Trial Outcomes & Findings for A Long-Term Extension Study of WA22762 and NA25220 of Subcutaneous (SC) Tocilizumab (TCZ) in Moderate to Severe Rheumatoid Arthritis (RA) (NCT NCT01662063)

Results Overview

Adverse events (AEs) were monitored throughout treatment. AEs were defined as any untoward medical occurrence in a participant who received study drug regardless of causality. SAEs were defined as AEs that were fatal or life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, manifested as a congenital anomaly/birth defect, were medically significant, or required intervention to prevent any of the aforementioned outcomes. The number of participants with at least one SAE regardless of treatment relationship was reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

218 participants

Primary outcome timeframe

From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall)

Results posted on

2016-10-12

Participant Flow

Participant milestones

Participant milestones
Measure	Subcutaneous (SC) Tocilizumab (TCZ) Every 2 Weeks (Q2W) Participants with moderate to severe rheumatoid arthritis (RA) who completed treatment with SC or intravenous (IV) TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this long-term extension (LTE) study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 milligrams (mg) Q2W.	SC TCZ Every Week (QW) Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.	Not Treated Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) were enrolled in this LTE study for an additional 96 weeks. Participants who met Screening criteria but did not receive treatment were excluded from analysis and reported in a separate arm.
Overall Study STARTED	44	173	1
Overall Study COMPLETED	39	144	0
Overall Study NOT COMPLETED	5	29	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Subcutaneous (SC) Tocilizumab (TCZ) Every 2 Weeks (Q2W) Participants with moderate to severe rheumatoid arthritis (RA) who completed treatment with SC or intravenous (IV) TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this long-term extension (LTE) study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 milligrams (mg) Q2W.	SC TCZ Every Week (QW) Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.	Not Treated Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) were enrolled in this LTE study for an additional 96 weeks. Participants who met Screening criteria but did not receive treatment were excluded from analysis and reported in a separate arm.
Overall Study Adverse Event or Intercurrent Illness	1	12	0
Overall Study Lack of Efficacy	1	6	0
Overall Study Lost to Follow-up	0	4	0
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	2	4	1
Overall Study Physician Decision	0	2	0
Overall Study Other	0	1	0

Baseline Characteristics

A Long-Term Extension Study of WA22762 and NA25220 of Subcutaneous (SC) Tocilizumab (TCZ) in Moderate to Severe Rheumatoid Arthritis (RA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.	Total n=217 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 10.18 • n=5 Participants	58.1 years STANDARD_DEVIATION 10.38 • n=7 Participants	58.4 years STANDARD_DEVIATION 10.33 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	133 Participants n=7 Participants	166 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	40 Participants n=7 Participants	51 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall)

Population: Safety Population.

Adverse events (AEs) were monitored throughout treatment. AEs were defined as any untoward medical occurrence in a participant who received study drug regardless of causality. SAEs were defined as AEs that were fatal or life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, manifested as a congenital anomaly/birth defect, were medically significant, or required intervention to prevent any of the aforementioned outcomes. The number of participants with at least one SAE regardless of treatment relationship was reported.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Number of Participants With at Least One Serious Adverse Event (SAE)	4 participants	19 participants

PRIMARY outcome

Timeframe: From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall)

Population: Safety Population.

AEs were monitored throughout treatment. AEs were defined as any untoward medical occurrence in a participant who received study drug regardless of causality. SAEs were defined as AEs that were fatal or life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, manifested as a congenital anomaly/birth defect, were medically significant, or required intervention to prevent any of the aforementioned outcomes. The percentage of participants with at least one SAE regardless of treatment relationship was calculated.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With at Least One SAE	9.1 percentage of participants	11.0 percentage of participants

PRIMARY outcome

Timeframe: From Baseline to 8 weeks after last dose; assessed at Baseline; Weeks 12, 24, 36, 48, 60, 72, 84, 96; and up to 8 weeks after last dose (up to 2 years overall)

Population: Safety Population; only participants with a valid assay at Screening were included.

Blood samples were collected to test for the presence of antibodies to TCZ. The percentage of participants with a positive anti-TCZ antibody assay was calculated.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=166 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With a Positive Anti-TCZ Antibody Assay at Any Timepoint	4.5 percentage of participants	7.8 percentage of participants

PRIMARY outcome

Timeframe: Baseline

Population: Safety Population; only participants with a valid assay at Screening were included.

Blood samples were collected to test for the presence of antibodies to TCZ. The percentage of participants with a positive anti-TCZ antibody assay was calculated.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=166 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With a Positive Anti-TCZ Antibody Assay at Baseline	2.3 percentage of participants	4.8 percentage of participants

PRIMARY outcome

Timeframe: From Week 12 up to 8 weeks after last dose; assessed at Weeks 12, 24, 36, 48, 60, 72, 84, 96; and up to 8 weeks after last dose (up to 2 years overall)

Population: Safety Population; only participants with a valid assay at Screening were included.

Blood samples were collected to test for the presence of antibodies to TCZ. The percentage of participants with a positive anti-TCZ antibody assay was calculated. Positive assay results obtained post-Baseline were further investigated via confirmation assay and a neutralization assay.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=166 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With a Positive Anti-TCZ Antibody Assay Post-Baseline Positive Confirmation Assay	0 percentage of participants	0.6 percentage of participants
Percentage of Participants With a Positive Anti-TCZ Antibody Assay Post-Baseline Positive Anti-TCZ Assay	2.3 percentage of participants	3.0 percentage of participants
Percentage of Participants With a Positive Anti-TCZ Antibody Assay Post-Baseline Positive Neutralizing Assay	0 percentage of participants	0.6 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: Intent-to-Treat (ITT) Population: All participants who received at least one dose of study medication and had at least one post-dose efficacy assessment.

Compliance was assessed using drug dispensing logs, diary cards kept by the participant, and return records, as reviewed by the Investigator at regular visits. Total compliance up to the end of treatment was defined as the percentage of participants who correctly administered all scheduled doses of SC TCZ. Correct administration was defined as proper injection technique, injection of the correct amount (162 mg), device not left at room temperature for greater than (\>) 8 hours, and absence of other medication errors.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants Who Correctly Administered All SC TCZ Doses	97.7 percentage of participants	97.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The DAS28 was calculated using the Swollen Joint Count (SJC), Tender Joint Count (TJC), erythrocyte sedimentation rate (ESR), and Global Assessment of Disease Activity by the participant according to Visual Analog Scale (VAS) score. For the DAS28 formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-millimeter (mm) scale to a 10-point score. The DAS28 was calculated as (0.56 multiplied by \[×\] square root of TJC) + (0.28 × square root of SJC) + (0.7 × log natural \[ln\] ESR) + (0.014 × VAS). Scores may range from 0 to 10, where higher scores indicate increased disease activity.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Disease Activity Score Based on 28 Joints (DAS28) Score Week 72 (n=1,52)	5.76 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	3.05 units on a scale Standard Deviation 1.970
Disease Activity Score Based on 28 Joints (DAS28) Score Week 84 (n=0,11)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis.	2.78 units on a scale Standard Deviation 1.434
Disease Activity Score Based on 28 Joints (DAS28) Score Baseline (n=44,172)	4.55 units on a scale Standard Deviation 1.732	4.60 units on a scale Standard Deviation 1.869
Disease Activity Score Based on 28 Joints (DAS28) Score Week 12 (n=44,172)	3.17 units on a scale Standard Deviation 1.443	3.42 units on a scale Standard Deviation 1.728
Disease Activity Score Based on 28 Joints (DAS28) Score Week 24 (n=43,168)	3.08 units on a scale Standard Deviation 1.351	3.35 units on a scale Standard Deviation 1.786
Disease Activity Score Based on 28 Joints (DAS28) Score Week 36 (n=39,159)	3.07 units on a scale Standard Deviation 1.425	3.29 units on a scale Standard Deviation 1.624
Disease Activity Score Based on 28 Joints (DAS28) Score Week 48 (n=18,141)	3.15 units on a scale Standard Deviation 1.392	3.25 units on a scale Standard Deviation 1.639
Disease Activity Score Based on 28 Joints (DAS28) Score Week 60 (n=2,92)	4.10 units on a scale Standard Deviation 0.515	3.12 units on a scale Standard Deviation 1.626

