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A Study of Subcutaneous RoActemra/Actemra (Tocilizumab) as Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Patients With Active Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT01995201
Recruitment Status : Completed
First Posted : November 26, 2013
Results First Posted : January 26, 2018
Last Update Posted : January 26, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: DMARD
Drug: methotrexate
Drug: tocilizumab [RoActemra/Actemra]
Enrollment 401
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Hide Arm/Group Description Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks. Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks. Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48. Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48. Participants who did not achieve sustained clinical remission at Week 20 and Week 24 but achieve low disease activity (DAS 28-ESR ≤ 3.2) at Week 24 continued with initial treatment of tocilizumab as a single fixed dose monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48. Patients who achieved moderate EULAR response at Week 24 continued in the study with initial treatment as per investigator's judgement. Non responders, safety population.
Period Title: From Baseline Until Week 24
Started 74 327 0 0 0 0 0
Completed 64 281 0 0 0 0 0
Not Completed 10 46 0 0 0 0 0
Reason Not Completed
Adverse Event             4             15             0             0             0             0             0
Anaphylaxis or hypersensitivity reaction             0             3             0             0             0             0             0
Death             0             1             0             0             0             0             0
Lack of Efficacy             2             5             0             0             0             0             0
Lost to Follow-up             2             3             0             0             0             0             0
Withdrawal by Subject             2             8             0             0             0             0             0
Physician Decision             0             2             0             0             0             0             0
Protocol Violation             0             9             0             0             0             0             0
Period Title: From Week 24 Until Week 48
Started 0 0 89 90 95 67 2
Completed 0 0 84 89 89 59 0
Not Completed 0 0 5 1 6 8 2
Reason Not Completed
Adverse Event             0             0             2             1             1             3             1
Death             0             0             0             0             0             2             0
Lack of Efficacy             0             0             1             0             0             2             1
Lost to Follow-up             0             0             0             0             1             1             0
Withdrawal by Subject             0             0             1             0             1             0             0
Physician Decision             0             0             0             0             1             0             0
Protocol Violation             0             0             1             0             2             0             0
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy Total
Hide Arm/Group Description Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks. Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 74 327 401
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 74 participants 327 participants 401 participants
53.5  (12.7) 53.6  (12.2) 53.6  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 74 participants 327 participants 401 participants
Female
62
  83.8%
264
  80.7%
326
  81.3%
Male
12
  16.2%
63
  19.3%
75
  18.7%
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24
Hide Description The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
Time Frame Week 20 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were conducted on the Full Analysis Set (FAS), i.e. all patients included in the study who received at least one dose of SC TCZ.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
48.4
(35.75 to 61.27)
52.9
(46.83 to 58.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 1: Tocilizumab Monotherapy, Phase 1: Combination Therapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5231
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR)
Hide Description The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
Time Frame From week 24 up to week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: mm/hr
Week 24 Number Analyzed 89 participants 90 participants
-4.07  (1.03) -4.01  (1.13)
Week 28 Number Analyzed 87 participants 88 participants
-3.94  (1.22) -3.78  (1.31)
Week 32 Number Analyzed 86 participants 90 participants
-3.97  (1.38) -3.77  (1.17)
Week 36 Number Analyzed 86 participants 88 participants
-3.82  (1.53) -3.90  (1.16)
Week 40 Number Analyzed 84 participants 88 participants
-3.95  (1.26) -3.84  (1.19)
Week 44 Number Analyzed 82 participants 88 participants
-4.05  (1.17) -3.76  (1.17)
Week 48 Number Analyzed 82 participants 88 participants
-4.14  (1.24) -3.68  (1.32)
3.Secondary Outcome
Title Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48
Hide Description The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score.
Time Frame From week 28 up to week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 89 participants 90 participants
88.5
(79.88 to 94.35)
84.1
(74.75 to 91.02)
Week 32 Number Analyzed 87 participants 90 participants
87.2
(78.27 to 93.44)
81.1
(71.49 to 88.59)
Week 36 Number Analyzed 86 participants 89 participants
80.2
(70.25 to 88.04)
86.4
(77.39 to 92.75)
Week 40 Number Analyzed 84 participants 88 participants
82.1
(72.26 to 89.65)
80.7
(70.88 to 88.32)
Week 44 Number Analyzed 82 participants 89 participants
89.0
(80.18 to 94.86)
78.4
(68.35 to 86.47)
Week 48 Number Analyzed 84 participants 89 participants
91.5
(83.20 to 96.50)
73.9
(63.41 to 82.66)
4.Secondary Outcome
Title Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48
Hide Description The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score.
Time Frame From week 28 up to week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 88 participants 90 participants
96.6
(90.25 to 99.28)
96.6
(90.36 to 99.29)
Week 32 Number Analyzed 87 participants 90 participants
96.5
(90.14 to 99.27)
95.6
(89.01 to 98.78)
Week 36 Number Analyzed 86 participants 89 participants
93.0
(85.43 to 97.40)
97.7
(92.03 to 99.72)
Week 40 Number Analyzed 84 participants 88 participants
98.8
(93.54 to 99.97)
98.9
(93.83 to 99.97)
Week 44 Number Analyzed 82 participants 89 participants
98.8
(93.39 to 99.97)
95.5
(88.77 to 98.75)
Week 48 Number Analyzed 84 participants 89 participants
100.0 [1] 
(NA to NA)
95.5
(88.77 to 98.75)
[1]
NA because the central value is 100%
5.Secondary Outcome
Title Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24
Hide Description The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate [ESR]).
Time Frame From week 2 until week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
ACR20 - Week 2 Number Analyzed 74 participants 319 participants
27.0
(17.35 to 38.61)
31.7
(26.59 to 37.08)
ACR20 - Week 4 Number Analyzed 73 participants 312 participants
50.7
(38.72 to 62.60)
49.7
(44.00 to 55.37)
ACR20 - Week 8 Number Analyzed 73 participants 300 participants
67.1
(55.13 to 77.67)
67.0
(61.36 to 72.30)
ACR20 - Week 12 Number Analyzed 70 participants 296 participants
80.0
(68.73 to 88.61)
74.7
(69.31 to 79.52)
ACR20 - Week 16 Number Analyzed 69 participants 292 participants
79.7
(68.31 to 88.44)
75.7
(70.35 to 80.49)
ACR20 - Week 20 Number Analyzed 65 participants 284 participants
73.8
(61.46 to 83.97)
81.0
(75.93 to 85.38)
