Trial Outcomes & Findings for An Global Comparative Observational Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis (NCT NCT01543503)

Last Updated: 2016-02-10

Results Overview

Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker \[erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/h), or C-reactive protein (CRP) in milligram/liter (mg/L)\]. For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of less than or equal to (\</=) 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity.

Recruitment status

COMPLETED

Target enrollment

1225 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2016-02-10

Participant Flow

This observational study was conducted at 158 sites in 16 countries from 9 February 2012 to 20 February 2015.

A total of 1250 participants were screened for entry into the study, with 1225 participants enrolled in the study. One participant whose randomization status was unknown withdrew informed consent.

Participant milestones

Participant milestones
Measure	Tocilizumab Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Overall Study STARTED	426	798
Overall Study COMPLETED	350	711
Overall Study NOT COMPLETED	76	87

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Overall Study Lost to Follow-up	32	36
Overall Study Adverse Event	9	13
Overall Study Lack of Efficacy	4	16
Overall Study Participant withdrew informed consent	8	10
Overall Study Change of jobs	0	1
Overall Study Intolerance to the biologic treatment	0	1
Overall Study Probable overlap of RA with fibromyalgia	1	0
Overall Study Participant did not complete last visit	0	2
Overall Study Refused to continue treatment	7	0
Overall Study Incorrect medication received	1	0
Overall Study Participant moved to another city	2	0
Overall Study Participant will not return for visits	0	2
Overall Study Participant transferred to another city	1	0
Overall Study Participant moved to Scotland	1	0
Overall Study Participant decision to stop treatment	1	0
Overall Study Investigator did not wish to participate	1	1
Overall Study Participant recruited after closing date	0	1
Overall Study Site stopped participation	5	1
Overall Study Participant did not attend a visit	1	0
Overall Study Moved to other rheumatologic site	0	1
Overall Study Participant consented to another study	0	2
Overall Study Participant went to United States	1	0
Overall Study Screen failure	1	0

Baseline Characteristics

An Global Comparative Observational Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	Total n=1216 Participants Total of all reporting groups
Age, Continuous	54.26 years STANDARD_DEVIATION 12.75 • n=5 Participants	55.16 years STANDARD_DEVIATION 13.05 • n=7 Participants	54.85 years STANDARD_DEVIATION 12.95 • n=5 Participants
Sex: Female, Male Female	351 Participants n=5 Participants	615 Participants n=7 Participants	966 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	178 Participants n=7 Participants	250 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Participants belonging to the safety population who had first biologic administration within 60 days after the last Rheumatoid Arthritis (RA) disease activity assessment were included in the effectiveness analysis population. Data of participants available at the time of the assessment were included in the analysis.

Outcome measures

Outcome measures
Measure	Tocilizumab n=155 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=314 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Calculated Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 24	-2.795 Units on a scale Interval -3.107 to -2.483	-1.945 Units on a scale Interval -2.249 to -1.64

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The effectiveness analysis population was used for analysis. Data of participants available at the time of the assessment were included in the analysis.

Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker (ESR in mm/h, or CRP in mg/L). For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of \</= 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=142 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=282 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 52	-3.015 units on a scale Interval -3.279 to -2.751	-2.105 units on a scale Interval -2.325 to -1.885

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

Blood samples were collected for ESR, which is an acute phase reactant and a measure of inflammation. BL = baseline.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Erythrocyte Sedimentation Rate Change from BL to Week 24, n = 225, 456	-22.732 mm/hr Interval -24.717 to -20.747	-9.502 mm/hr Interval -11.112 to -7.892
Mean Change From Baseline in Erythrocyte Sedimentation Rate Change from BL to Week 52, n = 215, 411	-21.515 mm/hr Interval -23.875 to -19.155	-8.868 mm/hr Interval -10.865 to -6.87

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point

Blood samples were collected for C-reactive protein (CRP). CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in C-reactive Protein Change from BL to Week 24, n = 177, 396	-11.005 mg/L Interval -14.131 to -7.88	-4.333 mg/L Interval -6.859 to -1.807
Mean Change From Baseline in C-reactive Protein Change from BL to Week 52, n = 173, 348	-6.332 mg/L Interval -10.524 to -2.14	-5.216 mg/L Interval -8.711 to -1.722

