Trial Outcomes & Findings for A Study to Evaluate Efficacy of Tocilizumab Administered as Monotherapy or in Combination With Methotrexate and/or Other Disease Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis (RA) Participants (NCT NCT01941940)

NCT ID: NCT01941940

Last Updated: 2017-07-11

Results Overview

The CDAI is a numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient's global assessment of disease activity (PtGDA) and physician global assessment of disease activity (PGDA) assessed on 0-10 centimeters (cm) visual analogue scale (VAS). Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score less than or equal to (\</=) 2.8 indicates disease remission, greater than (\>) 2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 227 participants
• Primary outcome timeframe: Baseline, Week 24
• Results posted on: 2017-07-11

Participant Flow

Out of a total of 288 participants screened, 60 participants were excluded due to screening failure and 1 participant did not receive study treatment based on investigator's decision. Thus, total 227 participants were included in the study.

Participant milestones

Measure	Tocilizumab Tocilizumab at a fixed dose of 162 milligrams (mg) was administered as subcutaneous (SC) injection alone or along with methotrexate and/or other non-biological Disease-Modifying Antirheumatic Drugs (DMARDs) irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Overall Study STARTED	227
Overall Study COMPLETED	194
Overall Study NOT COMPLETED	33

Reasons for withdrawal

Measure	Tocilizumab Tocilizumab at a fixed dose of 162 milligrams (mg) was administered as subcutaneous (SC) injection alone or along with methotrexate and/or other non-biological Disease-Modifying Antirheumatic Drugs (DMARDs) irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Overall Study Adverse Event	11
Overall Study Lost to Follow-up	2
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	15
Overall Study Death	1
Overall Study Other	1

Baseline Characteristics

A Study to Evaluate Efficacy of Tocilizumab Administered as Monotherapy or in Combination With Methotrexate and/or Other Disease Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis (RA) Participants

Baseline characteristics by cohort

Measure	Tocilizumab n=227 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Age, Continuous	54.7 years STANDARD_DEVIATION 12.12 • n=5 Participants
Sex: Female, Male Female	197 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

The CDAI is a numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient's global assessment of disease activity (PtGDA) and physician global assessment of disease activity (PGDA) assessed on 0-10 centimeters (cm) visual analogue scale (VAS). Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score less than or equal to (</=) 2.8 indicates disease remission, greater than (>) 2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

Outcome measures

Measure

Tocilizumab n=183 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

-21.6 units on a scale Standard Deviation 13.25

PRIMARY outcome

Timeframe: Baseline, Week 20

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

Outcome measures

Measure

Tocilizumab n=185 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Change From Baseline in CDAI at Week 20

-21.3 units on a scale Standard Deviation 12.87

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

Outcome measures

Measure

Tocilizumab n=191 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Change From Baseline in CDAI at Week 16

-20.2 units on a scale Standard Deviation 12.53

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

Outcome measures

Measure

Tocilizumab n=198 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Change From Baseline in CDAI at Week 12

-19.1 units on a scale Standard Deviation 12.46

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

Outcome measures

Measure

Tocilizumab n=203 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Change From Baseline in CDAI at Week 8

-17.7 units on a scale Standard Deviation 12.07

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

Outcome measures

Measure

Tocilizumab n=212 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Change From Baseline in CDAI at Week 4

-14.0 units on a scale Standard Deviation 11.57

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

Outcome measures

Measure

Tocilizumab n=218 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Change From Baseline in CDAI at Week 2

-9.1 units on a scale Standard Deviation 9.71

SECONDARY outcome

Timeframe: Baseline up to Week 52 (Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 38, and 52)

Population: FAS

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 during any two consecutive visits, not including the baseline visit indicates disease remission.

