Clincosm LogoSign in Get a demo

ACT-MOVE: A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02046603
Collaborator
(none)
162
Enrollment
38
Locations
2
Arms
29
Actual Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label study will evaluate the efficacy and safety of tocilizumab as monotherapy or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) in participants with active rheumatoid arthritis (RA) and an inadequate response to current non-biologic DMARD therapy or the first anti-tumour necrosis factor (anti-TNF) agent. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously once a week for 52 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
162 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-Label, Phase IIIb Study to Evaluate the Efficacy and Safety of Subcutaneous (SC) Tocilizumab Monotherapy or Combination Therapy With Methotrexate (MTX) or Other Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Patients With Active Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-Tumour Necrosis Factor (Anti-TNF) Biologic Agent
Actual Study Start Date :
Mar 4, 2014
Actual Primary Completion Date :
Aug 4, 2016
Actual Study Completion Date :
Aug 4, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tocilizumab Monotherapy

Participants will receive a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.

Drug: Tocilizumab
Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.
Other Names:
  • RoActemra, Actemra

    		•
    Experimental: Tocilizumab in Combination With Methotrexate or Other DMARDs

    Participants will receive a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.

    Drug: Tocilizumab
    Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.
    Other Names:
  • RoActemra, Actemra

    • Drug: DMARDs
    Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study. The study protocol does not specify any particular therapy.

    Drug: Oral Corticosteroids
    Stable oral corticosteroids doses (≤10 mg/day prednisone or equivalent) are allowed. The study protocol does not specify any additional detail on types of oral corticosteroids.

    Drug: Methotrexate
    Methotrexate per investigator's discretion.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2 [Baseline, Week 2]

      DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour [mm/hour]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale [VAS] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR greater than or equal to (≥) 2.6 to less than or equal to (≤) 3.2 implied low disease activity, greater than (>) 3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and less than (<) 2.6 implied clinical remission.

    2. Change From Baseline in DAS28-ESR at Week 4 [Baseline, Week 4]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    3. Change From Baseline in DAS28-ESR at Week 8 [Baseline, Week 8]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    4. Change From Baseline in DAS28-ESR at Week 12 [Baseline, Week 12]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    5. Change From Baseline in DAS28-ESR at Week 16 [Baseline, Week 16]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    6. Change From Baseline in DAS28-ESR at Week 20 [Baseline, Week 20]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    7. Change From Baseline in DAS28-ESR at Week 24 [Baseline, Week 24]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    8. Change From Baseline in DAS28-ESR at Week 28 [Baseline, Week 28]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    9. Change From Baseline in DAS28-ESR at Week 32 [Baseline, Week 32]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    10. Change From Baseline in DAS28-ESR at Week 36 [Baseline, Week 36]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    11. Change From Baseline in DAS28-ESR at Week 40 [Baseline, Week 40]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    12. Change From Baseline in DAS28-ESR at Week 44 [Baseline, Week 44]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    13. Change From Baseline in DAS28-ESR at Week 48 [Baseline, Week 48]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    14. Change From Baseline in DAS28-ESR at Week 52 [Baseline, Week 52]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    15. Change From Baseline in DAS28-ESR at Early Withdrawal [Baseline, early withdrawal (up to Week 52)]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.

    Secondary Outcome Measures

    1. Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or ESR).

    2. Number of Participants Achieving an ACR50 Response [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).

    3. Number of Participants Achieving an ACR70 Response [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).

    4. Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline >1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline >0.6 to ≤1.2 with a DAS28 score >5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.

    5. Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI ≤3.3 indicates clinical remission, >3.3 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.

    6. Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI ≤2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity.

    7. Percent Change From Baseline in Total TJC on 68 Joints at Week 52 [Baseline, Week 52]

      Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 68. A reduction in number of tender joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).

    8. Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of tender joints compared to baseline indicates improvement.

    9. Percent Change From Baseline in Total SJC on 66 Joints at Week 52 [Baseline, Week 52]

      Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 66. A reduction in number of swollen joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).

    10. Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of swollen joints compared to baseline indicates improvement.

    11. Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2 [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity.

    12. Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6 [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR <2.6 implied clinical remission.

    13. Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, at early withdrawal (up to Week 52), follow-up Week 4 (up to Week 56), and follow-up Week 8 (up to Week 60)]

      Results are reported for number of participants who had non-biologic DMARD/corticosteroid dose reductions and/or discontinuation by reasons for dose reductions or discontinuation (safety reasons, discomfort, lack of efficacy, other reasons, and unknown reasons). Participants may be included under more than one reason.