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The DAS28 was calculated using the SJC, TJC, ESR, and Global Assessment of Disease Activity by the participant according to VAS score. For the DAS28 formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The DAS28 was calculated as (0.56 × square root of TJC) + (0.28 × square root of SJC) + (0.7 × ln ESR) + (0.014 × VAS). Scores may range from 0 to 10, where higher scores indicate increased disease activity. The change from Baseline to each visit was calculated, where positive changes represent an increase or worsening in disease activity.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=172 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in DAS28 Score Week 12 (n=44,171)	-1.38 units on a scale Standard Deviation 1.522	-1.19 units on a scale Standard Deviation 1.415
Change From Baseline in DAS28 Score Week 24 (n=43,167)	-1.42 units on a scale Standard Deviation 1.383	-1.23 units on a scale Standard Deviation 1.692
Change From Baseline in DAS28 Score Week 84 (n=0,10)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis.	-1.57 units on a scale Standard Deviation 1.312
Change From Baseline in DAS28 Score Week 36 (n=39,158)	-1.51 units on a scale Standard Deviation 1.312	-1.29 units on a scale Standard Deviation 1.429
Change From Baseline in DAS28 Score Week 48 (n=18,140)	-1.66 units on a scale Standard Deviation 1.340	-1.32 units on a scale Standard Deviation 1.538
Change From Baseline in DAS28 Score Week 60 (n=2,91)	0.65 units on a scale Standard Deviation 1.410	-1.29 units on a scale Standard Deviation 1.286
Change From Baseline in DAS28 Score Week 72 (n=1,52)	-0.35 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-1.53 units on a scale Standard Deviation 1.435

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

The CDAI was calculated using the SJC, TJC, and Global Assessment of Disease Activity by the patient and by the physician according to separate VAS scores. For the CDAI formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The CDAI was calculated as the sum of the component scores, that is, SJC + TJC + VAS (participant) + VAS (physician). Scores may range from 0 to 76, where higher scores indicate increased disease activity.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Clinical Disease Activity Index (CDAI) Score Baseline (n=44,173)	20.10 units on a scale Standard Deviation 15.467	23.91 units on a scale Standard Deviation 16.346
Clinical Disease Activity Index (CDAI) Score Week 12 (n=44,172)	13.99 units on a scale Standard Deviation 13.058	18.19 units on a scale Standard Deviation 14.145
Clinical Disease Activity Index (CDAI) Score Week 24 (n=42,166)	14.86 units on a scale Standard Deviation 13.232	18.03 units on a scale Standard Deviation 13.665
Clinical Disease Activity Index (CDAI) Score Week 36 (n=39,159)	13.26 units on a scale Standard Deviation 11.839	16.92 units on a scale Standard Deviation 12.598
Clinical Disease Activity Index (CDAI) Score Week 48 (n=18,140)	15.81 units on a scale Standard Deviation 16.479	16.55 units on a scale Standard Deviation 13.559
Clinical Disease Activity Index (CDAI) Score Week 60 (n=2,92)	13.60 units on a scale Standard Deviation 2.828	14.71 units on a scale Standard Deviation 11.954
Clinical Disease Activity Index (CDAI) Score Week 72 (n=1,52)	27.80 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	16.04 units on a scale Standard Deviation 15.476
Clinical Disease Activity Index (CDAI) Score Week 84 (n=0,11)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis	12.82 units on a scale Standard Deviation 9.154

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The CDAI was calculated using the SJC, TJC, and Global Assessment of Disease Activity by the patient and by the physician according to separate VAS scores. For the CDAI formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The CDAI was calculated as the sum of the component scores, that is, SJC + TJC + VAS (participant) + VAS (physician). Scores may range from 0 to 76, where higher scores indicate increased disease activity. The change from Baseline to each visit was calculated, where positive changes represent an increase or worsening in disease activity.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in CDAI Score Week 24 (n=42,166)	-5.23 units on a scale Standard Deviation 14.134	-5.47 units on a scale Standard Deviation 13.754
Change From Baseline in CDAI Score Week 36 (n=39,159)	-7.00 units on a scale Standard Deviation 12.266	-6.63 units on a scale Standard Deviation 10.676
Change From Baseline in CDAI Score Week 12 (n=44,172)	-6.11 units on a scale Standard Deviation 13.219	-5.81 units on a scale Standard Deviation 12.010
Change From Baseline in CDAI Score Week 48 (n=18,140)	-6.63 units on a scale Standard Deviation 13.479	-6.70 units on a scale Standard Deviation 12.328
Change From Baseline in CDAI Score Week 60 (n=2,92)	-14.05 units on a scale Standard Deviation 20.294	-7.05 units on a scale Standard Deviation 11.065
Change From Baseline in CDAI Score Week 72 (n=1,52)	-16.20 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-6.31 units on a scale Standard Deviation 12.999
Change From Baseline in CDAI Score Week 84 (n=0,11)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis	-10.01 units on a scale Standard Deviation 18.580