Outcome measures

Measure

Tocilizumab n=227 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Number of Participants Achieving Clinical Remission According to CDAI up to Week 52

10 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hour) and PtGDA assessed on 0-10 cm VAS. Higher scores indicate greater affectation due to disease activity. DAS28-ESR total score= 0-9.4. DAS28-ESR </=3.2 indicates low disease activity, DAS28-ESR >3.2 to 5.1 indicates moderate to high disease activity, and DAS28-ESR </=3.2 indicates remission.

Outcome measures

Measure	Tocilizumab n=216 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52 Baseline (n=216)	5.81 units on a scale Standard Deviation 1.080
Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52 Change at Week 2 (n=208)	-1.5 units on a scale Standard Deviation 1.04
Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52 Change at Week 24 (n=174)	-3.2 units on a scale Standard Deviation 1.47
Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52 Change at Week 52 (n=31)	-3.6 units on a scale Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

SDAI is a numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and C-reactive protein (CRP) in milligrams per deciliter (mg/dL). Higher scores indicate greater affectation due to disease activity. SDAI total score = 0-86. 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.

Outcome measures

Measure	Tocilizumab n=215 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52 Change at Week 52 (n=29)	-39.3 units on a scale Standard Deviation 26.82
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52 Baseline (n=215)	48.70 units on a scale Standard Deviation 45.790
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52 Change at Week 2 (n=203)	-26.5 units on a scale Standard Deviation 44.04
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52 Change at Week 24 (n=176)	-38.9 units on a scale Standard Deviation 48.75

SECONDARY outcome

Timeframe: Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The ACR 20, 50, and 70 responses: greater than or equal to (>/=) 20 percent (%), 50%, and 70% improvement in TJC and SJC (28 assessed joints), and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP or ESR at each visit.

Outcome measures

Measure	Tocilizumab n=222 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 2: ACR 20 (n=222)	18.5 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 2: ACR 50 (n=222)	6.3 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 2: ACR 70 (n=222)	11.7 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 24: ACR 20 (n=192)	8.3 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 24: ACR 50 (n=192)	4.7 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 24: ACR 70 (n=192)	65.6 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 52: ACR 20 (n=70)	0.0 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 52: ACR 50 (n=70)	0.0 percentage of participants
Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Week 52: ACR 70 (n=70)	40.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 </=3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to </=5.1 or change from baseline >0.6 to </=1.2 with DAS28 </=5.1; non-responders: change from baseline </=0.6 or change from baseline >0.6 and </=1.2 with DAS28 >5.1.

Outcome measures

Measure	Tocilizumab n=222 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 52: Moderate Response (n=70)	8.6 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 2: No Response (n=222)	32.4 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 2: Moderate Response (n=222)	50.5 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 2: Good Response (n=222)	17.1 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 24: No Response (n=192)	13.5 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 24: Moderate Response (n=192)	25.0 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 24: Good Response (n=192)	61.5 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 52: No Response (n=70)	55.7 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Week 52: Good Response (n=70)	35.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

TJC was defined as the total number of painful joints based on 68-joint assessment (TJC-68) and 28-joint assessment (TJC-28).

Outcome measures

Measure	Tocilizumab n=224 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-68, Baseline (n=223)	16.91 tender joints Standard Deviation 10.860
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-68, Change at Week 2 (n=218)	-5.4 tender joints Standard Deviation 8.38
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-68, Change at Week 24 (n=188)	-12.9 tender joints Standard Deviation 11.18
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-68, Change at Week 52 (n=69)	-16.5 tender joints Standard Deviation 10.35
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-28, Baseline (n=224)	11.32 tender joints Standard Deviation 6.241
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-28, Change at Week 2 (n=219)	-3.7 tender joints Standard Deviation 5.40
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-28, Change at Week 24 (n=189)	-8.6 tender joints Standard Deviation 6.62
Change From Baseline in Total TJC at Weeks 2, 24, and 52 TJC-28, Change at Week 52 (n=70)	-11.0 tender joints Standard Deviation 6.14

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

SJC was defined as the total number of swollen joints based on 66-joint assessment (SJC-66) and 28-joint assessment (SJC-28).