    14. Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire [Baseline, Weeks 12, 24, 36, 52, and at early withdrawal (up to Week 52)]

      Methotrexate adherence was determined from responses to the question 'Over the last 3 months you were prescribed 12 doses of methotrexate, how many (approximately) have you taken?' Adherence (%) was calculated as: (Approximate number of doses taken/12)*100.

    15. Patient Global Assessment of Disease Activity VAS Score [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.

    16. Patient Pain VAS Score [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.

    17. Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.

    18. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score).

    19. Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records [Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)]

      A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.

    20. Number of Participants With Anti-Tocilizumab Antibodies [Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)]

    21. Serum Levels of Tocilizumab [Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)]

    22. Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs) [Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria

    • Participants who have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF agent (in monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as DAS28 score improvement of less than 1.2 or participants achieving a DAS28 score improvement of 1.2 but not achieving low disease activity (current DAS28-ESR above 3.2) according to a treat-to-target strategy and have not been previously exposed to treatment with tocilizumab. Inadequate response to non-biologic DMARD therapy will be assessed according to local guidelines and the participants will need to be eligible for biologic therapy according to local guidelines

    • Oral corticosteroids (≤10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to recommended dose) are permitted if on stable dose regimen for greater than or equal to [≥] 4 weeks prior to baseline

    • Permitted non-biologic DMARDs are allowed if on stable dose for at least 4 weeks prior to baseline

    • Receiving treatment on an outpatient basis, not including tocilizumab

    • Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of tocilizumab

    Exclusion Criteria:

    • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline

    • Rheumatic autoimmune disease other than RA

    • Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis

    • Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16

    • Prior history of or current inflammatory joint disease other than RA

    • Exposure to tocilizumab either intravenous or SC at any time prior to baseline

    • Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening

    • Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline

    • History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies

    • Known active current or history of recurrent infections

    • Major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening

    • Active tuberculosis (TB) requiring treatment within the previous 3 years

    • Positive for hepatitis B or hepatitis C virus infection

    • Primary or secondary immunodeficiency (history of or currently active)

    • Pregnant or lactating women

    • Inadequate hematologic, renal or liver function

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aberdeen Royal Infirmary Aberdeen United Kingdom AB25 2ZN
    2 Christchurch Hospital; Rheumatology Bournemouth United Kingdom BH23 2JX
    3 Royal Sussex County Hospital; Clinical Investigation Research Unit Brighton United Kingdom BN2 5BE
    4 Queens Hospital Burton on Trent United Kingdom DE13 0RB
    5 West Suffolk Hospital Bury Saint Edmonds United Kingdom IP33 2QZ
    6 Addenbrooke'S Hospital; Rheumatology Research Unit Cambridge United Kingdom CB2 2QQ
    7 Cannock Chase Hospital; Rheumatology Cannock United Kingdom WS11 5XY
    8 University Hospital of Wales; Dept of Rhematology Cardiff United Kingdom CF14 4XW
    9 Broomfield Hospital Chelmsford United Kingdom CM1 7ET
    10 Countess of Chester Hospital; Dept of Rheumatology Chester United Kingdom CH2 1UL
    11 Dewsbury & District Hospital; Dept of Rheumatology Dewsbury United Kingdom WF13 4HS
    12 Russells Hall Hospital; Rheumatology Department Dudley United Kingdom DY1 2HQ
    13 Ninewells Hospital Dundee United Kingdom DD12 9SY
    14 Eastbourne District General Hospital; Dept of Rheumatology Eastbourne United Kingdom BN21 2UD
    15 Western General Hospital; Pharmacy Department Edinburgh United Kingdom EH4 2XU
    16 Gartnavel General Hospital; Rheumatology Glasgow United Kingdom G12 0YN
    17 Diana Princess of Wales Hosp. Grimsby United Kingdom DN33 2BA
    18 Princess Alexandra Hospital Harlow United Kingdom CM20 1QX
    19 Northwick Park Hospital Harrow United Kingdom HA1 3UJ
    20 Hemel Hempstead General Hospital; Rheumatology Dept Hemel Hempstead United Kingdom HP2 4AD
    21 Hull Royal Infirmary; Rheumatology Department Hull United Kingdom HU3 3JZ
    22 Llandudno General Hospital Llandudno United Kingdom LL30 1LB
    23 Whipps Cross Hospital; Rheumatology Dept London United Kingdom E11 1NR
    24 Royal Free Hospital; Department of Rheumatology London United Kingdom NW3 2QG
    25 Maidstone Hospital; Dept of Rheumatology Maidstone United Kingdom ME16 9QQ
    26 Wythenshawe Hospital Manchester United Kingdom M23 9QZ
    27 Freeman Hospital; Dept of Rheumatology Newcastle Upon Tyne United Kingdom NE7 7DN
    28 North Tyneside General Hospital North Shields United Kingdom NE29 8NH
    29 Norfolk & Norwich Hospital; Rheumatology Norwich United Kingdom NR4 7UY
    30 Integrated Care Centre Oldham United Kingdom OL1 1NL
    31 Solihull Hospital Solihull United Kingdom B91 2JL
    32 Haywood Hospital; Staffordshire Rheumatology Centre Stoke-on-trent United Kingdom ST6 7AG
    33 Great Western Hospital; Dept of Rheumatology Swindon United Kingdom SN3 6BB
    34 Torbay Hospital; Dept of Rhematology Torquay United Kingdom TQ2 7AA
    35 Royal Cornwall Hospital; Rhuematololgy Dept Truro United Kingdom TR1 3LJ
    36 Warrington Hospital Warrington United Kingdom WA5 1QG
    37 Wrightington Hospital; Rheumatology Wigan United Kingdom WN6 9EW
    38 Wishaw General Hospital Wishaw United Kingdom ML2 0DP