ACR20 - Week 24 Number Analyzed 64 participants 281 participants
79.7
(67.77 to 88.72)
83.3
(78.39 to 87.44)
ACR20 - LOCF visit Number Analyzed 74 participants 319 participants
77.0
(67.77 to 88.72)
79.0
(78.39 to 87.44)
ACR50 - week 2 Number Analyzed 74 participants 319 participants
9.5
(3.89 to 18.52)
13.2
(9.66 to 17.38)
ACR50 - week 4 Number Analyzed 73 participants 312 participants
20.5
(11.98 to 31.62)
25.3
(20.59 to 30.53)
ACR50 - week 8 Number Analyzed 73 participants 300 participants
37.0
(25.97 to 49.09)
41.3
(35.70 to 47.14)
ACR50 - week 12 Number Analyzed 70 participants 296 participants
51.4
(39.17 to 63.56)
52.7
(46.84 to 58.51)
ACR50 - week 16 Number Analyzed 69 participants 292 participants
53.6
(41.20 to 65.72)
52.4
(46.50 to 58.25)
ACR50 - week 20 Number Analyzed 65 participants 284 participants
58.5
(45.56 to 70.56)
58.5
(52.48 to 64.24)
ACR50 - week 24 Number Analyzed 64 participants 281 participants
59.4
(46.37 to 71.49)
58.7
(52.72 to 64.53)
ACR50 - LOCF visit Number Analyzed 74 participants 319 participants
55.4
(46.37 to 71.49)
54.2
(52.72 to 64.53)
ACR70 - week 2 Number Analyzed 74 participants 319 participants
5.4
(1.49 to 13.27)
2.8
(1.30 to 5.29)
ACR70 - week 4 Number Analyzed 73 participants 312 participants
12.3
(5.80 to 22.12)
10.6
(7.39 to 14.53)
ACR70 - week 8 Number Analyzed 73 participants 300 participants
17.8
(9.84 to 28.53)
22.7
(18.05 to 27.83)
ACR70 - week 12 Number Analyzed 70 participants 296 participants
32.9
(22.09 to 45.12)
27.0
(22.05 to 32.47)
ACR70 - week 16 Number Analyzed 69 participants 292 participants
29.0
(18.69 to 41.16)
32.2
(26.87 to 37.88)
ACR70 - week 20 Number Analyzed 65 participants 284 participants
33.8
(22.57 to 46.65)
36.6
(31.01 to 42.52)
ACR70 - week 24 Number Analyzed 64 participants 281 participants
40.6
(28.51 to 53.63)
37.7
(32.03 to 43.67)
ACR70 - LOCF visit Number Analyzed 74 participants 319 participants
37.8
(28.51 to 53.63)
33.9
(32.03 to 43.67)
ACR90 - week 2 Number Analyzed 74 participants 319 participants
1.4
(0.03 to 7.30)
0.9
(0.19 to 2.72)
ACR90 - week 4 Number Analyzed 73 participants 312 participants
2.7
(0.33 to 9.55)
1.6
(0.52 to 3.70)
ACR90 - week 8 Number Analyzed 73 participants 300 participants
6.8
(2.26 to 15.26)
7.3
(4.65 to 10.89)
ACR90 - week 12 Number Analyzed 70 participants 296 participants
12.9
(6.05 to 23.01)
8.8
(5.82 to 12.61)
ACR90 - week 16 Number Analyzed 69 participants 292 participants
13.0
(6.14 to 23.32)
12.0
(8.49 to 16.27)
ACR90 - week 20 Number Analyzed 65 participants 284 participants
13.8
(6.53 to 24.66)
13.7
(9.95 to 18.29)
ACR90 - week 24 Number Analyzed 64 participants 281 participants
23.4
(13.75 to 35.69)
16.7
(12.56 to 21.61)
ACR90 - LOCF visit Number Analyzed 74 participants 319 participants
20.3
(13.75 to 35.69)
15.0
(12.56 to 21.61)
6.Secondary Outcome
Title Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48
Hide Description The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate [ESR]).
Time Frame From week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
ACR20 - Week 28 Number Analyzed 88 participants 90 participants
90.0
(82.7 to 95.99)
92.2
(84.63 to 96.82)
ACR20 - Week 32 Number Analyzed 87 participants 90 participants
93.1
(85.59 to 97.43)
94.4
(87.51 to 98.17)
ACR20 - Week 36 Number Analyzed 86 participants 89 participants
84.9
(75.54 to 91.70)
91.0
(83.05 to 96.04)
ACR20 - Week 40 Number Analyzed 84 participants 88 participants
88.1
(79.19 to 94.14)
93.2
(85.75 to 97.46)
ACR20 - Week 44 Number Analyzed 82 participants 89 participants
91.5
(83.20 to 96.50)
91.0
(83.05 to 96.04)
ACR20 - Week 48 Number Analyzed 84 participants 89 participants
96.4
(89.92 to 99.26)
88.8
(80.31 to 94.48)
ACR20 - LOCF visit Number Analyzed 89 participants 90 participants
95.5
(88.89 to 98.76)
87.8
(79.18 to 93.74)
ACR50 - Week 28 Number Analyzed 88 participants 90 participants
79.5
(69.61 to 87.40)
81.1
(71.49 to 88.59)
ACR50 - Week 32 Number Analyzed 87 participants 90 participants
85.1
(75.80 to 91.80)
83.3
(74.00 to 90.36)
ACR50 - Week 36 Number Analyzed 86 participants 89 participants
74.4
(63.87 to 83.22)
83.1
(73.73 to 90.25)
ACR50 - Week 40 Number Analyzed 84 participants 88 participants
79.8
(69.59 to 87.75)
81.8
(72.16 to 89.24)
ACR50 - Week 44 Number Analyzed 82 participants 89 participants
80.5
(70.26 to 88.42)
78.7
(68.69 to 86.63)
ACR50 - Week 48 Number Analyzed 84 participants 89 participants
88.1
(79.19 to 94.14)
79.8
(69.93 to 87.55)
ACR50 - LOCF visit Number Analyzed 89 participants 90 participants
84.3
(75.02 to 91.12)
78.9
(69.01 to 86.79)
ACR70 - Week 28 Number Analyzed 88 participants 90 participants
59.1
(48.09 to 69.46)
57.8
(46.91 to 68.12)
ACR70 - Week 32 Number Analyzed 87 participants 90 participants
65.5
(54.56 to 75.39)
54.4
(43.60 to 64.98)
ACR70 - Week 36 Number Analyzed 86 participants 89 participants
61.6
(50.51 to 71.92)
62.9
(52.03 to 72.93)
ACR70 - Week 40 Number Analyzed 84 participants 88 participants
65.5
(54.31 to 75.52)
59.1
(48.09 to 69.46)
ACR70 - Week 44 Number Analyzed 82 participants 89 participants
67.1
(55.81 to 77.06)
59.6
(48.62 to 69.83)
ACR70 - Week 48 Number Analyzed 84 participants 89 participants
71.4
(60.53 to 80.76)
65.2
(54.33 to 74.96)
ACR70 - LOCF visit Number Analyzed 89 participants 90 participants
68.5
(57.83 to 77.97)
64.4
(53.65 to 74.26)
ACR90 - Week 28 Number Analyzed 88 participants 90 participants
27.3
(18.32 to 37.81)
32.2
(22.75 to 42.90)
ACR90 - Week 32 Number Analyzed 87 participants 90 participants
35.6
(25.65 to 46.62)
31.1
(21.77 to 41.74)
ACR90 - Week 36 Number Analyzed 86 participants 89 participants
33.7
(23.88 to 44.72)
30.3
(21.03 to 40.99)
ACR90 - Week 40 Number Analyzed 84 participants 88 participants
41.7
(31.00 to 52.94)
29.5
(20.29 to 40.22)
ACR90 - Week 44 Number Analyzed 82 participants 89 participants
34.1
(24.03 to 45.45)
27.0
(18.10 to 37.42)
ACR90 - Week 48 Number Analyzed 84 participants 89 participants
45.2
(34.34 to 56.48)
32.6
(23.02 to 43.34)
ACR90 - LOCF visit Number Analyzed 89 participants 90 participants
42.7
(32.26 to 53.63)
32.2
(22.75 to 42.90)
7.Secondary Outcome
Title Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24
Hide Description DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to =<1.2 with DAS28 ≤5.1.
Time Frame From week 2 until week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Unit of Measure: Number of participants
Good response - week 2 Number Analyzed 74 participants 319 participants
14 61
Moderate response - week 2 Number Analyzed 74 participants 319 participants
36 196
Good response - week 4 Number Analyzed 73 participants 312 participants
18 109
Moderate response - week 4 Number Analyzed 73 participants 312 participants
49 175
Good response - week 8 Number Analyzed 73 participants 300 participants
37 162
Moderate response - week 8 Number Analyzed 73 participants 300 participants
32 121
Good response - week 12 Number Analyzed 70 participants 296 participants
41 194
Moderate response - week 12 Number Analyzed 70 participants 296 participants
27 95
Good response - week 16 Number Analyzed 69 participants 292 participants
45 209
Moderate response - week 16 Number Analyzed 69 participants 292 participants
22 76
Good response - week 20 Number Analyzed 65 participants 284 participants
45 221
Moderate response - week 20 Number Analyzed 65 participants 284 participants
18 56
Good response - week 24 Number Analyzed 64 participants 281 participants
48 225
Moderate response - week 24 Number Analyzed 64 participants 281 participants
16 53
Good response - LOCF visit Number Analyzed 74 participants 327 participants
54 247
Moderate response - LOCF visit Number Analyzed 74 participants 327 participants
19 73
8.Secondary Outcome
Title Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48
Hide Description DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to =<1.2 with DAS28 ≤5.1.