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The SDAI was calculated using the SJC, TJC, Global Assessment of Disease Activity by the patient and by the physician according to separate VAS scores, and high-sensitivity C-reactive protein (hsCRP) level. For the SDAI formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The SDAI was calculated as the sum of the component scores, that is, SJC + TJC + VAS (participant) + VAS (physician) + hsCRP. Because the formula includes hsCRP, scores may theoretically range from 0 to infinity, where higher scores indicate increased disease activity. However, based upon normal hsCRP level within 1 milligram per deciliter (mg/dL), scores would be expected to fall within less than or equal to (≤) 77 points.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Simplified Disease Activity Index (SDAI) Score Week 36 (n=39,159)	13.75 units on a scale Standard Deviation 11.841	17.06 units on a scale Standard Deviation 12.621
Simplified Disease Activity Index (SDAI) Score Week 48 (n=18,140)	15.85 units on a scale Standard Deviation 16.490	16.76 units on a scale Standard Deviation 13.603
Simplified Disease Activity Index (SDAI) Score Week 60 (n=2,92)	13.63 units on a scale Standard Deviation 2.841	14.90 units on a scale Standard Deviation 12.045
Simplified Disease Activity Index (SDAI) Score Week 72 (n=1,52)	27.82 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	16.23 units on a scale Standard Deviation 15.730
Simplified Disease Activity Index (SDAI) Score Week 84 (n=0,11)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis	12.90 units on a scale Standard Deviation 9.163
Simplified Disease Activity Index (SDAI) Score Baseline (n=44,170)	21.54 units on a scale Standard Deviation 15.717	25.10 units on a scale Standard Deviation 16.972
Simplified Disease Activity Index (SDAI) Score Week 12 (n=44,172)	14.48 units on a scale Standard Deviation 13.058	18.32 units on a scale Standard Deviation 14.199
Simplified Disease Activity Index (SDAI) Score Week 24 (n=41,166)	15.42 units on a scale Standard Deviation 13.266	18.18 units on a scale Standard Deviation 13.779

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The SDAI was calculated using the SJC, TJC, Global Assessment of Disease Activity by the patient and by the physician according to separate VAS scores, and hsCRP level. For the SDAI formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The SDAI was calculated as the sum of the component scores, that is, SJC + TJC + VAS (participant) + VAS (physician) + hsCRP. Because the formula includes hsCRP, scores may theoretically range from 0 to infinity, where higher scores indicate increased disease activity. However, based upon normal hsCRP level within 1 mg/dL, scores would be expected to fall within ≤77 points. The change from Baseline to each visit was calculated, where positive changes represent an increase or worsening in disease activity.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=170 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in SDAI Score Week 12 (n=44,169)	-7.07 units on a scale Standard Deviation 13.671	-7.00 units on a scale Standard Deviation 12.056
Change From Baseline in SDAI Score Week 24 (n=41,163)	-5.71 units on a scale Standard Deviation 14.217	-6.79 units on a scale Standard Deviation 13.069
Change From Baseline in SDAI Score Week 36 (n=39,157)	-7.99 units on a scale Standard Deviation 12.858	-7.38 units on a scale Standard Deviation 10.953
Change From Baseline in SDAI Score Week 48 (n=18,139)	-8.17 units on a scale Standard Deviation 14.640	-7.29 units on a scale Standard Deviation 12.454
Change From Baseline in SDAI Score Week 60 (n=2,91)	-14.46 units on a scale Standard Deviation 20.873	-7.52 units on a scale Standard Deviation 10.846
Change From Baseline in SDAI Score Week 72 (n=1,52)	-17.04 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-7.10 units on a scale Standard Deviation 13.379
Change From Baseline in SDAI Score Week 84 (n=0,10)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis	-9.48 units on a scale Standard Deviation 19.290

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

Sixty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination. The number of tender joints was taken as the TJC score, where values may range from 0 to 68.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Tender Joint Count (TJC) Score Week 12 (n=44,172)	9.86 tender joints Standard Deviation 11.727	14.06 tender joints Standard Deviation 14.874
Tender Joint Count (TJC) Score Week 24 (n=42,167)	10.95 tender joints Standard Deviation 14.221	13.86 tender joints Standard Deviation 15.176
Tender Joint Count (TJC) Score Week 36 (n=39,159)	9.10 tender joints Standard Deviation 11.392	13.45 tender joints Standard Deviation 14.398
Tender Joint Count (TJC) Score Week 48 (n=18,141)	10.61 tender joints Standard Deviation 14.825	12.85 tender joints Standard Deviation 16.192
Tender Joint Count (TJC) Score Week 60 (n=2,92)	5.50 tender joints Standard Deviation 0.707	10.47 tender joints Standard Deviation 12.589
Tender Joint Count (TJC) Score Week 72 (n=1,52)	21.00 tender joints Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	11.38 tender joints Standard Deviation 15.444
Tender Joint Count (TJC) Score Week 84 (n=0,11)	NA tender joints Standard Deviation NA No participants provided evaluable data for the analysis	9.36 tender joints Standard Deviation 10.984
Tender Joint Count (TJC) Score Baseline (n=44,173)	13.84 tender joints Standard Deviation 13.883	19.14 tender joints Standard Deviation 18.469

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

Sixty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination. The number of tender joints was taken as the TJC score, where values may range from 0 to 68. The change from Baseline to each visit was calculated, where positive changes represent an increase in number of tender joints.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in TJC Score Week 36 (n=39,159)	-4.03 tender joints Standard Deviation 10.559	-5.60 tender joints Standard Deviation 12.402
Change From Baseline in TJC Score Week 48 (n=18,141)	-4.00 tender joints Standard Deviation 12.902	-5.95 tender joints Standard Deviation 13.899
Change From Baseline in TJC Score Week 60 (n=2,92)	-9.00 tender joints Standard Deviation 12.728	-6.23 tender joints Standard Deviation 10.672
Change From Baseline in TJC Score Week 72 (n=1,52)	-3.00 tender joints Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-4.98 tender joints Standard Deviation 11.514
Change From Baseline in TJC Score Week 84 (n=0,11)	NA tender joints Standard Deviation NA No participants provided evaluable data for the analysis	-6.27 tender joints Standard Deviation 13.835
Change From Baseline in TJC Score Week 12 (n=44,172)	-3.98 tender joints Standard Deviation 12.082	-5.17 tender joints Standard Deviation 12.175
Change From Baseline in TJC Score Week 24 (n=42,167)	-2.69 tender joints Standard Deviation 12.546	-5.12 tender joints Standard Deviation 14.817

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

Sixty-six joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination. The number of swollen joints was taken as the SJC score, where values may range from 0 to 66.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Swollen Joint Count (SJC) Score Baseline (n=44,173)	9.07 swollen joints Standard Deviation 8.877	10.83 swollen joints Standard Deviation 10.855
Swollen Joint Count (SJC) Score Week 12 (n=44,172)	5.61 swollen joints Standard Deviation 7.144	7.87 swollen joints Standard Deviation 8.839
Swollen Joint Count (SJC) Score Week 24 (n=42,167)	5.98 swollen joints Standard Deviation 8.587	8.57 swollen joints Standard Deviation 8.783
Swollen Joint Count (SJC) Score Week 48 (n=18,141)	4.78 swollen joints Standard Deviation 9.078	7.23 swollen joints Standard Deviation 7.870
Swollen Joint Count (SJC) Score Week 60 (n=2,92)	2.00 swollen joints Standard Deviation 2.828	6.52 swollen joints Standard Deviation 7.184
Swollen Joint Count (SJC) Score Week 72 (n=1,52)	2.00 swollen joints Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	7.98 swollen joints Standard Deviation 8.873
Swollen Joint Count (SJC) Score Week 36 (n=39,159)	5.51 swollen joints Standard Deviation 8.398	6.92 swollen joints Standard Deviation 7.055
Swollen Joint Count (SJC) Score Week 84 (n=0,11)	NA swollen joints Standard Deviation NA No participants provided evaluable data for the analysis	8.64 swollen joints Standard Deviation 8.857