Outcome measures

Measure	Tocilizumab n=224 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-66, Baseline (n=223)	9.53 swollen joints Standard Deviation 6.713
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-66, Change at Week 2 (n=218)	-3.7 swollen joints Standard Deviation 4.94
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-66, Change at Week 24 (n=188)	-8.3 swollen joints Standard Deviation 6.73
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-66, Change at Week 52 (n=69)	-9.1 swollen joints Standard Deviation 6.66
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-28, Baseline (n=224)	7.90 swollen joints Standard Deviation 5.203
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-28, Change at Week 2 (n=219)	-2.9 swollen joints Standard Deviation 3.91
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-28, Change at Week 24 (n=189)	-6.7 swollen joints Standard Deviation 5.17
Change From Baseline in Total SJC at Weeks 2, 24, and 52 SJC-28, Change at Week 52 (n=70)	-7.6 swollen joints Standard Deviation 4.63

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. Higher scores indicate greater affectation due to disease activity. The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. Higher scores represent greater affectation due to disease activity. Correlation coefficient for relationship between DAS28-ESR and CDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.

Outcome measures

Measure	Tocilizumab n=213 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient Week 2 (n=213)	0.86514 correlation coefficient
Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient Week 24 (n=182)	0.86944 correlation coefficient
Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient Week 52 (n=32)	0.87301 correlation coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. Higher scores indicate greater affectation due to disease activity. SDAI is a numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. Higher scores indicate greater affectation due to disease activity. Correlation coefficient for relationship between DAS28-ESR and SDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.

Outcome measures

Measure	Tocilizumab n=213 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient Week 2 (n=213)	0.88118 correlation coefficient
Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient Week 24 (n=182)	0.87060 correlation coefficient
Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient Week 52 (n=31)	0.81995 correlation coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. Higher scores represent greater affectation due to disease activity. SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. Higher scores indicate greater affectation due to disease activity. Correlation coefficient for relationship between CDAI and SDAI at different time points is reported. Correlation coefficient value range= -1 to 1. Higher positive value indicates greater positive relationship and higher negative value indicates greater negative relationship.

Outcome measures

Measure	Tocilizumab n=213 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient Week 2 (n=213)	0.98602 correlation coefficient
Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient Week 24 (n=185)	0.97515 correlation coefficient
Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient Week 52 (n=31)	0.97389 correlation coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. The ACR 20, 50, and 70 responses: >/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between DAS28-ESR and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Outcome measures

Measure	Tocilizumab n=213 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: DAS28-ESR and ACR20 (n=213)	-1.02676 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: DAS28-ESR and ACR50 (n=213)	-1.31737 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: DAS28-ESR and ACR70 (n=213)	-1.50400 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: DAS28-ESR and ACR20 (n=182)	-1.71191 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: DAS28-ESR and ACR50 (n=182)	-1.54281 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: DAS28-ESR and ACR70 (n=182)	-1.43977 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: DAS28-ESR and ACR20 (n=32)	-2.05036 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: DAS28-ESR and ACR50 (n=32)	-2.05036 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: DAS28-ESR and ACR70 (n=32)	-2.05036 regression coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

DAS28-ESR is calculated from the TJC and SJC based on a 28-joint assessment, the ESR in mm/hour and PtGDA. DAS28-ESR total score= 0-9.4. EULAR response criteria (based on DAS28 score): Good responders (change from baseline >1.2 with DAS28 </=3.2); Moderate responders (change from baseline >1.2 with DAS28 >3.2 to </=5.1 or change from baseline >0.6 to </=1.2 with DAS28 </=5.1); Non-responders (change from baseline </=0.6 or change from baseline >0.6 and </=1.2 with DAS28 >5.1). Regression coefficient for relationship between DAS28-ESR and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Outcome measures

