisoning and procedural complications   
Wrist fracture  1  1/322 (0.31%) 
Upper limb fracture  1  1/322 (0.31%) 
Femur fracture  1  1/322 (0.31%) 
Spinal fracture  1  1/322 (0.31%) 
Investigations   
Fibrin D dimer increased  1  1/322 (0.31%) 
Red blood cell sedimentation rate increased  1  1/322 (0.31%) 
Musculoskeletal and connective tissue disorders   
Musculoskeletal chest pain  1  1/322 (0.31%) 
Intervertebral disc protrusion  1  1/322 (0.31%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Rectosigmoid cancer  1  1/322 (0.31%) 
Nervous system disorders   
Polyneuropathy  1  1/322 (0.31%) 
Psychiatric disorders   
Major depression  1  1/322 (0.31%) 
Renal and urinary disorders   
Renal failure acute  1  1/322 (0.31%) 
Reproductive system and breast disorders   
Gynaecomastia  1  1/322 (0.31%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/322 (0.31%) 
Laryngeal oedema  1  1/322 (0.31%) 
Interstitial lung disease  1  1/322 (0.31%) 
Chronic obstructive pulmonary disease  1  1/322 (0.31%) 
Pneumonia  1  2/322 (0.62%) 
Skin and subcutaneous tissue disorders   
Urticaria  1  1/322 (0.31%) 
Skin ulcer  1  1/322 (0.31%) 
Surgical and medical procedures   
Skin neoplasm excision  1  1/322 (0.31%) 
Vascular disorders   
Hypertensive crisis  1  1/322 (0.31%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tocilizumab
Affected / at Risk (%)
Total   99/322 (30.75%) 
Blood and lymphatic system disorders   
Leucopenia  1  20/322 (6.21%) 
Neutropenia  1  17/322 (5.28%) 
Infections and infestations   
Bronchitis  1  23/322 (7.14%) 
Influenza  1  16/322 (4.97%) 
Metabolism and nutrition disorders   
Hypercholesterolaemia  1  23/322 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
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: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 61 6878333
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01394276     History of Changes
Other Study ID Numbers: ML25728
First Submitted: July 13, 2011
First Posted: July 14, 2011
Results First Submitted: April 30, 2016
Results First Posted: June 7, 2016
Last Update Posted: June 7, 2016