Time Frame From week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Unit of Measure: Number of participants
Good response - week 28 Number Analyzed 88 participants 90 participants
82 77
Moderate response - week 28 Number Analyzed 88 participants 90 participants
5 10
Good response - week 32 Number Analyzed 87 participants 90 participants
79 81
Moderate response - week 32 Number Analyzed 87 participants 90 participants
6 9
Good response - week 36 Number Analyzed 86 participants 89 participants
75 80
Moderate response - week 36 Number Analyzed 86 participants 89 participants
9 8
Good response - week 40 Number Analyzed 84 participants 88 participants
75 81
Moderate response - week 40 Number Analyzed 84 participants 88 participants
9 7
Good response - week 44 Number Analyzed 82 participants 89 participants
78 75
Moderate response - week 44 Number Analyzed 82 participants 89 participants
4 13
Good response - week 48 Number Analyzed 84 participants 89 participants
78 73
Moderate response - week 48 Number Analyzed 84 participants 89 participants
4 15
Good response - LOCF visit Number Analyzed 89 participants 90 participants
84 74
Moderate response - LOCF visit Number Analyzed 89 participants 90 participants
5 16
9.Secondary Outcome
Title Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24
Hide Description Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: CDAI score
Baseline values Number Analyzed 74 participants 327 participants
33.06  (12.45) 32.06  (12.28)
Week 2 Number Analyzed 74 participants 319 participants
-7.54  (9.57) -8.62  (9.22)
Week 4 Number Analyzed 73 participants 312 participants
-13.03  (10.91) -13.23  (10.65)
Week 8 Number Analyzed 73 participants 299 participants
-18.06  (11.05) -18.46  (11.61)
Week 12 Number Analyzed 70 participants 296 participants
-21.56  (11.77) -20.60  (11.42)
Week 16 Number Analyzed 69 participants 290 participants
-23.01  (12.33) -21.79  (11.57)
Week 20 Number Analyzed 65 participants 284 participants
-24.07  (11.97) -22.88  (12.10)
Week 24 Number Analyzed 64 participants 281 participants
-25.80  (13.31) -23.43  (11.62)
LOCF visit Number Analyzed 74 participants 327 participants
-24.42  (13.50) -21.58  (12.85)
10.Secondary Outcome
Title Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48
Hide Description Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame From week 24 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: CDAI score
Baseline values Number Analyzed 89 participants 90 participants
29.27  (10.90) 29.64  (12.13)
Week 24 Number Analyzed 89 participants 90 participants
-25.54  (10.60) -25.34  (12.10)
Week 28 Number Analyzed 88 participants 89 participants
-24.75  (10.64) -24.01  (12.30)
Week 32 Number Analyzed 87 participants 90 participants
-24.56  (12.93) -25.12  (11.64)
Week 36 Number Analyzed 86 participants 88 participants
-23.90  (11.56) -25.45  (11.42)
Week 40 Number Analyzed 84 participants 88 participants
-25.16  (10.43) -25.45  (11.75)
Week 44 Number Analyzed 82 participants 89 participants
-25.45  (10.11) -25.26  (11.75)
Week 48 Number Analyzed 83 participants 89 participants
-26.44  (11.13) -25.13  (12.51)
LOCF visit Number Analyzed 89 participants 90 participants
-25.74  (11.29) -24.87  (12.67)
11.Secondary Outcome
Title Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24
Hide Description Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: SDAI score
Baseline values Number Analyzed 74 participants 324 participants
48.66  (31.48) 44.40  (22.91)
Week 2 Number Analyzed 72 participants 309 participants
-20.45  (19.01) -19.50  (18.75)
Week 4 Number Analyzed 70 participants 308 participants
-27.86  (23.54) -24.34  (20.98)
Week 8 Number Analyzed 72 participants 292 participants
-32.61  (26.84) -29.34  (21.96)
Week 12 Number Analyzed 70 participants 291 participants
-36.23  (27.04) -30.95  (23.58)
Week 16 Number Analyzed 69 participants 286 participants
-37.82  (31.09) -32.66  (22.79)
Week 20 Number Analyzed 64 participants 277 participants
-36.79  (25.47) -33.95  (23.05)
Week 24 Number Analyzed 63 participants 277 participants
-41.38  (31.51) -34.80  (22.44)
LOCF visit Number Analyzed 74 participants 324 participants
-39.15  (30.45) -32.73  (22.84)
12.Secondary Outcome
Title Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48
Hide Description Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Time Frame From week 24 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: SDAI score
Baseline values Number Analyzed 89 participants 89 participants
41.45  (24.90) 40.92  (21.42)
Week 24 Number Analyzed 88 participants 90 participants
-37.02  (24.60) -35.88  (20.71)
Week 28 Number Analyzed 86 participants 87 participants
-35.15  (25.90) -34.50  (20.66)
Week 32 Number Analyzed 86 participants 90 participants
-35.60  (26.97) -34.88  (20.53)
Week 36 Number Analyzed 86 participants 88 participants
-35.29  (26.55) -35.35  (20.07)
Week 40 Number Analyzed 83 participants 88 participants
-37.26  (25.48) -35.70  (19.80)
Week 44 Number Analyzed 82 participants 89 participants
-37.09  (25.17) -35.06  (21.77)
Week 48 Number Analyzed 82 participants 88 participants
-37.93  (26.32) -35.02  (21.74)
LOCF visit Number Analyzed 89 participants 90 participants
-36.93  (25.75) -34.69  (21.75)
13.Secondary Outcome
Title Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24
Hide Description TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: TJC
Baseline visit Number Analyzed 74 participants 327 participants
18.05  (12.98) 19.12  (13.38)
Week 2 Number Analyzed 74 participants 319 participants
-4.31  (7.56) -5.00  (8.06)
Week 4 Number Analyzed 73 participants 312 participants
-7.04  (11.77) -7.96  (9.43)
Week 8 Number Analyzed 73 participants 300 participants
-9.81  (10.37) -10.90  (11.10)
Week 12 Number Analyzed 70 participants 296 participants
-12.27  (10.47) -12.01  (10.88)
Week 16 Number Analyzed 69 participants 291 participants
-13.43  (12.35) -13.09  (11.02)
Week 20 Number Analyzed 65 participants 284 participants
-13.65  (11.73) -13.70  (11.48)
Week 24 Number Analyzed 64 participants 281 participants
-15.47  (13.35) -14.20  (11.46)
LOCF visit Number Analyzed 74 participants 327 participants
-14.36  (12.87) -13.19  (11.75)
14.Secondary Outcome
Title Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48
Hide Description TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration.