Measure	Tocilizumab n=213 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 2: DAS28-ESR and EULAR (n=213)	-1.62883 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 24: DAS28-ESR and EULAR (n=182)	-1.36226 regression coefficient
Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 52: DAS28-ESR and EULAR (n=32)	-1.47781 regression coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. The ACR 20, 50, and 70 responses: >/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between CDAI and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Outcome measures

Measure	Tocilizumab n=220 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: CDAI and ACR20 (n=220)	-9.65473 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: CDAI and ACR50 (n=220)	-10.67389 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: CDAI and ACR70 (n=220)	-13.38810 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: CDAI and ACR20 (n=186)	-13.18433 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: CDAI and ACR50 (n=186)	-11.95933 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: CDAI and ACR70 (n=186)	-11.18299 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: CDAI and ACR20 (n=32)	-18.94643 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: CDAI and ACR50 (n=32)	-18.94643 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: CDAI and ACR70 (n=32)	-18.94643 regression coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. CDAI total score = 0-76. EULAR response criteria (based on DAS28 score): Good responders (change from baseline >1.2 with DAS28 </=3.2); Moderate responders (change from baseline >1.2 with DAS28 >3.2 to </=5.1 or change from baseline >0.6 to </=1.2 with DAS28 </=5.1); Non-responders (change from baseline </=0.6 or change from baseline >0.6 and </=1.2 with DAS28 >5.1). Regression coefficient for relationship between CDAI and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Outcome measures

Measure	Tocilizumab n=220 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 2: CDAI and EULAR (n=220)	-10.97686 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 24: CDAI and EULAR (n=186)	-7.03184 regression coefficient
Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 52: CDAI and EULAR (n=32)	-9.46563 regression coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. The ACR 20, 50, and 70 responses: >/=20%, 50%, and 70% improvement in TJC and SJC, and 20%, 50%, 70% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit. Regression coefficients for relationship between SDAI and ACR responses (ACR20, ACR50, and ACR70) at different time points are reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Outcome measures

Measure	Tocilizumab n=213 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: SDAI and ACR50 (n=31)	-22.83519 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: SDAI and ACR20 (n=213)	-9.44923 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: SDAI and ACR50 (n=213)	-10.74230 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 2: SDAI and ACR70 (n=213)	-13.31421 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: SDAI and ACR20 (n=185)	-14.19790 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: SDAI and ACR50 (n=185)	-12.65454 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 24: SDAI and ACR70 (n=185)	-11.78067 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: SDAI and ACR20 (n=31)	-22.83519 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient Week 52: SDAI and ACR70 (n=31)	-22.83519 regression coefficient

SECONDARY outcome

Timeframe: Weeks 2, 24, 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS and CRP in mg/dL. SDAI total score= 0-86. EULAR response criteria (based on DAS28 score): Good responders (change from baseline >1.2 with DAS28 </=3.2); Moderate responders (change from baseline >1.2 with DAS28 >3.2 to </=5.1 or change from baseline >0.6 to </=1.2 with DAS28 </=5.1); Non-responders (change from baseline </=0.6 or change from baseline >0.6 and </=1.2 with DAS28 >5.1). Regression coefficient for relationship between SDAI and EULAR Good response at different time points is reported. Regression coefficient value range= not defined (any negative or positive value is possible). Higher positive value indicates greater extent of positive relationship and higher negative value indicates greater extent of negative relationship.

Outcome measures

Measure	Tocilizumab n=213 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 2: SDAI and EULAR (n=213)	-11.73463 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 24: SDAI and EULAR (n=185)	-7.32435 regression coefficient
Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient Week 52: SDAI and EULAR (n=31)	-9.64146 regression coefficient

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants with DMARDs dose reductions and/or discontinuation.

Percentage of DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.