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

A swollen joint count (SJC) is the most specific clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/ not swollen (0) giving a total possible SJC score of 0 to 28.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Swollen Joint Count Change from BL to Week 24, n = 288, 554	-5.698 Number of swollen joints Interval -6.124 to -5.273	-5.122 Number of swollen joints Interval -5.48 to -4.764
Mean Change From Baseline in Swollen Joint Count Change from BL to Week 52, n = 258, 503	-6.313 Number of swollen joints Interval -6.724 to -5.902	-5.561 Number of swollen joints Interval -5.909 to -5.213

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

A tender joint count (TJC) is the most specific clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Tender Joint Count Change from BL to Week 24, n = 289, 554	-7.922 Number of tender joints Interval -8.593 to -7.251	-7.302 Number of tender joints Interval -7.868 to -6.736
Mean Change From Baseline in Tender Joint Count Change from BL to Week 52, n = 259, 501	-8.421 Number of tender joints Interval -9.122 to -7.72	-7.205 Number of tender joints Interval -7.799 to -6.61

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

Clinical Disease Activity Index (CDAI) was calculated as the sum of the following parameters: SJC + TJC + VAS Patient Global Assessment of Disease Activity + VAS Physician Global Assessment of Disease Activity. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity'. CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Simplified Disease Activity Index (SDAI) was calculated as the sum of the following parameters: SJC +TJC + Patient Global Assessment of Disease Activity + Physician Global Assessment of Disease Activity + CRP. SDAI scores ranged from 0 to 86, with higher scores also indicating increased disease activity.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score CDAI, Change from BL to Week 24, n = 176, 286	-20.251 units on a scale Interval -21.934 to -18.568	-16.776 units on a scale Interval -18.28 to -15.271
Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score CDAI, Change from BL to Week 52, n = 162, 267	-22.846 units on a scale Interval -24.634 to -21.058	-18.246 units on a scale Interval -19.823 to -16.669
Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score SDAI, Change from BL to Week 24, n = 93, 193	-21.394 units on a scale Interval -23.668 to -19.12	-18.164 units on a scale Interval -20.051 to -16.278
Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score SDAI, Change from BL to Week 52, n = 91, 169	-22.294 units on a scale Interval -24.791 to -19.797	-19.048 units on a scale Interval -21.128 to -16.969

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

The Physician's Global Assessment of disease activity was assessed using a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). Change from baseline = scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Physician Global Assessment Score Change from BL to Week 24, n = 183, 300	-35.581 scores on a scale Interval -38.656 to -32.506	-26.551 scores on a scale Interval -29.293 to -23.809
Mean Change From Baseline in Physician Global Assessment Score Change from BL to Week 52, n = 174, 287	-37.359 scores on a scale Interval -40.631 to -34.087	-27.122 scores on a scale Interval -30.042 to -24.202

SECONDARY outcome

Timeframe: Up to Week 52

Population: The safety population included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study.

Events that are clearly consistent with the expected pattern of progression of the underlying disease may contribute to lack of efficacy. Lack of efficacy was one of the reasons for termination of biology therapy. The number of participants showing lack of efficacy to biologic therapy is presented.

Outcome measures

Outcome measures
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Loss of Efficacy or Development of Intolerance to Biologic Therapy	15 participants	106 participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: The safety population was used for analysis.

The proportion of participants who discontinued biologic treatment was compared between tocilizumab-treated and TNF inhibitor-treated participants.

Outcome measures

Outcome measures
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Proportion of Participants Who Terminated Biologic Treatment	14.9 Percentage of participants	27.4 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: The safety population was used for analysis.

The reasons for discontinuation of tocilizumab or TNF inhibitor is presented.

Outcome measures

Outcome measures
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Reasons for Treatment Discontinuation Adverse event	24 participants	87 participants
Reasons for Treatment Discontinuation Lack of efficacy	15 participants	106 participants
Reasons for Treatment Discontinuation Other	24 participants	23 participants

SECONDARY outcome

Timeframe: Up to end of treatment

Population: The safety population was used for analysis.

The total number of participants who discontinued biologic therapy at the end of each study period (Week 0 - 24, Week 24 - 52, Week 52 - 57 and Week 57 - end of treatment) is presented. Participants who did not have a biologic therapy discontinuation or discontinued before having one, were considered as 'censored' at the date study termination.