Time Frame From week 24 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: TJC
Baseline values Number Analyzed 89 participants 90 participants
15.42  (9.05) 15.97  (12.77)
Week 28 Number Analyzed 88 participants 90 participants
-13.66  (8.44) -12.88  (11.52)
Week 32 Number Analyzed 87 participants 90 participants
-13.40  (8.99) -13.88  (11.43)
Week 36 Number Analyzed 86 participants 89 participants
-13.13  (8.82) -13.78  (11.70)
Week 40 Number Analyzed 84 participants 88 participants
-14.06  (8.58) -14.49  (12.07)
Week 44 Number Analyzed 82 participants 89 participants
-14.32  (8.25) -13.93  (11.62)
Week 48 Number Analyzed 84 participants 89 participants
-14.40  (8.61) -13.43  (12.17)
LOCF visit Number Analyzed 89 participants 90 participants
-13.96  (8.68) -13.27  (12.20)
15.Secondary Outcome
Title Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24
Hide Description SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.SJC
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: SJC
Baseline values Number Analyzed 74 participants 327 participants
10.05  (7.99) 9.76  (6.64)
Week 2 Number Analyzed 74 participants 319 participants
-3.22  (4.40) -3.42  (5.10)
Week 4 Number Analyzed 73 participants 312 participants
-5.07  (5.58) -5.46  (5.41)
Week 8 Number Analyzed 73 participants 300 participants
-7.38  (6.47) -6.81  (6.03)
Week 12 Number Analyzed 70 participants 296 participants
-7.93  (7.13) -7.60  (6.00)
Week 16 Number Analyzed 69 participants 290 participants
-8.35  (7.71) -8.01  (6.05)
Week 20 Number Analyzed 65 participants 284 participants
-8.72  (7.56) -8.37  (6.50)
Week 24 Number Analyzed 64 participants 281 participants
-9.13  (7.66) -8.38  (6.59)
LOCF visit Number Analyzed 74 participants 327 participants
-8.47  (7.48) -7.71  (6.67)
16.Secondary Outcome
Title Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48
Hide Description SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling.
Time Frame From week 24 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: SJC
Baseline values Number Analyzed 89 participants 90 participants
9.28  (6.52) 9.23  (7.55)
Week 28 Number Analyzed 88 participants 90 participants
-8.64  (6.19) -8.14  (6.81)
Week 32 Number Analyzed 87 participants 90 participants
-8.54  (7.02) -8.62  (7.13)
Week 36 Number Analyzed 86 participants 89 participants
-8.48  (6.50) -8.38  (6.76)
Week 40 Number Analyzed 84 participants 88 participants
-8.85  (6.40) -8.51  (6.59)
Week 44 Number Analyzed 82 participants 89 participants
-8.73  (6.62) -8.62  (6.97)
Week 48 Number Analyzed 84 participants 89 participants
-9.06  (6.58) -8.72  (7.34)
LOCF visit Number Analyzed 89 participants 90 participants
-8.82  (6.51) -8.64  (7.33)
17.Secondary Outcome
Title Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48
Hide Description The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1 - Monotherapy - qw Phase 2 Arm A1- Combination Therapy - qw Phase 2 Arm A2 - Monotherapy - q2w Phase 2 Arm A2 - Combination Therapy - q2w
Hide Arm/Group Description:
Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy from Week 24 to Week 48.
Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every 2 weeks monotherapy from Week 24 to Week 48.
Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every 2 weeks in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 23 66 23 67
Mean (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 23 participants 65 participants 23 participants 67 participants
82.6
(61.22 to 95.05)
90.6
(80.70 to 96.48)
87.0
(66.41 to 97.22)
83.1
(71.73 to 91.24)
Week 32 Number Analyzed 22 participants 65 participants 23 participants 67 participants
81.8
(59.72 to 94.81)
89.1
(78.75 to 95.49)
78.3
(56.30 to 92.54)
82.1
(70.80 to 90.39)
Week 36 Number Analyzed 21 participants 65 participants 23 participants 67 participants
90.5
(69.62 to 98.83)
76.9
(64.81 to 86.47)
86.4
(65.09 to 97.09)
86.4
(75.69 to 93.57)
Week 40 Number Analyzed 20 participants 64 participants 23 participants 67 participants
85.0
(62.11 to 96.79)
81.3
(69.54 to 89.92)
77.3
(54.63 to 92.18)
81.8
(70.39 to 90.24)
Week 44 Number Analyzed 19 participants 63 participants 23 participants 67 participants
94.7
(73.97 to 99.87)
87.3
(76.50 to 94.35)
77.3
(54.63 to 92.18)
78.8
(66.98 to 87.89)
Week 48 Number Analyzed 20 participants 64 participants 23 participants 67 participants
100 [1] 
(NA to NA)
89.1
(78.75 to 95.49)
77.3
(54.63 to 92.18)
72.7
(60.36 to 82.97)
LOCF Visit Number Analyzed 23 participants 66 participants 23 participants 67 participants
91.3
(71.96 to 98.93)
89.4
(79.36 to 95.63)
73.9
(51.59 to 89.77)
73.1
(60.90 to 83.24)
[1]
CI unavailable because the central value is 100%
18.Secondary Outcome
Title Percentages of Patients With Remission (CDAI<2.8) Until Week 24
Hide Description Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Baseline visit Number Analyzed 74 participants 327 participants
0
(0 to 0)
0
(0 to 0)
Week 2 Number Analyzed 74 participants 319 participants
2.7
(0.33 to 9.42)
1.6
(0.51 to 3.62)
Week 4 Number Analyzed 73 participants 312 participants
2.7
(0.33 to 9.55)
5.1
(2.96 to 8.19)
Week 8 Number Analyzed 73 participants 300 participants
11.0
(4.85 to 20.46)
14.4
(10.61 to 18.88)
Week 12 Number Analyzed 70 participants 296 participants
15.7
(8.11 to 26.38)
19.3
(14.92 to 24.22)
Week 16 Number Analyzed 69 participants 292 participants
18.8
(10.43 to 30.06)
22.8
(18.06 to 28.02)
Week 20 Number Analyzed 65 participants 284 participants
27.7
(17.31 to 40.19)
26.8
(21.70 to 32.31)
Week 24 Number Analyzed 64 participants 281 participants
29.7
(18.91 to 42.42)
30.2
(24.93 to 35.99)
LOCF visit Number Analyzed 74 participants 327 participants
29.7
(19.66 to 41.48)
29.4
(24.48 to 34.62)
19.Secondary Outcome
Title Percentages of Patients With Remission (CDAI<2.8) Until Week 48
Hide Description Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame From week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 88 participants 90 participants
46.6
(35.88 to 57.54)
48.3
(37.59 to 59.16)
Week 32 Number Analyzed 87 participants 90 participants
48.3
(37.42 to 59.25)
45.6
(35.02 to 56.40)
Week 36 Number Analyzed 86 participants 89 participants
52.3
(41.27 to 63.21)
46.6
(35.88 to 57.54)
Week 40 Number Analyzed 84 participants 88 participants
52.4
(41.19 to 63.40)
45.5
(34.80 to 56.42)
Week 44 Number Analyzed 82 participants 89 participants
50.0
(38.75 to 61.25)
50.6
(39.75 to 61.33)
Week 48 Number Analyzed 84 participants 89 participants
59.0
(47.69 to 69.72)
53.9
(43.04 to 64.56)
LOCF Visit Number Analyzed 89 participants 90 participants
57.8
(46.91 to 68.12)
60.3
(52.77 to 67.56)
20.Secondary Outcome
Title Percentages of Patients With Remission (SDAI<3.3) Until Week 24
Hide Description Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Baseline visit Number Analyzed 74 participants 327 participants
0
(0 to 0)
0
(0 to 0)
Week 2 Number Analyzed 74 participants 319 participants
1.4
(0.04 to 7.50)
1.9
(0.71 to 4.14)
Week 4 Number Analyzed 73 participants 312 participants
2.9
(0.35 to 9.94)
4.8
(2.72 to 7.83)
Week 8 Number Analyzed 73 participants 300 participants
11.1
(4.92 to 20.72)
14.6
(10.75 to 19.13)
Week 12 Number Analyzed 70 participants 296 participants
14.3
(7.07 to 24.71)
18.8
(14.47 to 23.72)
Week 16 Number Analyzed 69 participants 292 participants
17.4
(9.32 to 28.41)
22.2
(17.56 to 27.47)
Week 20 Number Analyzed 65 participants 284 participants
28.1
(17.60 to 40.76)
25.8
(20.77 to 31.36)
Week 24 Number Analyzed 64 participants 281 participants
31.7
(20.58 to 44.69)
28.8
(23.53 to 34.49)
LOCF visit Number Analyzed 74 participants 327 participants
28.4
(18.50 to 40.05)
25.4
(20.75 to 30.46)
21.Secondary Outcome
Title Percentages of Patients With Remission (SDAI<3.3) Until Week 48
Hide Description Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Time Frame From week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 88 participants 90 participants
50.0
(39.02 to 60.98)
46.0
(35.23 to 57.00)
Week 32 Number Analyzed 87 participants 90 participants
48.8
(37.90 to 59.86)
45.6
(35.02 to 56.40)
Week 36 Number Analyzed 86 participants 89 participants
53.5
(42.41 to 64.32)
47.7
(36.96 to 58.65)
Week 40 Number Analyzed 84 participants 88 participants
55.4
(44.10 to 66.34)
44.3
(33.73 to 55.30)
Week 44 Number Analyzed 82 participants 89 participants
50.0
(38.75 to 61.25)
47.2
(36.51 to 58.06)
Week 48 Number Analyzed 84 participants 89 participants
52.4
(41.11 to 63.59)
47.7
(36.96 to 58.65)
LOCF Visit Number Analyzed 89 participants 90 participants
51.7
(40.48 to 62.41)
47.8
(37.13 to 58.57)
22.Secondary Outcome
Title Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24
Hide Description The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR is used to calculate the DAS28 score.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 2 Number Analyzed 74 participants 319 participants
21.6
(12.89 to 32.72)
21.5
(17.12 to 26.47)
Week 4 Number Analyzed 73 participants 300 participants
26.0
(16.45 to 37.62)
36.8
(31.39 to 42.41)
Week 8 Number Analyzed 74 participants 327 participants
50.7
(38.72 to 62.60)
55.4
(49.54 to 61.16)
Week 12 Number Analyzed 70 participants 296 participants
58.6
(46.17 to 70.23)
67.7
(62.01 to 73.00)
Week 16 Number Analyzed 69 participants 292 participants
66.7
(54.29 to 77.56)
72.4
(66.89 to 77.48)
Week 20 Number Analyzed 65 participants 284 participants
67.7
(54.95 to 78.77)
78.2
(72.91 to 82.83)
Week 24 Number Analyzed 64 participants 281 participants
75.0
(62.60 to 84.98)
81.1
(75.98 to 85.49)
LOCF visit Number Analyzed 74 participants 327 participants
73.0
(61.39 to 82.65)
74.0
(68.90 to 78.68)
23.Secondary Outcome
Title Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48
Hide Description The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR was used to calculate the DAS28 score.
Time Frame From week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 88 participants 90 participants
95.4
(88.64 to 98.73)
88.6
(80.09 to 94.41)
Week 32 Number Analyzed 87 participants 90 participants
91.9
(83.95 to 96.66)
92.2
(84.63 to 96.82)
Week 36 Number Analyzed 86 participants 89 participants
87.2
(78.27 to 93.44)
92.0
(84.30 to 96.74)
Week 40 Number Analyzed 84 participants 88 participants
89.3
(80.63 to 94.98)
92.0
(84.30 to 96.74)
Week 44 Number Analyzed 82 participants 89 participants
96.3
(89.68 to 99.24)
87.5
(78.73 to 93.59)
Week 48 Number Analyzed 84 participants 89 participants
95.1
(87.98 to 98.66)
86.4
(77.39 to 92.75)
LOCF Visit Number Analyzed 89 participants 90 participants
94.4
(87.37 to 98.15)
85.6
(76.57 to 92.08)
24.Secondary Outcome
Title Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24
Hide Description Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 2 Number Analyzed 74 participants 319 participants
13.5
(6.68 to 23.45)
16.9
(12.98 to 21.50)
Week 4 Number Analyzed 73 participants 312 participants
24.7
(15.32 to 36.14)
26.9
(22.08 to 32.21)
Week 8 Number Analyzed 73 participants 300 participants
41.1
(29.71 to 53.23)
47.5
(41.71 to 53.32)
Week 12 Number Analyzed 70 participants 296 participants
57.1
(44.75 to 68.91)
52.4
(46.51 to 58.17)
Week 16 Number Analyzed 69 participants 292 participants
62.3
(49.83 to 73.71)
60.7
(54.81 to 66.35)
Week 20 Number Analyzed 65 participants 284 participants
66.2
(53.35 to 77.43)
65.1
(59.29 to 70.68)
Week 24 Number Analyzed 64 participants 281 participants
71.9
(59.24 to 82.40)
66.9
(61.07 to 72.38)
LOCF visit Number Analyzed 74 participants 327 participants
66.2
(54.28 to 76.81)
61.2
(55.64 to 66.48)
25.Secondary Outcome
Title Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48
Hide Description Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
Time Frame From week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 88 participants 90 participants
86.4
(77.39 to 92.75)
85.4
(76.32 to 91.99)
Week 32 Number Analyzed 87 participants 90 participants
89.7
(81.27 to 95.16)
86.7
(77.87 to 92.92)
Week 36 Number Analyzed 86 participants 89 participants
80.2
(70.25 to 88.04)
89.8
(81.47 to 95.22)
Week 40 Number Analyzed 84 participants 88 participants
86.9
(77.78 to 93.28)
88.6
(80.09 to 94.41)
Week 44 Number Analyzed 82 participants 89 participants
89.0
(80.18 to 94.86)
85.4
(76.32 to 91.99)
Week 48 Number Analyzed 84 participants 89 participants
92.8
(84.93 to 97.30)
87.6
(78.96 to 93.67)
LOCF Visit Number Analyzed 89 participants 90 participants
91.0
(83.05 to 96.04)
87.8
(79.18 to 93.74)
26.Secondary Outcome
Title Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24
Hide Description Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 2 Number Analyzed 74 participants 319 participants
16.7
(8.92 to 27.30)
17.6
(13.56 to 22.32)
Week 4 Number Analyzed 73 participants 312 participants
27.1
(17.20 to 39.10)
28.3
(23.36 to 33.65)
Week 8 Number Analyzed 73 participants 300 participants
41.7
(30.15 to 53.89)
48.1
(42.31 to 54.00)
Week 12 Number Analyzed 70 participants 296 participants
58.6
(46.17 to 70.23)
55.6
(49.74 to 61.41)
Week 16 Number Analyzed 69 participants 292 participants
63.8
(51.31 to 75.01)
62.5
(56.63 to 68.11)
Week 20 Number Analyzed 65 participants 284 participants
65.6
(52.70 to 77.05)
66.3
(60.43 to 71.83)
Week 24 Number Analyzed 64 participants 281 participants
74.6
(62.06 to 84.73)
67.3
(61.41 to 72.75)
LOCF visit Number Analyzed 74 participants 327 participants
63.5
(51.51 to 74.40)
56.9
(51.32 to 62.32)
27.Secondary Outcome
Title Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48
Hide Description Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
Time Frame From week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 28 Number Analyzed 88 participants 90 participants
84.9
(75.54 to 91.70)
83.89
(74.48 to 90.91)
Week 32 Number Analyzed 87 participants 90 participants
89.5
(81.06 to 95.10)
85.6
(76.57 to 92.08)
Week 36 Number Analyzed 86 participants 89 participants
79.1
(68.95 to 87.10)
87.5
(78.73 to 93.59)
Week 40 Number Analyzed 84 participants 88 participants
86.7
(77.52 to 93.19)
86.4
(77.39 to 92.75)
Week 44 Number Analyzed 82 participants 89 participants
91.5
(83.20 to 96.50)
82.0
(72.45 to 89.36)
Week 48 Number Analyzed 84 participants 89 participants
93.9
(86.34 to 97.99)
81.8
(72.16 to 89.24)
LOCF Visit Number Analyzed 89 participants 90 participants
91.0
(83.05 to 96.04)
81.1
(71.49 to 88.59)
28.Secondary Outcome
Title Safety: Number of Patients Reporting Adverse Events up to Week 24
Hide Description Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 24
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Unit of Measure: Number of participants
Any treatment emergent adverse event (TEAE) 52 254
At least one TEAE of special interest 2 13
At least one serious TEAE 3 10
At least one TEAE leading to dose modification 24 103
At least one TEAE leading to discontinuation 4 21
29.Secondary Outcome
Title Safety: Number of Patients Reporting Adverse Events up to Week 48
Hide Description Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 48
Time Frame From week 24 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who did not achieve sustained clinical remission at Week 20 and Week 24 but achieve low disease activity (DAS 28-ESR ≤ 3.2) at Week 24 continued with initial treatment of tocilizumab as a single fixed dose monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Patients who achieved moderate EULAR response at Week 24 continued in the study with initial treatment as per investigator's judgement.