Outcome measures

Measure	Tocilizumab n=148 DMARDs Dose Red/Dis Events Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons Safety	27.7 percentage of events
Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons Discomfort	9.5 percentage of events
Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons Lack of Efficacy	29.7 percentage of events
Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons Other Than Above	31.1 percentage of events
Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons Unknown	2.0 percentage of events

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants with non-DMARDs dose reductions and/or discontinuation.

Percentage of Non-DMARDs dose reduction and/or discontinuation (Red/Dis) events is reported by different reasons.

Outcome measures

Measure	Tocilizumab n=547 Non-DMARDs Dose Red/Dis Events Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons Safety	9.5 percentage of events
Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons Discomfort	1.3 percentage of events
Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons Lack of Efficacy	8.8 percentage of events
Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons Other Than Above	73.7 percentage of events
Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons Unknown	6.8 percentage of events

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

Participants answered the following question: "Considering all the ways your arthritis affects you, how are you feeling today." Participants responded by using a 0 - 100 millimeter (mm) VAS, where 0 mm = very well and 100 mm = very poorly.

Outcome measures

Measure	Tocilizumab n=226 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52 Change at Week 2 (n=220)	-10.6 mm Standard Deviation 20.99
Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52 Baseline (n=226)	61.31 mm Standard Deviation 23.526
Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52 Change at Week 24 (n=186)	-28.4 mm Standard Deviation 27.40
Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52 Change at Week 52 (n=32)	-38.4 mm Standard Deviation 27.65

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The physician assessed participant's current disease activity on a 0-100 mm VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity.

Outcome measures

Measure	Tocilizumab n=226 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52 Baseline (n=226)	57.36 mm Standard Deviation 19.228
Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52 Change at Week 2 (n=220)	-15.3 mm Standard Deviation 17.49
Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52 Change at Week 24 (n=186)	-38.0 mm Standard Deviation 25.13
Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52 Change at Week 52 (n=32)	-43.9 mm Standard Deviation 17.13

SECONDARY outcome

Timeframe: Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

Participants assessed their pain using a 0-100 mm VAS. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain.

Outcome measures

Measure	Tocilizumab n=226 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Participant Pain VAS Score at Weeks 2, 24, and 52 Baseline (n=226)	58.21 mm Standard Deviation 23.622
Participant Pain VAS Score at Weeks 2, 24, and 52 Change at Week 2 (n=220)	-11.4 mm Standard Deviation 22.38
Participant Pain VAS Score at Weeks 2, 24, and 52 Change at Week 24 (n=186)	-26.5 mm Standard Deviation 27.31
Participant Pain VAS Score at Weeks 2, 24, and 52 Change at Week 52 (n=32)	-36.0 mm Standard Deviation 26.82

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Outcome measures

Measure	Tocilizumab n=223 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52 Baseline (n=223)	1.04 units on a scale Standard Deviation 0.687
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52 Change at Week 2 (n=215)	-0.2 units on a scale Standard Deviation 0.44
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52 Change at Week 24 (n=183)	-0.4 units on a scale Standard Deviation 0.63
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52 Change at Week 52 (n=31)	-0.5 units on a scale Standard Deviation 0.69

SECONDARY outcome

Timeframe: Weeks 24 and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

The SF-HLQ assessed productivity losses related to health problems in individuals with paid or unpaid work and consisted of three modules (absenteeism from paid work, production losses without absenteeism from paid work and hindrance in the performance of paid and unpaid work). Any missed working days or number of worked days with reduced efficiency during the last month were reported.

Outcome measures

Measure	Tocilizumab n=69 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52 Week 24 (n=69)	6.4 days Standard Deviation 45.09
Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52 Week 52 (n=7)	0.3 days Standard Deviation 0.76

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

FACIT total score is sum of Functional Assessment of Cancer Therapy-General (FACT-G) score and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; additional concerns) score. FACT-G is a core questionnaire that evaluates quality of life (QoL) in cancer population. FACT-G consists of 27 questions grouped in 4 domains of general health-related QoL: physical well-being, social/family well-being, emotional well-being, and functional well-being; each item ranges from 0 (not at all) to 4 (very much). FACT-G score ranges between 0-108. FACIT-F is a 13-item questionnaire that evaluates self-reported fatigue and its impact upon daily activities. Each item ranges from 0 (Not at all) to 4 (Very much). The sum of all responses result in the FACIT total score with a total possible range of 0 (better score) to 160 (worse score). Negative change from baseline represents a better QoL.