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02046603
    Other Study ID Numbers:
    • ML28641
    • 2013-000054-22
    First Posted:
    Jan 28, 2014
    Last Update Posted:
    Dec 7, 2018
    Last Verified:
    May 1, 2018
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Methotrexate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 162 participants were enrolled. One participant who did not receive a dose of tocilizumab was excluded from the full analysis set (FAS) and the results are reported for 161 participants.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly subcutaneous (SC) injection of tocilizumab 162 milligrams (mg) as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) for 52 weeks.
    Period Title: Overall Study
    STARTED 22 140
    Received at Least 1 Dose of Tocilizumab 21 140
    COMPLETED 7 65
    NOT COMPLETED 15 75

    Baseline Characteristics

    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs Total
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks. Total of all reporting groups
    Overall Participants 21 140 161
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53.9
    (13.63)
    55.3
    (10.76)
    55.1
    (11.14)
    Sex: Female, Male (Count of Participants)
    Female
    16
    76.2%
    104
    74.3%
    120
    74.5%
    Male
    5
    23.8%
    36
    25.7%
    41
    25.5%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2
    Description DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour [mm/hour]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale [VAS] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR greater than or equal to (≥) 2.6 to less than or equal to (≤) 3.2 implied low disease activity, greater than (>) 3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and less than (<) 2.6 implied clinical remission.
    Time Frame Baseline, Week 2

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 139
    Baseline
    5.52
    (1.014)
    5.53
    (1.257)
    Change at Week 2
    -1.41
    (0.994)
    -1.22
    (1.131)
    2. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 4
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 4

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 137
    Mean (Standard Deviation) [units on a scale]
    -1.86
    (1.016)
    -2.11
    (1.215)
    3. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 8
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 8

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 18 131
    Mean (Standard Deviation) [units on a scale]
    -2.42
    (1.352)
    -2.62
    (1.482)
    4. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 12
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 12

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 19 128
    Mean (Standard Deviation) [units on a scale]
    -2.33
    (1.522)
    -2.99
    (1.510)
    5. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 16
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 16

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 18 125
    Mean (Standard Deviation) [units on a scale]
    -2.93
    (1.218)
    -3.07
    (1.532)
    6. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 20
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 20

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 19 121
    Mean (Standard Deviation) [units on a scale]
    -3.17
    (1.346)
    -3.13
    (1.525)
    7. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 24
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 19 117
    Mean (Standard Deviation) [units on a scale]
    -3.28
    (1.379)
    -3.33
    (1.470)
    8. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 28
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 28

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 19 115
    Mean (Standard Deviation) [units on a scale]
    -3.54
    (1.260)
    -3.32
    (1.552)
    9. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 32
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 32