Patients who didn't achieve any therapeutic response up to week 24 and were discontinued from the study.
Overall Number of Participants Analyzed 89 90 95 67 2
Measure Type: Number
Unit of Measure: Number of participants
Any TEAE 50 63 68 46 1
At least one TEAE of special interest 1 2 2 4 0
At least one serious TEAE 2 1 2 5 1
At least one TEAE leading to dose modification 15 23 23 21 1
At least one TEAE leading to discontinuation 0 0 0 2 0
30.Secondary Outcome
Title Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24
Hide Description Number of patients resulting positive to anti-tocilizumab antibodies test are reported.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Measure Type: Number
Unit of Measure: Number of participants
Screen - Baseline 6 13
Screen - Week 12 1 2
Screen - Week 24 3 9
Confirmatory - Baseline 4 5
Confirmatory - Week 12 1 0
Confirmatory - Week 24 1 3
31.Secondary Outcome
Title Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48
Hide Description Number of patients resulting positive to anti-tocilizumab antibodies test are reported.
Time Frame From week 24 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who did not achieve sustained clinical remission at Week 20 and Week 24 but achieve low disease activity (DAS 28-ESR ≤ 3.2) at Week 24 continued with initial treatment of tocilizumab as a single fixed dose monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Patients who achieved moderate EULAR response at Week 24 continued in the study with initial treatment as per investigator's judgement.
Patients who didn't achieve any therapeutic response up to week 24 and were discontinued from the study.
Overall Number of Participants Analyzed 89 90 95 67 2
Measure Type: Number
Unit of Measure: Number of participants
Screen - Week 36 Number Analyzed 86 participants 89 participants 91 participants 59 participants 0 participants
0 0 0 2
Screen - Week 48 Number Analyzed 84 participants 89 participants 89 participants 59 participants 0 participants
1 3 2 3
Confirmatory - Week 36 Number Analyzed 86 participants 89 participants 88 participants 59 participants 0 participants
0 0 0 1
Confirmatory - Week 48 Number Analyzed 84 participants 89 participants 88 participants 59 participants 0 participants
0 0 0 1
32.Secondary Outcome
Title Immunogenicity: TCZ Levels up to Week 24
Hide Description Mean concentrations of TCZ in patients' blood are reported.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: mcg/ml
Baseline Number Analyzed 1 participants 4 participants
0.49 [1]   (NA) 0.67  (0.34)
Week 12 Number Analyzed 67 participants 285 participants
37.97  (20.11) 41.23  (20.89)
Week 24 Number Analyzed 62 participants 273 participants
46.42  (28.35) 46.87  (27.65)
[1]
Analysis was done for one participant only.
33.Secondary Outcome
Title Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit
Hide Description Mean concentrations of TCZ in patients' blood are reported.
Time Frame week 36 and early withdrawal visit
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who did not achieve sustained clinical remission at Week 20 and Week 24 but achieve low disease activity (DAS 28-ESR ≤ 3.2) at Week 24 continued with initial treatment of tocilizumab as a single fixed dose monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48. Participants who achieved moderate EULAR response at Week 24 continued in the study with initial treatment as per investigator's judgement.
Patients who achieved moderate EULAR response at Week 24 continued in the study with initial treatment as per investigator's judgement.
Patients who didn't achieve any therapeutic response up to week 24 and were discontinued from the study.
Overall Number of Participants Analyzed 89 90 95 67 2
Mean (Standard Deviation)
Unit of Measure: mcg/ml
Week 36 Number Analyzed 84 participants 86 participants 86 participants 55 participants 0 participants
48.47  (30.17) 16.77  (16.10) 41.89  (28.82) 48.33  (25.79)
Early withdrawal visit Number Analyzed 2 participants 1 participants 4 participants 2 participants 1 participants
36.45  (18.03) 19.20 [1]   (NA) 24.43  (20.83) 13.75  (4.60) 1.78 [1]   (NA)
[1]
Analysis was conducted for one participant only
34.Secondary Outcome
Title Immunogenicity: SIL-6R Levels up to Week 24
Hide Description Mean concentration of SIL-6R in patients' blood are reported.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: mcg/ml
Baseline Number Analyzed 74 participants 321 participants
42.85  (16.26) 39.29  (11.10)
Week 12 Number Analyzed 69 participants 290 participants
566.47  (210.49) 570.34  (228.54)
Week 24 Number Analyzed 63 participants 279 participants
570.49  (198.26) 565.34  (198.32)
35.Secondary Outcome
Title Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit
Hide Description Mean concentration of SIL-6R in patients' blood are reported.
Time Frame Baseline, Week 36 and Early Withdrawal Visit
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who did not achieve sustained clinical remission at Week 20 and Week 24 but achieve low disease activity (DAS 28-ESR ≤ 3.2) at Week 24 continued with initial treatment of tocilizumab as a single fixed dose monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Patients who achieved moderate EULAR response at Week 24 continued in the study with initial treatment as per investigator's judgement.
Patients who didn't achieve any therapeutic response up to week 24 and were discontinued from the study.
Overall Number of Participants Analyzed 89 90 95 67 2
Mean (Standard Deviation)
Unit of Measure: mcg/ml
Baseline Number Analyzed 88 participants 88 participants 94 participants 67 participants 2 participants
39.87  (10.46) 39.70  (16.46) 39.39  (11.24) 43.11  (11.85) 37.30  (11.46)
Week 36 Number Analyzed 86 participants 89 participants 88 participants 59 participants 0 participants
539.89  (152.71) 476.28  (156.50) 542.99  (168.30) 552.65  (184.21)
Early withdrawal visit Number Analyzed 3 participants 1 participants 6 participants 5 participants 1 participants
412.53  (323.49) 643.00 [1]   (NA) 338.38  (230.82) 217.74  (236.21) 513.00 [1]   (NA)
[1]
Analysis was conducted on one participant only.
36.Secondary Outcome
Title Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24
Hide Description This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end as "maximum disease activity" (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: Millimeters
Baseline Number Analyzed 74 participants 319 participants
65.26  (19.77) 59.40  (17.61)
Week 2 Number Analyzed 74 participants 319 participants
49.53  (22.78) 44.16  (21.97)
Week 4 Number Analyzed 73 participants 312 participants
38.21  (22.92) 35.19  (20.83)
Week 8 Number Analyzed 73 participants 300 participants
30.03  (21.65) 26.04  (20.59)
Week 12 Number Analyzed 70 participants 296 participants
22.71  (18.56) 22.24  (17.97)
Week 16 Number Analyzed 69 participants 291 participants
19.28  (18.22) 20.71  (18.65)
Week 20 Number Analyzed 65 participants 284 participants
16.80  (16.68) 18.79  (17.79)
Week 24 Number Analyzed 64 participants 281 participants
16.63  (15.19) 19.00  (18.36)
LOCF visit Number Analyzed 74 participants 327 participants
20.36  (19.25) 22.23  (20.86)
37.Secondary Outcome
Title Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48
Hide Description This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end as "maximum disease activity" (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported.