Outcome measures

Measure	Tocilizumab n=207 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52 Baseline (n=207)	72.41 units on a scale Standard Deviation 16.806
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52 Change at Week 2 (n=196)	-5.8 units on a scale Standard Deviation 14.10
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52 Change at Week 24 (n=165)	-11.1 units on a scale Standard Deviation 18.60
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52 Change at Week 52 (n=60)	-43.8 units on a scale Standard Deviation 34.87

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 52

Population: Per-protocol analysis set (PPAS) included all participants in FAS without any major protocol violation and who completed 24 weeks of treatment period. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome; 'n'=participants evaluable at specified time point.

PSQI is a questionnaire with 18 questions to assess sleep quality. The 18 questions are distributed to 7 elements (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction). A participant indicates how frequently each item was experienced on a scale from 0 to 3. The global score is the sum score of all 7 elements and ranges from 0-21 with higher values indicating worse sleep quality. A score of >/=5 indicates poor sleepers.

Outcome measures

Measure	Tocilizumab n=103 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52 Change at Week 24 (n=73)	-0.7 units on a scale Standard Deviation 2.39
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52 Change at Week 52 (n=16)	-0.9 units on a scale Standard Deviation 2.42
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52 Baseline (n=103)	11.00 units on a scale Standard Deviation 2.719

SECONDARY outcome

Timeframe: Weeks 24 and 52

Population: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'n' signifies the number of participants evaluable at specified time point.

Treatment Compliance was calculated as (total actual doses taken for the period) / (total planned or prescribed dose for the period) x 100.

Outcome measures

Measure	Tocilizumab n=222 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records Week 24 (n=221)	94.9 percentage of planned dose Standard Deviation 10.20
Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records Week 52 (n=222)	94.7 percentage of planned dose Standard Deviation 10.12

SECONDARY outcome

Timeframe: Baseline up to 95 weeks

Population: FAS

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are AEs occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state. Following AEs were considered as AEs of special interest: anaphylactic reaction, hypersensitivity, stress cardiomyopathy, Gilbert's syndrome, gastrointestinal perforation, injection site erythema, injection site hypersensitivity, injection site irritation, injection site pruritus, arthritis bacterial, cellulitis, klebsiella infection, oral candidiasis, pneumonia, skin infection, vulvovaginal candidiasis, alanine aminotransferase increased, hepatic enzyme increased, brain neoplasm malignant, and urticaria.

Outcome measures

Measure

Tocilizumab n=227 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) of Special Interest

7.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 38, 52, at 8 weeks after last dose (up to Week 60), at early withdrawal (up to Week 52), at Follow-up Visits 1 (Week 64), 2 (Week 76), and 3 (Week 88)

Population: FAS; Here, 'n' signifies the number of participants evaluable at specified time point.

Percentage of participants with positive results for ATA against tocilizumab at different time points is reported.

Outcome measures

Measure	Tocilizumab n=227 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Baseline (n=227)	2.6 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Week 12 (n=6)	100.0 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Week 24 (n=179)	1.7 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Week 38 (n=6)	33.3 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Week 52 (n=161)	1.2 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab 8 Weeks After Last Dose (up to Week 60) (n=41)	2.4 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Early Withdrawal (up to Week 52) (n=31)	6.5 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Follow-up Visit 1 (Week 64) (n=16)	100.0 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Follow-up Visit 2 (Week 76) (n=11)	100.0 percentage of participants
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab Follow-up Visit 3 (Week 88) (n=3)	100.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)

Population: FAS; Here 'n' signifies the number of participants evaluable at specified time point.