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 19 115
    Mean (Standard Deviation) [units on a scale]
    -3.19
    (1.418)
    -3.54
    (1.448)
    10. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 36
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 36

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 18 114
    Mean (Standard Deviation) [units on a scale]
    -3.57
    (1.358)
    -3.55
    (1.589)
    11. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 40
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 40

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 17 111
    Mean (Standard Deviation) [units on a scale]
    -3.82
    (1.143)
    -3.64
    (1.524)
    12. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 44
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 44

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 17 107
    Mean (Standard Deviation) [units on a scale]
    -3.61
    (1.325)
    -3.65
    (1.574)
    13. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 48
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 16 107
    Mean (Standard Deviation) [units on a scale]
    -3.54
    (1.146)
    -3.65
    (1.552)
    14. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Week 52
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 15 107
    Mean (Standard Deviation) [units on a scale]
    -3.75
    (1.361)
    -3.67
    (1.592)
    15. Primary Outcome
    Title Change From Baseline in DAS28-ESR at Early Withdrawal
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
    Time Frame Baseline, early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 5 28
    Mean (Standard Deviation) [units on a scale]
    -2.88
    (1.236)
    -1.63
    (1.480)
    16. Secondary Outcome
    Title Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response
    Description A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or ESR).
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Week 2
    6
    28.6%
    23
    16.4%
    Week 4
    6
    28.6%
    68
    48.6%
    Week 8
    11
    52.4%
    69
    49.3%
    Week 12
    10
    47.6%
    83
    59.3%
    Week 16
    13
    61.9%
    83
    59.3%
    Week 20
    15
    71.4%
    86
    61.4%
    Week 24
    15
    71.4%
    90
    64.3%
    Week 28
    14
    66.7%
    87
    62.1%
    Week 32
    13
    61.9%
    89
    63.6%
    Week 36
    12
    57.1%
    92
    65.7%
    Week 40
    13
    61.9%
    91
    65%
    Week 44
    12
    57.1%
    88
    62.9%
    Week 48
    12
    57.1%
    87
    62.1%
    Week 52
    12
    57.1%
    88
    62.9%
    Early withdrawal
    3
    14.3%
    10
    7.1%
    17. Secondary Outcome
    Title Number of Participants Achieving an ACR50 Response
    Description A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Week 2
    0
    0%
    5
    3.6%
    Week 4
    3
    14.3%
    20
    14.3%
    Week 8
    6
    28.6%
    43
    30.7%
    Week 12
    8
    38.1%
    54
    38.6%
    Week 16
    7
    33.3%
    62
    44.3%
    Week 20
    9
    42.9%
    61
    43.6%
    Week 24
    9
    42.9%
    64
    45.7%
    Week 28
    13
    61.9%
    68
    48.6%
    Week 32
    8
    38.1%
    69
    49.3%
    Week 36
    9
    42.9%
    74
    52.9%
    Week 40
    9
    42.9%
    71
    50.7%
    Week 44
    10
    47.6%
    72
    51.4%
    Week 48
    11
    52.4%
    73
    52.1%
    Week 52
    8
    38.1%
    73
    52.1%
    Early withdrawal
    2
    9.5%
    4
    2.9%
    18. Secondary Outcome
    Title Number of Participants Achieving an ACR70 Response
    Description A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Week 2
    0
    0%
    0
    0%
    Week 4
    1
    4.8%
    9
    6.4%
    Week 8
    4
    19%
    19
    13.6%
    Week 12
    3
    14.3%
    30
    21.4%
    Week 16
    3
    14.3%
    32
    22.9%
    Week 20
    7
    33.3%
    37
    26.4%
    Week 24
    5
    23.8%
    38
    27.1%
    Week 28
    6
    28.6%
    44
    31.4%
    Week 32
    6
    28.6%
    47
    33.6%
    Week 36
    7
    33.3%
    48
    34.3%
    Week 40
    8
    38.1%
    49
    35%
    Week 44
    6
    28.6%
    53
    37.9%
    Week 48
    8
    38.1%
    56
    40%
    Week 52
    7
    33.3%
    54
    38.6%
    Early withdrawal
    2
    9.5%
    1
    0.7%
    19. Secondary Outcome
    Title Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR
    Description DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline >1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline >0.6 to ≤1.2 with a DAS28 score >5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Week 2: No response
    4
    19%
    56
    40%
    Week 2: Moderate response
    10
    47.6%
    56
    40%
    Week 2: Good response
    7
    33.3%
    25
    17.9%
    Week 4: No response
    3
    14.3%
    22
    15.7%
    Week 4: Moderate response
    7
    33.3%
    58
    41.4%
    Week 4: Good response
    11
    52.4%
    57
    40.7%
    Week 8: No response
    1
    4.8%
    11
    7.9%
    Week 8: Moderate response
    9
    42.9%
    48
    34.3%
    Week 8: Good response
    8
    38.1%
    72
    51.4%
    Week 12: No response
    4
    19%
    11
    7.9%
    Week 12: Moderate response
    3
    14.3%
    34
    24.3%
    Week 12: Good response
    12
    57.1%
    83
    59.3%
    Week 16: No response
    1
    4.8%
    9
    6.4%
    Week 16: Moderate response
    4
    19%
    30
    21.4%
    Week 16: Good response
    13
    61.9%
    86
    61.4%
    Week 20: No response
    0
    0%
    9
    6.4%
    Week 20: Moderate response
    5
    23.8%
    27
    19.3%
    Week 20: Good response
    14
    66.7%
    85
    60.7%
    Week 24: No response
    1
    4.8%
    7
    5%
    Week 24: Moderate response
    2
    9.5%
    21
    15%
    Week 24: Good response
    16
    76.2%
    89
    63.6%
    Week 28: No response
    1
    4.8%
    5
    3.6%
    Week 28: Moderate response
    0
    0%
    24
    17.1%
    Week 28: Good response
    18
    85.7%
    86
    61.4%
    Week 32: No response
    1
    4.8%
    3
    2.1%
    Week 32: Moderate response
    2
    9.5%
    21
    15%
    Week 32: Good response
    16
    76.2%
    91
    65%
    Week 36: No response
    0
    0%
    4
    2.9%
    Week 36: Moderate response
    3
    14.3%
    19
    13.6%
    Week 36: Good response
    15
    71.4%
    91
    65%
    Week 40: No response
    0
    0%
    2
    1.4%
    Week 40: Moderate response
    1
    4.8%
    15
    10.7%
    Week 40: Good response
    16
    76.2%
    94
    67.1%
    Week 44: No response
    0
    0%
    5
    3.6%
    Week 44: Moderate response
    2
    9.5%
    15
    10.7%
    Week 44: Good response
    15
    71.4%
    87
    62.1%
    Week 48: No response
    0
    0%
    4
    2.9%
    Week 48: Moderate response
    2
    9.5%
    13
    9.3%
    Week 48: Good response
    14
    66.7%
    90
    64.3%
    Week 52: No response
    0
    0%
    5
    3.6%
    Week 52: Moderate response
    3
    14.3%
    12
    8.6%
    Week 52: Good response
    12
    57.1%
    90
    64.3%
    Early Withdrawal: No response
    0
    0%
    11
    7.9%
    Early Withdrawal: Moderate response
    1
    4.8%
    8
    5.7%
    Early Withdrawal: Good response
    4
    19%
    9
    6.4%
    20. Secondary Outcome
    Title Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
    Description The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI ≤3.3 indicates clinical remission, >3.3 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 136
    Baseline
    31.23
    (11.892)
    32.33
    (11.620)
    Change at Week 2
    -9.80
    (10.406)
    -6.94
    (9.710)
    Change at Week 4
    -12.64
    (10.502)
    -13.92
    (10.666)
    Change at Week 8
    -19.75
    (12.978)
    -17.21
    (12.900)
    Change at Week 12
    -14.65
    (15.003)
    -20.26
    (12.739)
    Change at Week 16
    -19.48
    (9.649)
    -21.16
    (11.945)
    Change at Week 20
    -23.67
    (14.015)
    -20.50
    (11.630)
    Change at Week 24
    -24.31
    (13.469)
    -23.48
    (12.417)
    Change at Week 28
    -24.87
    (12.554)
    -23.26
    (12.418)
    Change at Week 32
    -22.98
    (12.850)
    -24.94
    (11.399)