Time Frame Baseline, from week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: Millimeters
Baseline Number Analyzed 89 participants 90 participants
58.97  (17.40) 60.96  (20.13)
Week 28 Number Analyzed 88 participants 90 participants
11.97  (14.10) 12.74  (15.07)
Week 32 Number Analyzed 87 participants 90 participants
10.78  (15.33) 10.80  (11.36)
Week 36 Number Analyzed 86 participants 89 participants
11.99  (16.23) 10.30  (13.20)
Week 40 Number Analyzed 84 participants 88 participants
10.62  (13.49) 10.94  (14.12)
Week 44 Number Analyzed 82 participants 89 participants
9.50  (11.30) 10.06  (12.14)
Week 48 Number Analyzed 84 participants 89 participants
8.13  (10.52) 9.99  (13.88)
LOCF visit Number Analyzed 89 participants 90 participants
8.97  (11.63) 10.21  (13.96)
38.Secondary Outcome
Title Assessment of Pain Reported by the Patient (VAS) Until Week 24
Hide Description This patient reported outcome assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no pain" and the extreme right end as "unbearable pain".
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: Millimeters
Baseline Number Analyzed 74 participants 327 participants
66.38  (20.70) 58.59  (23.70)
Week 2 Number Analyzed 74 participants 319 participants
53.20  (24.43) 47.46  (25.14)
Week 4 Number Analyzed 73 participants 312 participants
43.11  (24.69) 42.88  (24.57)
Week 8 Number Analyzed 73 participants 300 participants
35.95  (24.62) 34.28  (25.94)
Week 12 Number Analyzed 70 participants 296 participants
29.44  (22.37) 31.07  (24.97)
Week 16 Number Analyzed 69 participants 292 participants
32.17  (22.01) 30.18  (24.00)
Week 20 Number Analyzed 65 participants 284 participants
26.58  (22.13) 28.26  (24.16)
Week 24 Number Analyzed 64 participants 281 participants
23.56  (21.17) 26.43  (23.30)
LOCF visit Number Analyzed 74 participants 327 participants
27.34  (24.41) 29.78  (25.18)
39.Secondary Outcome
Title Assessment of Pain Reported by the Patient (VAS) Until Week 48
Hide Description This patient reported outcome assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no pain" and the extreme right end as "unbearable pain".
Time Frame Baseline, from week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: Millimeters
Baseline Number Analyzed 89 participants 90 participants
55.73  (21.68) 56.00  (23.56)
Week 28 Number Analyzed 88 participants 90 participants
17.33  (20.14) 15.67  (17.65)
Week 32 Number Analyzed 87 participants 90 participants
17.08  (20.47) 17.27  (17.69)
Week 36 Number Analyzed 86 participants 88 participants
18.81  (23.88) 14.36  (15.65)
Week 40 Number Analyzed 84 participants 88 participants
16.96  (20.89) 17.07  (17.86)
Week 44 Number Analyzed 82 participants 89 participants
15.05  (18.02) 16.27  (17.70)
Week 48 Number Analyzed 84 participants 89 participants
11.90  (15.56) 16.31  (19.85)
LOCF visit Number Analyzed 89 participants 90 participants
12.74  (15.99) 16.41  (19.76)
40.Secondary Outcome
Title Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24
Hide Description

The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.

Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: HAQ-DI score
Baseline Number Analyzed 74 participants 324 participants
1.49  (0.76) 1.36  (0.70)
Week 2 Number Analyzed 73 participants 317 participants
1.39  (0.74) 1.18  (0.69)
Week 4 Number Analyzed 72 participants 309 participants
1.20  (0.74) 1.05  (0.69)
Week 8 Number Analyzed 73 participants 300 participants
1.10  (0.75) 0.95  (0.71)
Week 12 Number Analyzed 69 participants 295 participants
0.99  (0.74) 0.91  (0.71)
Week 16 Number Analyzed 69 participants 292 participants
0.99  (0.72) 0.87  (0.70)
Week 20 Number Analyzed 65 participants 283 participants
0.88  (0.70) 0.83  (0.71)
Week 24 Number Analyzed 63 participants 281 participants
0.85  (0.71) 0.82  (0.70)
LOCF visit Number Analyzed 74 participants 327 participants
0.97  (0.76) 0.88  (0.73)
41.Secondary Outcome
Title Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48
Hide Description

The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.

Time Frame Baseline, from week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: HAQ-DI score
Baseline Number Analyzed 88 participants 89 participants
1.21  (0.68) 1.20  (0.70)
Week 28 Number Analyzed 88 participants 90 participants
0.58  (0.56) 0.57  (0.64)
Week 32 Number Analyzed 87 participants 90 participants
0.55  (0.58) 0.57  (0.63)
Week 36 Number Analyzed 86 participants 88 participants
0.60  (0.60) 0.56  (0.64)
Week 40 Number Analyzed 84 participants 88 participants
0.55  (0.56) 0.61  (0.67)
Week 44 Number Analyzed 82 participants 89 participants
0.53  (0.57) 0.58  (0.66)
Week 48 Number Analyzed 84 participants 89 participants
0.53  (0.61) 0.57  (0.66)
LOCF visit Number Analyzed 89 participants 90 participants
0.55  (0.61) 0.56  (0.66)
42.Secondary Outcome
Title Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24
Hide Description The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy
Hide Arm/Group Description:
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks.
Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks.
Overall Number of Participants Analyzed 74 327
Mean (Standard Deviation)
Unit of Measure: FACIT-F score
Baseline Number Analyzed 74 participants 327 participants
81.72  (24.75) 89.16  (24.49)
Week 2 Number Analyzed 74 participants 319 participants
86.64  (25.00) 95.82  (25.42)
Week 4 Number Analyzed 73 participants 312 participants
92.26  (25.30) 99.54  (27.15)
Week 8 Number Analyzed 73 participants 300 participants
96.45  (25.88) 103.46  (27.25)
Week 12 Number Analyzed 70 participants 296 participants
98.29  (25.47) 104.08  (26.79)
Week 16 Number Analyzed 69 participants 292 participants
98.41  (27.08) 105.51  (26.94)
Week 20 Number Analyzed 65 participants 284 participants
102.46  (27.24) 104.91  (27.47)
Week 24 Number Analyzed 64 participants 281 participants
104.36  (27.16) 107.01  (27.60)
LOCF visit Number Analyzed 74 participants 327 participants
101.38  (28.24) 104.65  (28.07)
43.Secondary Outcome
Title Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48
Hide Description The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions.
Time Frame Baseline, from week 28 until week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted on the FAS.
Arm/Group Title Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w)
Hide Arm/Group Description:
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Participants who achieve sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 will be randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48.
Overall Number of Participants Analyzed 89 90
Mean (Standard Deviation)
Unit of Measure: FACIT-F score
Baseline Number Analyzed 89 participants 90 participants
17.36  (5.16) 17.13  (5.67)
Week 28 Number Analyzed 88 participants 90 participants
23.50  (3.82) 23.12  (4.47)
Week 32 Number Analyzed 87 participants 90 participants
23.62  (4.16) 22.98  (4.86)
Week 36 Number Analyzed 86 participants 88 participants
23.23  (4.21) 22.90  (4.64)
Week 40 Number Analyzed 84 participants 88 participants
23.39  (4.40) 23.02  (4.38)
Week 44 Number Analyzed 82 participants 89 participants
23.48  (4.21) 23.13  (4.45)
Week 48 Number Analyzed 84 participants 89 participants
23.95  (3.79) 22.87  (4.87)
LOCF visit Number Analyzed 89 participants 90 participants
23.69  (4.07) 22.88  (4.85)
Time Frame After initiation of study drug, all AEs, regardless of relationship to study drug, are reported until study closure.
Adverse Event Reporting Description

In this section the arms are not mutually exclusive because they report AE data across two different phases of the study. The patients in phase 2 groups B,C and D were considered in this study for safety reporting purposes only.

In Non Serious Adverse events section data was calculated separately according to the two different phases of the study, i.e. Phase 1 mono-therapy and Phase 1 combination therapy groups, and the Phase 2 groups.

 
Arm/Group Title Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Hide Arm/Group Description Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection as a single fixed dose monotherapy once a week for 24 weeks. Participants received Tocilizumab (TCZ), 162mg, by sub-cutaneous injection in combination with oral or sub-cutaneous methotrexate (MTX) or other non-biologic Disease Modifying Anti Rheumatic Drugs (nbDMARDs) once a week for 24 weeks. Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every week monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48. Participants who achieved sustained clinical remission (DAS28-ESR <2.6) at Week 20 and Week 24 in Part 1 were randomized to tocilizumab given every 2 weeks monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48. Participants who did not achieve sustained clinical remission at Week 20 and Week 24 but achieve low disease activity (DAS 28-ESR ≤ 3.2) at Week 24 continued with initial treatment of tocilizumab as a single fixed dose monotherapy or in combination with methotrexate or other non-biologics DMARDs from Week 24 to Week 48. Patients who achieved moderate EULAR response at Week 24 continued in the study with initial treatment as per investigator's judgement. Patients who didn't achieve any therapeutic response up to week 24 and were discontinued from the study.
All-Cause Mortality
Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/74 (0.00%)   1/327 (0.31%)   0/89 (0.00%)   0/90 (0.00%)   0/95 (0.00%)   2/67 (2.99%)   0/2 (0.00%) 
Hide Serious Adverse Events
Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/74 (4.05%)   10/327 (3.06%)   2/89 (2.25%)   1/90 (1.11%)   2/95 (2.11%)   5/67 (7.46%)   1/2 (50.00%) 
Blood and lymphatic system disorders               
Neutropenia * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Cardiac disorders               
Pericarditis * 1  1/74 (1.35%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Acute coronary syndrome * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  1/95 (1.05%)  0/67 (0.00%)  0/2 (0.00%) 
Coronary artery disease * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  1/67 (1.49%)  0/2 (0.00%) 
Myocardial infarction * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  1/67 (1.49%)  0/2 (0.00%) 
Gastrointestinal disorders               
Duodenal perforation * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Intestinal obstruction * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Ascites * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  1/2 (50.00%) 
Diverticular perforation * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  1/90 (1.11%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Ileus * 1  0/74 (0.00%)  0/327 (0.00%)  1/89 (1.12%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Hepatobiliary disorders               
Biliary fistula * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Infections and infestations               
Breast abscess * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  1/95 (1.05%)  0/67 (0.00%)  0/2 (0.00%) 
Abscess limb * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Pneumonia * 1  0/74 (0.00%)  2/327 (0.61%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Pyelonephritis acute * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Injury, poisoning and procedural complications               
Spinal fracture * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  1/67 (1.49%)  0/2 (0.00%) 
Musculoskeletal and connective tissue disorders               
Rheumatoid arthritis * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  1/67 (1.49%)  0/2 (0.00%) 
Back pain * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Metastatic malignant melanoma * 1  0/74 (0.00%)  0/327 (0.00%)  1/89 (1.12%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Invasive ductal breast carcinoma * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Urinary tract neoplasm * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Nervous system disorders               
Headache * 1  1/74 (1.35%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Interstitial lung disease * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Pulmonary embolism * 1  0/74 (0.00%)  2/327 (0.61%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Vascular disorders               
Deep vein thrombosis * 1  1/74 (1.35%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Thrombophlebitis * 1  0/74 (0.00%)  1/327 (0.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Hypertensive crisis * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  1/67 (1.49%)  0/2 (0.00%) 
1
Term from vocabulary, MedDRA version 18.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1: Tocilizumab Monotherapy Phase 1: Combination Therapy Phase 2 Arm A1: TCZ +/- nbDMARD Once Per Week (qw) Phase 2 Arm A2: TCZ +/- nbDMARD Every Two Weeks (q2w) Phase 2 Arm B: Participants With Low Disease Activity Phase 2 Arm C: Moderate EULAR Response at Week 24 Phase 2 Arm D: Non Responders
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/74 (32.43%)   119/327 (36.39%)   17/89 (19.10%)   25/90 (27.78%)   30/95 (31.58%)   23/67 (34.33%)   0/2 (0.00%) 
Blood and lymphatic system disorders               
Neutropenia * 1  4/74 (5.41%)  18/327 (5.50%)  1/89 (1.12%)  5/90 (5.56%)  3/95 (3.16%)  2/67 (2.99%)  0/2 (0.00%) 
Thrombocytopenia * 1  4/74 (5.41%)  9/327 (2.75%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Gastrointestinal disorders               
Nausea * 1  1/74 (1.35%)  18/327 (5.50%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
General disorders               
Injection site erythema * 1  6/74 (8.11%)  10/327 (3.06%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Oedema peripheral * 1  0/74 (0.00%)  0/327 (0.00%)  0/89 (0.00%)  1/90 (1.11%)  3/95 (3.16%)  4/67 (5.97%)  0/2 (0.00%) 
Infections and infestations               
Upper respiratory tract infection * 1  2/74 (2.70%)  23/327 (7.03%)  9/89 (10.11%)  7/90 (7.78%)  3/95 (3.16%)  4/67 (5.97%)  0/2 (0.00%) 
Urinary tract infection * 1  6/74 (8.11%)  23/327 (7.03%)  3/89 (3.37%)  2/90 (2.22%)  8/95 (8.42%)  3/67 (4.48%)  0/2 (0.00%) 
Nasopharyngitis * 1  0/74 (0.00%)  0/327 (0.00%)  2/89 (2.25%)  4/90 (4.44%)  5/95 (5.26%)  4/67 (5.97%)  0/2 (0.00%) 
Respiratory tract infection * 1  0/74 (0.00%)  0/327 (0.00%)  2/89 (2.25%)  3/90 (3.33%)  5/95 (5.26%)  3/67 (4.48%)  0/2 (0.00%) 
Investigations               
Transaminases increased * 1  1/74 (1.35%)  37/327 (11.31%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Musculoskeletal and connective tissue disorders               
Back pain * 1  4/74 (5.41%)  15/327 (4.59%)  0/89 (0.00%)  0/90 (0.00%)  0/95 (0.00%)  0/67 (0.00%)  0/2 (0.00%) 
Rheumatoid arthritis * 1  0/74 (0.00%)  0/327 (0.00%)  2/89 (2.25%)  3/90 (3.33%)  6/95 (6.32%)  3/67 (4.48%)  0/2 (0.00%) 
Nervous system disorders               
Headache * 1  0/74 (0.00%)  0/327 (0.00%)  2/89 (2.25%)  1/90 (1.11%)  0/95 (0.00%)  4/67 (5.97%)  0/2 (0.00%) 
Vascular disorders               
Hypertension * 1  0/74 (0.00%)  0/327 (0.00%)  2/89 (2.25%)  1/90 (1.11%)  5/95 (5.26%)  1/67 (1.49%)  0/2 (0.00%) 
1
Term from vocabulary, MedDRA version 18.1
*
Indicates events were collected by non-systematic assessment
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.
Results Point of Contact
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Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01995201    
Other Study ID Numbers: ML28709
2013-002429-52 ( EudraCT Number )
First Submitted: November 1, 2013
First Posted: November 26, 2013
Results First Submitted: March 8, 2017
Results First Posted: January 26, 2018
Last Update Posted: January 26, 2018