Outcome measures

Measure	Tocilizumab n=227 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Mean Tocilizumab Concentration Baseline (n=2)	35.6 micrograms per milliliter (mcg/mL) Standard Deviation 48.89
Mean Tocilizumab Concentration Week 12 (n=186)	46.4 micrograms per milliliter (mcg/mL) Standard Deviation 23.01
Mean Tocilizumab Concentration Week 24 (n=177)	52.6 micrograms per milliliter (mcg/mL) Standard Deviation 28.21
Mean Tocilizumab Concentration Week 38 (n=169)	55.2 micrograms per milliliter (mcg/mL) Standard Deviation 30.55
Mean Tocilizumab Concentration Week 52 (n=165)	54.0 micrograms per milliliter (mcg/mL) Standard Deviation 29.00
Mean Tocilizumab Concentration Early Withdrawal (up to Week 52) (n=19)	24.8 micrograms per milliliter (mcg/mL) Standard Deviation 22.90
Mean Tocilizumab Concentration Follow-up Visit 2 (Week 76) (n=17)	49.2 micrograms per milliliter (mcg/mL) Standard Deviation 34.05

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)

Population: FAS; Here 'n' signifies the number of participants evaluable at specified time point.

Outcome measures

Measure	Tocilizumab n=227 Participants Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration Baseline (n=213)	43.6 nanograms per milliliter (ng/mL) Standard Deviation 49.30
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration Week 12 (n=189)	543.9 nanograms per milliliter (ng/mL) Standard Deviation 144.34
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration Week 24 (n=181)	536.3 nanograms per milliliter (ng/mL) Standard Deviation 144.32
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration Week 38 (n=171)	557.8 nanograms per milliliter (ng/mL) Standard Deviation 144.23
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration Week 52 (n=168)	539.4 nanograms per milliliter (ng/mL) Standard Deviation 147.04
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration Early Withdrawal (up to Week 52) (n=32)	329.1 nanograms per milliliter (ng/mL) Standard Deviation 257.30
Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration Follow-up Visit 2 (Week 76) (n=18)	523.4 nanograms per milliliter (ng/mL) Standard Deviation 161.14

Adverse Events

Tocilizumab

Serious events: 17 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab n=227 participants at risk Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Cardiac disorders Stress cardiomyopathy	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Infections and infestations Pneumonia	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Infections and infestations Skin infection	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Injury, poisoning and procedural complications Humerus fracture	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Injury, poisoning and procedural complications Wrist fracture	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Investigations Carcinoembryonic antigen increased	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Investigations Hepatic enzyme increased	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Reproductive system and breast disorders Ovarian cyst	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Vascular disorders Aneurysm	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Gastrointestinal disorders Gastrointestinal perforation	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Immune system disorders Anaphylactic reaction	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Infections and infestations Cellulitis	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Infections and infestations Diverticulitis	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Infections and infestations Klebsiella infection	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Product Issues Device breakage	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Surgical and medical procedures Bladder neoplasm surgery	0.44% 1/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.

Other adverse events

Measure	Tocilizumab n=227 participants at risk Tocilizumab at a fixed dose of 162 mg was administered as SC injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants could continue the study treatment with SC tocilizumab until it became commercially available in Italy (maximum up to 638 days).
Infections and infestations Influenza	10.1% 23/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Investigations Transaminases increased	6.6% 15/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Respiratory, thoracic and mediastinal disorders Cough	7.0% 16/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Infections and infestations Bronchitis	6.6% 15/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.
Infections and infestations Urinary tract infection	5.3% 12/227 • Day 1 up to approximately 95 weeks FAS; TEAEs are adverse events occurring between the first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pre-treatment state.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER