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

Percentage of Participants Who Correctly Administered All SC TCZ Doses

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.

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

Disease Activity Score Based on 28 Joints (DAS28) Score

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.

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

Change From Baseline in DAS28 Score

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.

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

Clinical Disease Activity Index (CDAI) Score

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.

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

Change From Baseline in CDAI Score

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.

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

Simplified Disease Activity Index (SDAI) Score

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.

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

Change From Baseline in SDAI Score

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.

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

Tender Joint Count (TJC) Score

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.

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

Change From Baseline in TJC Score

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.

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

Swollen Joint Count (SJC) Score

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.

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

Change From Baseline in SJC Score

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.

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

Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation

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.

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

Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation

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.

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

Percentage of Reasons Given for DMARD Dose Reduction or Interruption

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.

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

Percentage of Reasons Given for DMARD Discontinuation

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.

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

Number of Participants With a Corticosteroid (CCS) Dose Reduction, Interruption, or Discontinuation

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.

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

Percentage of Participants With a CCS Dose Reduction, Interruption, or Discontinuation

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.

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

Percentage of Reasons Given for CCS Dose Reduction

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.

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

Percentage of Reasons Given for 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.

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

Percentage of Reasons Given for CCS Discontinuation

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.

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

Number of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen

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.

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

Percentage of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen

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.

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

Number of Participants Who Returned to the QW Regimen After Switching to the Q2W Regimen

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.

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

Time to Return to the QW Regimen After Switching to the Q2W Regimen

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.

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

Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score

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.

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

Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score

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.

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

Global Assessment of Pain by the Participant According to VAS Score

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.

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

Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score

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.

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

Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score

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.

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

Change From Baseline in HAQ-DI Score

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.

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

Percentage of Participants With HAQ-DI Score <0.5

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.

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

Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria

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.

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

Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria

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.

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

Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria

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.

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

Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria

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.

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