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

Sixty-six joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination. The number of swollen joints was taken as the SJC score, where values may range from 0 to 66. The change from Baseline to each visit was calculated, where positive changes represent an increase in number of swollen joints.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in SJC Score Week 12 (n=44,172)	-3.45 swollen joints Standard Deviation 7.026	-3.00 swollen joints Standard Deviation 8.543
Change From Baseline in SJC Score Week 24 (n=42,167)	-3.45 swollen joints Standard Deviation 8.434	-2.31 swollen joints Standard Deviation 9.162
Change From Baseline in SJC Score Week 36 (n=39,159)	-3.33 swollen joints Standard Deviation 6.868	-3.89 swollen joints Standard Deviation 8.134
Change From Baseline in SJC Score Week 48 (n=18,141)	-6.56 swollen joints Standard Deviation 9.332	-3.25 swollen joints Standard Deviation 9.543
Change From Baseline in SJC Score Week 60 (n=2,92)	-8.50 swollen joints Standard Deviation 12.021	-3.20 swollen joints Standard Deviation 8.702
Change From Baseline in SJC Score Week 72 (n=1,52)	-15.00 swollen joints Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-1.15 swollen joints Standard Deviation 10.114
Change From Baseline in SJC Score Week 84 (n=0,11)	NA swollen joints Standard Deviation NA No participants provided evaluable data for the analysis	-2.64 swollen joints Standard Deviation 13.493

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants receiving at least one DMARD at Baseline were included.

Use of concomitant medications, including non-biologic DMARDs, was recorded throughout the study. Any change in DMARD therapy was documented and reported among those participants receiving at least one DMARD at Baseline.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=41 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=161 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation Any Dose Reduction/Interruption/Discontinuation	3 participants	37 participants
Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation Dose Reduction	1 participants	14 participants
Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation Discontinuation >60 Days	2 participants	15 participants
Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation Dose Interruption ≤60 Days	1 participants	15 participants
Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation Dose Reduction/Interruption ≤60 Days	1 participants	27 participants

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants receiving at least one DMARD at Baseline were included.

Use of concomitant medications, including non-biologic DMARDs, was recorded throughout the study. Any change in DMARD therapy was documented and reported among those participants receiving at least one DMARD at Baseline.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=41 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=161 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation Discontinuation >60 Days	4.9 percentage of participants	9.3 percentage of participants
Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation Any Dose Reduction/Interruption/Discontinuation	7.3 percentage of participants	23.0 percentage of participants
Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation Dose Reduction	2.4 percentage of participants	8.7 percentage of participants
Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation Dose Interruption ≤60 Days	2.4 percentage of participants	9.3 percentage of participants
Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation Dose Reduction/Interruption ≤60 Days	2.4 percentage of participants	16.8 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants with a DMARD dose reduction/interruption ≤60 days were included.

Use of concomitant medications, including non-biologic DMARDs, was recorded throughout the study. Any change in DMARD therapy was documented and reported among those participants receiving at least one DMARD at Baseline. The reasons for any DMARD dose reduction/interruption ≤60 days were reported. More than one reason could be given for a single change in DMARD therapy, and each participant could also change DMARD therapy more than once. Therefore, the number of reasons could exceed the number of participants analyzed.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=2 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=41 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Reasons Given for DMARD Dose Reduction or Interruption AEs	0 percentage of reasons	70.7 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption Efficacy	0 percentage of reasons	2.4 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption Joint Surgery	0 percentage of reasons	2.4 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption Medical History	100.0 percentage of reasons	2.4 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption RA Improvement	0 percentage of reasons	7.3 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption RA Treatment	0 percentage of reasons	2.4 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption Replace Previous Drug	0 percentage of reasons	2.4 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption Participant Request	0 percentage of reasons	2.4 percentage of reasons
Percentage of Reasons Given for DMARD Dose Reduction or Interruption Not Specified	0 percentage of reasons	7.3 percentage of reasons

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants with a DMARD discontinuation \>60 days were included.

Use of concomitant medications, including non-biologic DMARDs, was recorded throughout the study. Any change in DMARD therapy was documented and reported among those participants receiving at least one DMARD at Baseline. The reasons for any DMARD discontinuation were reported. More than one reason could be given for a single change in DMARD therapy, and each participant could also change DMARD therapy more than once. Therefore, the number of reasons could exceed the number of participants analyzed.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=3 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=16 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Reasons Given for DMARD Discontinuation Efficacy	33.3 percentage of reasons	0 percentage of reasons
Percentage of Reasons Given for DMARD Discontinuation AEs	66.7 percentage of reasons	43.8 percentage of reasons
Percentage of Reasons Given for DMARD Discontinuation Investigator Recommendation	0 percentage of reasons	6.3 percentage of reasons
Percentage of Reasons Given for DMARD Discontinuation Participant Request	0 percentage of reasons	6.3 percentage of reasons
Percentage of Reasons Given for DMARD Discontinuation Not Specified	0 percentage of reasons	6.3 percentage of reasons
Percentage of Reasons Given for DMARD Discontinuation RA Improvement	0 percentage of reasons	31.3 percentage of reasons
Percentage of Reasons Given for DMARD Discontinuation Too Expensive	0 percentage of reasons	6.3 percentage of reasons

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants who received at least one CCS before the last dose of TCZ were included.

Use of concomitant medications, including CCS treatment, was recorded throughout the study. Any change in CCS therapy was documented and reported among those participants who received at least one CCS before the last dose of SC TCZ.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=15 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=89 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Number of Participants With a Corticosteroid (CCS) Dose Reduction, Interruption, or Discontinuation Any Dose Reduction/Interruption/Discontinuation	6 participants	33 participants
Number of Participants With a Corticosteroid (CCS) Dose Reduction, Interruption, or Discontinuation Dose Reduction	5 participants	24 participants
Number of Participants With a Corticosteroid (CCS) Dose Reduction, Interruption, or Discontinuation Dose Interruption ≤14 Days	0 participants	2 participants
Number of Participants With a Corticosteroid (CCS) Dose Reduction, Interruption, or Discontinuation Discontinuation >14 Days	2 participants	19 participants

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants who received at least one CCS before the last dose of TCZ were included.

Use of concomitant medications, including CCS treatment, was recorded throughout the study. Any change in CCS therapy was documented and reported among those participants who received at least one CCS before the last dose of SC TCZ.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=15 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=89 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With a CCS Dose Reduction, Interruption, or Discontinuation Any Dose Reduction/Interruption/Discontinuation	40.0 percentage of participants	37.1 percentage of participants
Percentage of Participants With a CCS Dose Reduction, Interruption, or Discontinuation Dose Reduction	33.3 percentage of participants	27.0 percentage of participants
Percentage of Participants With a CCS Dose Reduction, Interruption, or Discontinuation Dose Interruption ≤14 Days	0 percentage of participants	2.2 percentage of participants
Percentage of Participants With a CCS Dose Reduction, Interruption, or Discontinuation Discontinuation >14 Days	13.3 percentage of participants	21.3 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants with a CCS dose reduction were included.

Use of concomitant medications, including CCS treatment, was recorded throughout the study. Any change in CCS therapy was documented and reported among those participants who received at least one CCS before the last dose of SC TCZ. The reasons for any CCS dose reduction were reported. More than one reason could be given for a single change in CCS therapy, and each participant could also change CCS therapy more than once. Therefore, the number of reasons could exceed the number of participants analyzed.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=14 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=84 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Reasons Given for CCS Dose Reduction AEs	0 percentage of reasons	3.6 percentage of reasons
Percentage of Reasons Given for CCS Dose Reduction Medical History	42.9 percentage of reasons	0 percentage of reasons
Percentage of Reasons Given for CCS Dose Reduction RA Treatment	0 percentage of reasons	2.4 percentage of reasons
Percentage of Reasons Given for CCS Dose Reduction Participant Request	0 percentage of reasons	1.2 percentage of reasons
Percentage of Reasons Given for CCS Dose Reduction Not Specified	7.1 percentage of reasons	1.2 percentage of reasons
Percentage of Reasons Given for CCS Dose Reduction Steroid Tapering	50.0 percentage of reasons	91.7 percentage of reasons

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants with a CCS dose interruption ≤14 days were included. Results were only reported for the QW arm because no participants in the Q2W arm had a CCS dose interruption.

Use of concomitant medications, including CCS treatment, was recorded throughout the study. Any change in CCS therapy was documented and reported among those participants who received at least one CCS before the last dose of SC TCZ. The reasons for any CCS dose interruption ≤14 days were reported. More than one reason could be given for a single change in CCS therapy, and each participant could also change CCS therapy more than once. Therefore, the number of reasons could exceed the number of participants analyzed.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=3 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Reasons Given for CCS Dose Interruption Hospitalization	33.3 percentage of reasons	—
Percentage of Reasons Given for CCS Dose Interruption Steroid Tapering	66.7 percentage of reasons	—

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants with a CCS discontinuation \>14 days were included.

Use of concomitant medications, including CCS treatment, was recorded throughout the study. Any change in CCS therapy was documented and reported among those participants who received at least one CCS before the last dose of SC TCZ. The reasons for any CCS discontinuation \>14 days were reported. More than one reason could be given for a single change in CCS therapy, and each participant could also change CCS therapy more than once. Therefore, the number of reasons could exceed the number of participants analyzed.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=2 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=27 Reasons Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Reasons Given for CCS Discontinuation AE Resolution	0 percentage of reasons	18.5 percentage of reasons
Percentage of Reasons Given for CCS Discontinuation AEs	50.0 percentage of reasons	11.1 percentage of reasons
Percentage of Reasons Given for CCS Discontinuation Prescription End	0 percentage of reasons	14.8 percentage of reasons
Percentage of Reasons Given for CCS Discontinuation RA Improvement	0 percentage of reasons	14.8 percentage of reasons
Percentage of Reasons Given for CCS Discontinuation Steroid Tapering	50.0 percentage of reasons	18.5 percentage of reasons
Percentage of Reasons Given for CCS Discontinuation Participant Request	0 percentage of reasons	7.4 percentage of reasons
Percentage of Reasons Given for CCS Discontinuation Not Specified	0 percentage of reasons	14.8 percentage of reasons

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population. The results were presented for all participants to account for multiple switches between arms (i.e., participants who started in the Q2W arm could have switched to QW and then switched back to Q2W, making them analyzable for the outcome measure).

Participants could switch between regimens at the Investigator's judgment based upon safety, efficacy, and pharmacokinetic/pharmacodynamic data. The number of participants who switched from the QW to the Q2W regimen and did not return to the QW regimen was reported.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=217 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Number of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen	14 participants	—

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population. The results were presented for all participants to account for multiple switches between arms (i.e., participants who started in the Q2W arm could have switched to QW and then switched back to Q2W, making them analyzable for the outcome measure).

Participants could switch between regimens at the Investigator's judgment based upon safety, efficacy, and pharmacokinetic/pharmacodynamic data. The percentage of participants who switched from the QW to the Q2W regimen and did not return to the QW regimen was calculated.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=217 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen	6.5 percentage of participants	—

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants who switched from the QW to Q2W regimen were included.

Participants could switch between regimens at the Investigator's judgment based upon safety, efficacy, and pharmacokinetic/pharmacodynamic data. The number of participants who switched from the QW to the Q2W regimen and thereafter returned to the QW regimen was reported with the reason for returning to the QW regimen.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=15 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Number of Participants Who Returned to the QW Regimen After Switching to the Q2W Regimen Any Reason	1 participants	—
Number of Participants Who Returned to the QW Regimen After Switching to the Q2W Regimen Investigator Recommendation	1 participants	—

SECONDARY outcome

Timeframe: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)

Population: ITT Population; only participants who switched from the QW to Q2W regimen and returned to the QW regimen were included.

Participants could switch between regimens at the Investigator's judgment based upon safety, efficacy, and pharmacokinetic/pharmacodynamic data. Time to return was defined as the time between switching to the Q2W regimen and returning to the previous QW regimen.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=1 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Time to Return to the QW Regimen After Switching to the Q2W Regimen	20 weeks	—

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

The Global Assessment of Disease Activity was performed using a 100-mm horizontal VAS. Scores may range from 0 mm ("no disease activity") to 100 mm ("maximum disease activity"), with higher scores representing an increase in perceived symptoms.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Baseline (n=44,173)	39.39 mm Standard Deviation 24.483	47.25 mm Standard Deviation 29.868
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Week 12 (n=44,172)	31.80 mm Standard Deviation 23.878	37.84 mm Standard Deviation 28.130
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Week 24 (n=43,168)	31.86 mm Standard Deviation 25.639	37.51 mm Standard Deviation 27.536
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Week 36 (n=39,159)	30.13 mm Standard Deviation 23.345	37.44 mm Standard Deviation 27.519
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Week 48 (n=18,141)	37.95 mm Standard Deviation 24.878	34.63 mm Standard Deviation 27.136
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Week 60 (n=2,92)	54.00 mm Standard Deviation 24.042	32.86 mm Standard Deviation 27.932
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Week 72 (n=1,52)	57.00 mm Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	30.83 mm Standard Deviation 28.425
Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score Week 84 (n=0,11)	NA mm Standard Deviation NA No participants provided evaluable data for the analysis	30.00 mm Standard Deviation 26.348

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The Global Assessment of Disease Activity was performed using a 100-mm horizontal VAS. Scores may range from 0 mm ("no disease activity") to 100 mm ("maximum disease activity"), with higher scores representing an increase in perceived symptoms. The change from Baseline to each visit was calculated, where positive changes represent an increase or worsening in perceived disease activity.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score Week 12 (n=44,172)	-7.59 mm Standard Deviation 22.689	-9.59 mm Standard Deviation 22.348
Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score Week 24 (n=43,168)	-6.67 mm Standard Deviation 18.977	-9.67 mm Standard Deviation 26.260
Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score Week 36 (n=39,159)	-11.59 mm Standard Deviation 23.736	-10.14 mm Standard Deviation 25.338
Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score Week 48 (n=18,141)	-5.61 mm Standard Deviation 21.892	-11.47 mm Standard Deviation 25.839
Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score Week 60 (n=2,92)	11.50 mm Standard Deviation 30.406	-9.93 mm Standard Deviation 22.992
Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score Week 72 (n=1,52)	19.00 mm Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-13.82 mm Standard Deviation 25.779
Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score Week 84 (n=0,11)	NA mm Standard Deviation NA No participants provided evaluable data for the analysis	-10.82 mm Standard Deviation 19.778

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

The Global Assessment of Pain was performed using a 100-mm horizontal VAS. Scores may range from 0 mm ("no pain") to 100 mm ("unbearable pain"), with higher scores representing an increase in pain.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Global Assessment of Pain by the Participant According to VAS Score Baseline (n=44,173)	36.89 mm Standard Deviation 23.044	45.42 mm Standard Deviation 29.448
Global Assessment of Pain by the Participant According to VAS Score Week 12 (n=44,172)	29.30 mm Standard Deviation 22.782	33.27 mm Standard Deviation 25.984
Global Assessment of Pain by the Participant According to VAS Score Week 24 (n=43,168)	29.42 mm Standard Deviation 24.509	34.48 mm Standard Deviation 24.841
Global Assessment of Pain by the Participant According to VAS Score Week 36 (n=39,159)	28.38 mm Standard Deviation 20.607	34.40 mm Standard Deviation 25.149
Global Assessment of Pain by the Participant According to VAS Score Week 60 (n=2,92)	50.00 mm Standard Deviation 14.142	30.94 mm Standard Deviation 27.635
Global Assessment of Pain by the Participant According to VAS Score Week 72 (n=1,52)	42.00 mm Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	29.20 mm Standard Deviation 26.733
Global Assessment of Pain by the Participant According to VAS Score Week 84 (n=0,11)	NA mm Standard Deviation NA No participants provided evaluable data for the analysis	25.36 mm Standard Deviation 25.598
Global Assessment of Pain by the Participant According to VAS Score Week 48 (n=18,141)	33.44 mm Standard Deviation 21.742	31.52 mm Standard Deviation 25.892

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The Global Assessment of Pain was performed using a 100-mm horizontal VAS. Scores may range from 0 mm ("no pain") to 100 mm ("unbearable pain"), with higher scores representing an increase in pain. The change from Baseline to each visit was calculated, where positive changes represent an increase or worsening in pain.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score Week 12 (n=44,172)	-7.59 mm Standard Deviation 22.145	-12.27 mm Standard Deviation 21.582
Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score Week 24 (n=43,168)	-6.63 mm Standard Deviation 20.641	-10.76 mm Standard Deviation 24.154
Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score Week 36 (n=39,159)	-10.62 mm Standard Deviation 22.783	-10.91 mm Standard Deviation 22.747
Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score Week 48 (n=18,141)	-8.00 mm Standard Deviation 18.166	-12.91 mm Standard Deviation 24.950
Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score Week 84 (n=0,11)	NA mm Standard Deviation NA No participants provided evaluable data for the analysis	-14.64 mm Standard Deviation 20.911
Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score Week 60 (n=2,92)	3.00 mm Standard Deviation 25.456	-10.07 mm Standard Deviation 22.001
Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score Week 72 (n=1,52)	3.00 mm Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-12.47 mm Standard Deviation 23.522

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

The Stanford HAQ-DI was calculated as the average of 20 questions, each scored from 0 (no difficulty) to 3 (unable to do). The questionnaire included 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common activities. Overall scores may range from 0 to 3, with higher scores representing increased disability.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Baseline (n=44,173)	0.98 units on a scale Standard Deviation 0.682	1.20 units on a scale Standard Deviation 0.729
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 12 (n=44,172)	0.95 units on a scale Standard Deviation 0.688	1.11 units on a scale Standard Deviation 0.750
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 24 (n=43,167)	0.94 units on a scale Standard Deviation 0.717	1.09 units on a scale Standard Deviation 0.725
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 36 (n=39,159)	0.95 units on a scale Standard Deviation 0.682	1.10 units on a scale Standard Deviation 0.741
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 48 (n=18,141)	0.97 units on a scale Standard Deviation 0.596	1.04 units on a scale Standard Deviation 0.745
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 60 (n=2,92)	2.13 units on a scale Standard Deviation 0.530	1.01 units on a scale Standard Deviation 0.779
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 72 (n=1,52)	2.25 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	0.97 units on a scale Standard Deviation 0.844
Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score Week 84 (n=0,11)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis.	1.14 units on a scale Standard Deviation 0.730

SECONDARY outcome

Timeframe: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

The Stanford HAQ-DI was calculated as the average of 20 questions, each scored from 0 (no difficulty) to 3 (unable to do). The questionnaire included 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common activities. Overall scores may range from 0 to 3, with higher scores representing increased disability. The change from Baseline to each visit was calculated, where positive changes represent an increased need for assistance with daily activities.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Change From Baseline in HAQ-DI Score Week 12 (n=44,172)	-0.02 units on a scale Standard Deviation 0.254	-0.10 units on a scale Standard Deviation 0.339
Change From Baseline in HAQ-DI Score Week 36 (n=39,159)	-0.08 units on a scale Standard Deviation 0.276	-0.09 units on a scale Standard Deviation 0.394
Change From Baseline in HAQ-DI Score Week 48 (n=18,141)	-0.01 units on a scale Standard Deviation 0.237	-0.14 units on a scale Standard Deviation 0.390
Change From Baseline in HAQ-DI Score Week 60 (n=2,92)	0.56 units on a scale Standard Deviation 0.795	-0.08 units on a scale Standard Deviation 0.394
Change From Baseline in HAQ-DI Score Week 72 (n=1,52)	0.88 units on a scale Standard Deviation NA Standard deviation could not be calculated because the analysis only included 1 participant.	-0.06 units on a scale Standard Deviation 0.420
Change From Baseline in HAQ-DI Score Week 84 (n=0,11)	NA units on a scale Standard Deviation NA No participants provided evaluable data for the analysis	-0.07 units on a scale Standard Deviation 0.397
Change From Baseline in HAQ-DI Score Week 24 (n=43,167)	-0.01 units on a scale Standard Deviation 0.272	-0.11 units on a scale Standard Deviation 0.372

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

The Stanford HAQ-DI was calculated as the average of 20 questions, each scored from 0 (no difficulty) to 3 (unable to do). The questionnaire included 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common activities. Overall scores may range from 0 to 3, with higher scores representing increased disability. The percentage of participants achieving a score \<0.5 was calculated at each visit.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With HAQ-DI Score <0.5 Baseline (n=44,173)	31.8 percentage of participants	17.9 percentage of participants
Percentage of Participants With HAQ-DI Score <0.5 Week 12 (n=44,172)	27.3 percentage of participants	20.9 percentage of participants
Percentage of Participants With HAQ-DI Score <0.5 Week 24 (n=43,167)	32.6 percentage of participants	23.4 percentage of participants
Percentage of Participants With HAQ-DI Score <0.5 Week 36 (n=39,159)	38.5 percentage of participants	24.5 percentage of participants
Percentage of Participants With HAQ-DI Score <0.5 Week 48 (n=18,141)	27.8 percentage of participants	24.8 percentage of participants
Percentage of Participants With HAQ-DI Score <0.5 Week 60 (n=2,92)	0.0 percentage of participants	29.3 percentage of participants
Percentage of Participants With HAQ-DI Score <0.5 Week 72 (n=1,52)	0.0 percentage of participants	34.6 percentage of participants
Percentage of Participants With HAQ-DI Score <0.5 Week 84 (n=0,11)	NA percentage of participants No participants provided evaluable data for the analysis	9.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

Low disease activity was defined as DAS28 ≤3.2, SDAI ≤11, or CDAI ≤10. For each formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The DAS28 was calculated as (0.56 × square root of TJC) + (0.28 × square root of SJC) + (0.7 × ln ESR) + (0.014 × VAS), with potential scores from 0 to 10. The SDAI was calculated as SJC + TJC + VAS (participant) + VAS (physician) + hsCRP, with potential scores from 0 to infinity. However, based upon normal hsCRP level within 1 mg/dL, scores would be expected to fall within ≤77 points. The CDAI was calculated as SJC + TJC + VAS (participant) + VAS (physician), with potential scores from 0 to 76. For all instruments, higher scores indicate increased disease activity. The number of participants who met criteria for low disease activity was reported at each visit.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Baseline, DAS28 (n=44,172)	11 participants	46 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Baseline, SDAI (n=44,170)	14 participants	43 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Baseline, CDAI (n=44,173)	13 participants	41 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 12, DAS28 (n=44,172)	21 participants	81 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 12, SDAI (n=44,172)	22 participants	65 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 12, CDAI (n=44,172)	20 participants	63 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 24, DAS28 (n=43,168)	23 participants	82 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 24, SDAI (n=41,166)	19 participants	67 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 24, CDAI (n=42,166)	20 participants	60 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 36, DAS28 (n=39,159)	21 participants	75 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 36, CDAI (n=39,159)	21 participants	60 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 48, DAS28 (n=18,141)	10 participants	69 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 48, SDAI (n=18,140)	8 participants	63 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 48, CDAI (n=18,140)	7 participants	59 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 60, DAS28 (n=2,92)	0 participants	52 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 60, SDAI (n=2,92)	0 participants	40 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 60, CDAI (n=2,92)	0 participants	37 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 72, DAS28 (n=1,52)	0 participants	28 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 72, SDAI (n=1,52)	0 participants	26 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 72, CDAI (n=1,52)	0 participants	25 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 84, DAS28 (n=0,11)	NA participants No participants provided evaluable data for the analysis	6 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 84, SDAI (n=0,11)	NA participants No participants provided evaluable data for the analysis	4 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 84, CDAI (n=0,11)	NA participants No participants provided evaluable data for the analysis	4 participants
Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 36, SDAI (n=39,159)	20 participants	61 participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population; only those participants who provided evaluable data (n) were included in the analysis.

Low disease activity was defined as DAS28 ≤3.2, SDAI ≤11, or CDAI ≤10. For each formula, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The DAS28 was calculated as (0.56 × square root of TJC) + (0.28 × square root of SJC) + (0.7 × ln ESR) + (0.014 × VAS), with potential scores from 0 to 10. The SDAI was calculated as SJC + TJC + VAS (participant) + VAS (physician) + hsCRP, with potential scores from 0 to infinity. However, based upon normal hsCRP level within 1 mg/dL, scores would be expected to fall within ≤77 points. The CDAI was calculated as SJC + TJC + VAS (participant) + VAS (physician), with potential scores from 0 to 76. For all instruments, higher scores indicate increased disease activity. The percentage of participants who met criteria for low disease activity was calculated at each visit.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 12, CDAI (n=44,172)	45.5 percentage of participants	36.6 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 24, DAS28 (n=43,168)	53.5 percentage of participants	48.8 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 24, SDAI (n=41,166)	46.3 percentage of participants	40.4 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 24, CDAI (n=42,166)	47.6 percentage of participants	36.1 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 36, SDAI (n=39,159)	51.3 percentage of participants	38.4 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 48, SDAI (n=18,140)	44.4 percentage of participants	45.0 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 48, CDAI (n=18,140)	38.9 percentage of participants	42.1 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 60, DAS28 (n=2,92)	0.0 percentage of participants	56.5 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 60, SDAI (n=2,92)	0.0 percentage of participants	43.5 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 72, DAS28 (n=1,52)	0.0 percentage of participants	53.8 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 72, CDAI (n=1,52)	0.0 percentage of participants	48.1 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 84, DAS28 (n=0,11)	NA percentage of participants No participants provided evaluable data for the analysis	54.5 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Baseline, DAS28 (n=44,172)	25.0 percentage of participants	26.7 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Baseline, SDAI (n=44,170)	31.8 percentage of participants	25.3 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Baseline, CDAI (n=44,173)	29.5 percentage of participants	23.7 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 12, DAS28 (n=44,172)	47.7 percentage of participants	47.1 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 12, SDAI (n=44,172)	50.0 percentage of participants	37.8 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 36, DAS28 (n=39,159)	53.8 percentage of participants	47.2 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 36, CDAI (n=39,159)	53.8 percentage of participants	37.7 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 48, DAS28 (n=18,141)	55.6 percentage of participants	48.9 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 60, CDAI (n=2,92)	0.0 percentage of participants	40.2 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 72, SDAI (n=1,52)	0.0 percentage of participants	50.0 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 84, SDAI (n=0,11)	NA percentage of participants No participants provided evaluable data for the analysis	36.4 percentage of participants
Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria Week 84, CDAI (n=0,11)	NA percentage of participants No participants provided evaluable data for the analysis	36.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

Remission was defined as DAS28 \<2.6, SDAI ≤3.3, or meeting all Boolean criteria (28-count SJC and TJC ≤1, VAS ≤10 mm, and hsCRP ≤1 mg/dL). For DAS28 and SDAI formulas, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The DAS28 was calculated as (0.56 × square root of TJC) + (0.28 × square root of SJC) + (0.7 × ln ESR) + (0.014 × VAS), with potential scores from 0 to 10. The SDAI was calculated as SJC + TJC + VAS (participant) + VAS (physician) + hsCRP, with potential scores from 0 to infinity. However, based upon normal hsCRP level within 1 mg/dL, scores would be expected to fall within ≤77 points. For these instruments, higher scores indicate increased disease activity. The number of participants who met criteria for remission was reported at each visit.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 36, SDAI (n=39,159)	7 participants	21 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 36, Boolean (n=39,161)	3 participants	17 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 72, DAS28 (n=1,52)	0 participants	22 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 72, Boolean (n=1,54)	0 participants	10 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 84, DAS28 (n=0,11)	NA participants No participants provided evaluable data for the analysis	6 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 84, Boolean (n=0,11)	NA participants No participants provided evaluable data for the analysis	2 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Baseline, DAS28 (n=44,172)	6 participants	33 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Baseline, SDAI (n=44,170)	2 participants	15 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Baseline, Boolean (n=44,172)	1 participants	14 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 12, DAS28 (n=44,172)	14 participants	61 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 12, SDAI (n=44,172)	7 participants	20 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 12, Boolean (n=44,172)	4 participants	15 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 24, DAS28 (n=43,168)	18 participants	61 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 24, SDAI (n=41,166)	8 participants	23 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 24, Boolean (n=43,170)	5 participants	16 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 36, DAS28 (n=39,159)	15 participants	57 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 48, DAS28 (n=18,141)	9 participants	51 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 48, SDAI (n=18,140)	1 participants	15 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 48, Boolean (n=18,143)	1 participants	14 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 60, DAS28 (n=2,92)	0 participants	39 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 60, SDAI (n=2,92)	0 participants	17 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 60, Boolean (n=2,93)	0 participants	14 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 72, SDAI (n=1,52)	0 participants	11 participants
Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 84, SDAI (n=0,11)	NA participants No participants provided evaluable data for the analysis	2 participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84

Population: ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided data for the outcome measure. The number of participants who provided data for each analysis (n) is shown in the table.

Remission was defined as DAS28 \<2.6, SDAI ≤3.3, or meeting all Boolean criteria (28-count SJC and TJC ≤1, VAS ≤10 mm, and hsCRP ≤1 mg/dL). For DAS28 and SDAI formulas, the SJC and TJC values were based upon 28 joints, and VAS was transformed from a 100-mm scale to a 10-point score. The DAS28 was calculated as (0.56 × square root of TJC) + (0.28 × square root of SJC) + (0.7 × ln ESR) + (0.014 × VAS), with potential scores from 0 to 10. The SDAI was calculated as SJC + TJC + VAS (participant) + VAS (physician) + hsCRP, with potential scores from 0 to infinity. However, based upon normal hsCRP level within 1 mg/dL, scores would be expected to fall within ≤77 points. For these instruments, higher scores indicate increased disease activity. The percentage of participants who met criteria for remission was calculated at each visit.

Outcome measures

Outcome measures
Measure	SC TCZ Q2W n=44 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 Participants Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 12, DAS28 (n=44,172)	31.8 percentage of participants	35.5 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 12, SDAI (n=44,172)	15.9 percentage of participants	11.6 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 24, SDAI (n=41,166)	19.5 percentage of participants	13.9 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 36, Boolean (n=39,161)	7.7 percentage of participants	10.6 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 48, DAS28 (n=18,141)	50.0 percentage of participants	36.2 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 60, Boolean (n=2,93)	0.0 percentage of participants	15.1 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 72, DAS28 (n=1,52)	0.0 percentage of participants	42.3 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 72, Boolean (n=1,54)	0.0 percentage of participants	18.5 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Baseline, DAS28 (n=44,172)	13.6 percentage of participants	19.2 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Baseline, SDAI (n=44,170)	4.5 percentage of participants	8.8 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Baseline, Boolean (n=44,172)	2.3 percentage of participants	8.1 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 12, Boolean (n=44,172)	9.1 percentage of participants	8.7 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 24, DAS28 (n=43,168)	41.9 percentage of participants	36.3 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 24, Boolean (n=43,170)	11.6 percentage of participants	9.4 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 36, DAS28 (n=39,159)	38.5 percentage of participants	35.8 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 36, SDAI (n=39,159)	17.9 percentage of participants	13.2 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 48, SDAI (n=18,140)	5.6 percentage of participants	10.7 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 48, Boolean (n=18,143)	5.6 percentage of participants	9.8 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 60, DAS28 (n=2,92)	0.0 percentage of participants	42.4 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 60, SDAI (n=2,92)	0.0 percentage of participants	18.5 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 72, SDAI (n=1,52)	0.0 percentage of participants	21.2 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 84, DAS28 (n=0,11)	NA percentage of participants No participants provided evaluable data for the analysis	54.5 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 84, SDAI (n=0,11)	NA percentage of participants No participants provided evaluable data for the analysis	18.2 percentage of participants
Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria Week 84, Boolean (n=0,11)	NA percentage of participants No participants provided evaluable data for the analysis	18.2 percentage of participants

Adverse Events

SC TCZ Q2W

Serious events: 4 serious events

Other events: 22 other events

Deaths: 0 deaths

SC TCZ QW

Serious events: 19 serious events

Other events: 102 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	SC TCZ Q2W n=44 participants at risk Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 participants at risk Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Infections and infestations Upper respiratory tract infection	18.2% 8/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	20.2% 35/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Sinusitis	4.5% 2/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	12.7% 22/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Nasopharyngitis	4.5% 2/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	11.6% 20/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Urinary tract infection	4.5% 2/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	8.7% 15/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Bronchitis	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	6.4% 11/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Musculoskeletal and connective tissue disorders Arthralgia	4.5% 2/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	6.9% 12/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Musculoskeletal and connective tissue disorders Back pain	4.5% 2/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	5.2% 9/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Injury, poisoning and procedural complications Fall	6.8% 3/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	3.5% 6/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Injury, poisoning and procedural complications Contusion	6.8% 3/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	2.9% 5/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Investigations Alanine aminotransferase increased	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	6.9% 12/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Gastrointestinal disorders Diarrhoea	6.8% 3/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	4.6% 8/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Skin and subcutaneous tissue disorders Rash	6.8% 3/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	3.5% 6/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Vascular disorders Hypertension	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	5.2% 9/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

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	SC TCZ Q2W n=44 participants at risk Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received SC TCZ continued at their same dosage of SC TCZ 162 mg Q2W.	SC TCZ QW n=173 participants at risk Participants with moderate to severe RA who completed treatment with SC or IV TCZ in one of the core studies WA22762 (NCT01194414) or NA25220 (NCT01232569) received treatment in this LTE study for an additional 96 weeks. Participants who received IV TCZ in the previous trial were switched to SC TCZ 162 mg QW, and those who received SC TCZ continued at their same dosage of SC TCZ 162 mg QW.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
General disorders Chest pain	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
General disorders Device malfunction	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Cellulitis	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	1.2% 2/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	1.2% 2/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Arthritis bacterial	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Bronchopneumonia	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Endocarditis	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Endophthalmitis	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.00% 0/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Infections and infestations Pyelonephritis	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.00% 0/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Nervous system disorders Syncope	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Nervous system disorders Transient ischaemic attack	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	1.2% 2/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Nervous system disorders Cerebrovascular accident	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Gastrointestinal disorders Abdominal compartment syndrome	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.00% 0/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Gastrointestinal disorders Diverticular perforation	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Gastrointestinal disorders Pancreatitis	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Vascular disorders Deep vein thrombosis	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.00% 0/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Vascular disorders Hypertension	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial stromal sarcoma	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.00% 0/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Psychiatric disorders Mental status change	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Renal and urinary disorders Haematuria	2.3% 1/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.00% 0/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/44 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.	0.58% 1/173 • From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall) Safety Population.