Outcome measures

Outcome measures
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period Week 52 - 57	62 participants	212 participants
Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period Week 0 -24	36 participants	119 participants
Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period Week 24 - 52	61 participants	208 participants
Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period Week 57 - End of treatment	63 participants	216 participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: The safety population was used for analysis.

An infusion reaction was defined as an adverse event (AE) occurring during and within 24 hours after the infusion, which may include hypersensitivity reactions or anaphylactic reactions. Injection site reactions were included in the summaries for infusion reactions.

Outcome measures

Outcome measures
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy Participants with Non-Serious infusion reaction	33 participants	75 participants
Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy Participants with Serious infusion reaction	4 participants	3 participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: The safety population was used for analysis.

An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events Participants with AE	208 participants	449 participants
Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events Participants with SAE	22 participants	64 participants
Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events Participants with non-serious AE	196 participants	421 participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: The safety population was used for analysis.

Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events. Based on seriousness criteria, they were categorized as serious and non-serious adverse events of special interest.

Outcome measures

Outcome measures
Measure	Tocilizumab n=423 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study Participants with Serious AESI	13 participants	27 participants
Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study Participants with Non-Serious AESI	22 participants	16 participants

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score Change from BL to Week 24, n = 169, 301	-0.591 Scores on a scale Interval -0.694 to -0.488	-0.445 Scores on a scale Interval -0.538 to -0.352
Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score Change from BL to Week 52, n = 152, 255	-0.593 Scores on a scale Interval -0.71 to -0.476	-0.430 Scores on a scale Interval -0.539 to -0.32

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score Change from BL to Week 24, n = 64, 86	-7.153 scores on a scale Interval -10.003 to -4.304	-3.260 scores on a scale Interval -6.279 to -0.242
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score Change from BL to Week 52, n = 50, 77	-4.566 scores on a scale Interval -7.822 to -1.31	-1.779 scores on a scale Interval -5.096 to 1.538

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.

VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change from baseline =scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Mean Change From Baseline in Visual Analogue Scale Pain Score Change from BL to Week 24, n = 204, 378	-29.308 units on a scale Interval -32.922 to -25.694	-23.647 units on a scale Interval -26.664 to -20.63
Mean Change From Baseline in Visual Analogue Scale Pain Score Change from BL to Week 52, n = 183, 336	-32.957 units on a scale Interval -36.711 to -29.202	-23.155 units on a scale Interval -26.386 to -19.923

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis.

Shift tables presenting the number of participants in each bivariate category Week (W) 0 versus Week 24 and Week 52, with regards to morning stiffness at the different time points, was presented for each treatment arm. For participants who experienced joint stiffness while waking up in the morning, duration of morning stiffness was categorized as follows: Less than 30 minutes (min), Between 30 and 60 minutes, Between 60 and 120 minutes, Between 120 to 240 minutes, More than 240 minutes and the whole day. Baseline = BL

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Shift From Baseline in Morning Stiffness BL, the whole day; W 24, > 240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 24, the whole day	1 participants	1 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 52, < 30 min	6 participants	13 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 52, 30-60 min	2 participants	4 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 52, 60-120 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 52, 120-240 min	2 participants	1 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 52, > 240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 24, < 30 min	13 participants	19 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 24, 30-60 min	1 participants	8 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 24, 60-120 min	2 participants	1 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 24, 120-240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 24, > 240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 24, the whole day	1 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 24 < 30 min	19 participants	49 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 24, 30-60 min	9 participants	30 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 24, 60-120 min	1 participants	3 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 24, 120-240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 24, > 240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 24, the whole day	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 24, < 30 min	22 participants	34 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 24, 30-60 min	17 participants	22 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 24, 60-120 min	4 participants	7 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 24, 120-240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 24, > 240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 24, the whole day	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 24, < 30 min	12 participants	10 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 24, 30-60 min	6 participants	9 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 24, 60-120 min	2 participants	8 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 24, 120-240 min	3 participants	4 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 24, > 240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 24, the whole day	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 24, < 30 min	0 participants	7 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 24, 30-60 min	2 participants	2 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 24, 60-120 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 24, 120-240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 24, > 240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 24, the whole day	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 24, < 30 min	1 participants	2 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 24, 30-60 min	3 participants	2 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 24, 60-120 min	2 participants	5 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 24, 120-240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, < 30 min; W 52, the whole day	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 52, < 30 min	17 participants	43 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 52, 30-60 min	9 participants	19 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 52, 60-120 min	1 participants	5 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 52, 120-240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 52, > 240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 30-60 min; W 52, the whole day	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 52, < 30 min	20 participants	33 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 52, 30-60 min	8 participants	21 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 52, 60-120 min	4 participants	4 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 52, 120-240 min	0 participants	3 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 52, > 240 min	0 participants	2 participants
Shift From Baseline in Morning Stiffness BL, between 60-120 min; W 52, the whole day	1 participants	0 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 52, < 30 min	14 participants	9 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 52, 30-60 min	6 participants	6 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 52, 60-120 min	5 participants	8 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 52, 120-240 min	1 participants	3 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 52, > 240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, between 120-240 min; W 52, the whole day	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 52, < 30 min	0 participants	5 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 52, 30-60 min	2 participants	4 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 52, 60-120 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 52, 120-240 min	1 participants	0 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 52, > 240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, more than 240 min; W 52, the whole day	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 52, < 30 min	2 participants	3 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 52, 30-60 min	1 participants	2 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 52, 60-120 min	2 participants	2 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 52, 120-240 min	0 participants	1 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 52, > 240 min	0 participants	0 participants
Shift From Baseline in Morning Stiffness BL, the whole day; W 52, the whole day	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point

The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Tocilizumab n=390 Participants Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=693 Participants Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Change From Baseline in Patient Global Assessment of Disease Activity Change from BL to Week 24, n = 225, 423	-29.633 scores on a scale Interval -32.994 to -26.273	-24.525 scores on a scale Interval -27.388 to -21.662
Change From Baseline in Patient Global Assessment of Disease Activity Change from BL to Week 52, n = 206, 378	-31.919 scores on a scale Interval -35.63 to -28.209	-24.153 scores on a scale Interval -27.385 to -20.921

Adverse Events

Tocilizumab

Serious events: 22 serious events

Other events: 132 other events

Deaths: 0 deaths

TNF Inhibitor

Serious events: 64 serious events

Other events: 231 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

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

Measure	Tocilizumab n=423 participants at risk Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.	TNF Inhibitor n=793 participants at risk Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks.
Blood and lymphatic system disorders NEUTROPENIA	3.3% 14/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	0.38% 3/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Gastrointestinal disorders DIARRHOEA	0.95% 4/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.1% 9/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Gastrointestinal disorders NAUSEA	2.1% 9/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.9% 15/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
General disorders INJECTION SITE REACTION	0.24% 1/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	2.8% 22/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations BRONCHITIS	2.6% 11/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.6% 13/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations CELLULITIS	0.47% 2/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.0% 8/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations HERPES ZOSTER	0.95% 4/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.0% 8/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	3.5% 15/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	4.4% 35/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations NASOPHARYNGITIS	3.1% 13/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	2.3% 18/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations PHARYNGITIS	1.2% 5/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	0.50% 4/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations RESPIRATORY TRACT INFECTION	1.2% 5/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.3% 10/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations SINUSITIS	1.4% 6/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.0% 8/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Infections and infestations URINARY TRACT INFECTION	3.5% 15/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	3.3% 26/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Investigations ALANINE AMINOTRANSFERASE INCREASED	1.9% 8/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.6% 13/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Investigations NEUTROPHIL COUNT DECREASED	1.2% 5/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.0% 8/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Investigations TRANSAMINASES INCREASED	2.4% 10/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	0.50% 4/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Metabolism and nutrition disorders HYPERCHOLESTEROLAEMIA	2.1% 9/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	0.63% 5/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Metabolism and nutrition disorders HYPERTRIGLYCERIDAEMIA	2.4% 10/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	0.88% 7/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Musculoskeletal and connective tissue disorders BACK PAIN	0.95% 4/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.4% 11/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Nervous system disorders HEADACHE	1.7% 7/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	2.9% 23/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Respiratory, thoracic and mediastinal disorders COUGH	2.4% 10/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.5% 12/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.71% 3/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.1% 9/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Skin and subcutaneous tissue disorders ALOPECIA	0.95% 4/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.0% 8/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Skin and subcutaneous tissue disorders PRURITUS	0.24% 1/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	1.0% 8/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.
Skin and subcutaneous tissue disorders RASH	2.1% 9/423 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.	2.9% 23/793 • Up to Week 52 SAEs and non-serious AEs were reported for members of the safety population, which included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study. All SAEs are reported, without any frequency threshold.