    Change at Week 36
    -26.32
    (12.795)
    -24.65
    (11.268)
    Change at Week 40
    -27.29
    (13.280)
    -25.46
    (12.210)
    Change at Week 44
    -27.71
    (12.851)
    -26.08
    (11.835)
    Change at Week 48
    -26.83
    (13.615)
    -26.13
    (11.189)
    Change at Week 52
    -27.45
    (14.351)
    -26.15
    (12.791)
    Change at early withdrawal
    -18.94
    (14.681)
    -9.45
    (12.533)
    21. Secondary Outcome
    Title Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
    Description The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI ≤2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 139
    Baseline
    29.69
    (11.209)
    30.88
    (10.953)
    Change at Week 2
    -8.35
    (10.433)
    -5.16
    (9.323)
    Change at Week 4
    -11.87
    (10.062)
    -12.26
    (10.137)
    Change at Week 8
    -17.74
    (12.289)
    -15.63
    (11.873)
    Change at Week 12
    -15.39
    (14.216)
    -18.66
    (11.895)
    Change at Week 16
    -20.70
    (11.694)
    -19.51
    (11.124)
    Change at Week 20
    -22.19
    (13.545)
    -19.23
    (11.433)
    Change at Week 24
    -22.88
    (12.720)
    -21.96
    (11.825)
    Change at Week 28
    -23.43
    (11.573)
    -21.48
    (11.585)
    Change at Week 32
    -21.55
    (12.019)
    -23.20
    (10.842)
    Change at Week 36
    -24.86
    (11.854)
    -23.10
    (11.263)
    Change at Week 40
    -25.74
    (12.488)
    -24.01
    (11.282)
    Change at Week 44
    -25.42
    (11.971)
    -24.42
    (11.186)
    Change at Week 48
    -25.36
    (12.718)
    -24.59
    (10.645)
    Change at Week 52
    -25.48
    (13.049)
    -24.42
    (12.599)
    Change at early withdrawal
    -17.78
    (14.667)
    -8.68
    (11.909)
    22. Secondary Outcome
    Title Percent Change From Baseline in Total TJC on 68 Joints at Week 52
    Description Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 68. A reduction in number of tender joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 15 106
    Mean (Standard Deviation) [percent change]
    -83.12
    (26.607)
    -80.44
    (41.226)
    23. Secondary Outcome
    Title Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
    Description Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of tender joints compared to baseline indicates improvement.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 139
    Baseline
    10.4
    (6.46)
    12.9
    (7.06)
    Change at Week 2
    -3.4
    (5.62)
    -2.4
    (5.63)
    Change at Week 4
    -3.9
    (5.80)
    -5.4
    (6.14)
    Change at Week 8
    -6.6
    (6.41)
    -6.4
    (6.94)
    Change at Week 12
    -6.0
    (6.71)
    -8.0
    (7.35)
    Change at Week 16
    -7.9
    (6.35)
    -8.2
    (7.05)
    Change at Week 20
    -8.5
    (6.59)
    -8.3
    (7.09)
    Change at Week 24
    -8.3
    (7.41)
    -9.3
    (7.53)
    Change at Week 28
    -8.7
    (6.26)
    -9.2
    (7.04)
    Change at Week 32
    -7.6
    (6.64)
    -10.1
    (6.76)
    Change at Week 36
    -9.4
    (6.25)
    -9.7
    (7.23)
    Change at Week 40
    -10.1
    (6.64)
    -10.3
    (6.74)
    Change at Week 44
    -9.7
    (6.46)
    -10.4
    (6.63)
    Change at Week 48
    -9.6
    (6.36)
    -10.5
    (6.70)
    Change at Week 52
    -9.4
    (7.15)
    -10.4
    (8.01)
    Change at early withdrawal
    -7.0
    (6.24)
    -3.3
    (7.46)
    24. Secondary Outcome
    Title Percent Change From Baseline in Total SJC on 66 Joints at Week 52
    Description Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 66. A reduction in number of swollen joints compared to baseline indicates improvement. The outcome is reported as the percent change from baseline to end of treatment (52 weeks).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 16 102
    Mean (Standard Deviation) [percent change]
    -89.31
    (20.059)
    -74.77
    (66.277)
    25. Secondary Outcome
    Title Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
    Description Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28. A reduction in number of swollen joints compared to baseline indicates improvement.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 139
    Baseline
    7.0
    (4.64)
    5.6
    (4.43)
    Change at Week 2
    -2.5
    (4.31)
    -0.8
    (3.95)
    Change at Week 4
    -4.2
    (3.79)
    -2.5
    (3.81)
    Change at Week 8
    -4.8
    (4.21)
    -3.2
    (4.40)
    Change at Week 12
    -4.2
    (4.37)
    -3.8
    (4.36)
    Change at Week 16
    -5.3
    (4.67)
    -3.9
    (4.41)
    Change at Week 20
    -5.6
    (5.08)
    -4.2
    (4.60)
    Change at Week 24
    -5.9
    (5.12)
    -4.7
    (4.21)
    Change at Week 28
    -6.4
    (4.90)
    -4.4
    (4.63)
    Change at Week 32
    -5.4
    (5.10)
    -4.8
    (4.37)
    Change at Week 36
    -6.5
    (4.57)
    -4.9
    (4.41)
    Change at Week 40
    -6.6
    (5.12)
    -5.0
    (4.82)
    Change at Week 44
    -6.6
    (5.28)
    -5.2
    (4.71)
    Change at Week 48
    -6.4
    (4.83)
    -5.0
    (4.48)
    Change at Week 52
    -6.3
    (4.81)
    -5.1
    (4.51)
    Change at early withdrawal
    -5.8
    (5.59)
    -1.7
    (4.43)
    26. Secondary Outcome
    Title Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    0
    0%
    5
    3.6%
    Week 2
    7
    33.3%
    18
    12.9%
    Week 4
    9
    42.9%
    30
    21.4%
    Week 8
    3
    14.3%
    25
    17.9%
    Week 12
    6
    28.6%
    23
    16.4%
    Week 16
    3
    14.3%
    20
    14.3%
    Week 20
    3
    14.3%
    15
    10.7%
    Week 24
    2
    9.5%
    15
    10.7%
    Week 28
    4
    19%
    15
    10.7%
    Week 32
    5
    23.8%
    14
    10%
    Week 36
    1
    4.8%
    14
    10%
    Week 40
    3
    14.3%
    14
    10%
    Week 44
    5
    23.8%
    10
    7.1%
    Week 48
    3
    14.3%
    12
    8.6%
    Week 52
    0
    0%
    11
    7.9%
    Early withdrawal
    2
    9.5%
    4
    2.9%
    27. Secondary Outcome
    Title Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6
    Description DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR <2.6 implied clinical remission.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    0
    0%
    3
    2.1%
    Week 2
    1
    4.8%
    15
    10.7%
    Week 4
    2
    9.5%
    34
    24.3%
    Week 8
    5
    23.8%
    53
    37.9%
    Week 12
    6
    28.6%
    66
    47.1%
    Week 16
    10
    47.6%
    72
    51.4%
    Week 20
    11
    52.4%
    75
    53.6%
    Week 24
    14
    66.7%
    76
    54.3%
    Week 28
    14
    66.7%
    73
    52.1%
    Week 32
    12
    57.1%
    80
    57.1%
    Week 36
    14
    66.7%
    80
    57.1%
    Week 40
    13
    61.9%
    81
    57.9%
    Week 44
    10
    47.6%
    80
    57.1%
    Week 48
    11
    52.4%
    78
    55.7%
    Week 52
    12
    57.1%
    80
    57.1%
    Early withdrawal
    3
    14.3%
    7
    5%
    28. Secondary Outcome
    Title Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation
    Description Results are reported for number of participants who had non-biologic DMARD/corticosteroid dose reductions and/or discontinuation by reasons for dose reductions or discontinuation (safety reasons, discomfort, lack of efficacy, other reasons, and unknown reasons). Participants may be included under more than one reason.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, at early withdrawal (up to Week 52), follow-up Week 4 (up to Week 56), and follow-up Week 8 (up to Week 60)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline: Safety
    0
    0%
    1
    0.7%
    Baseline: Discomfort
    0
    0%
    0
    0%
    Baseline: Lack of efficacy
    0
    0%
    1
    0.7%
    Baseline: Other
    0
    0%
    2
    1.4%
    Baseline: Unknown
    0
    0%
    0
    0%
    Week 2: Safety
    0
    0%
    4
    2.9%
    Week 2: Discomfort
    0
    0%
    0
    0%
    Week 2: Lack of efficacy
    0
    0%
    0
    0%
    Week 2: Other
    0
    0%
    7
    5%
    Week 2: Unknown
    0
    0%
    0
    0%
    Week 4: Safety
    0
    0%
    6
    4.3%
    Week 4: Discomfort
    0
    0%
    0
    0%
    Week 4: Lack of efficacy
    0
    0%
    1
    0.7%
    Week 4: Other
    1
    4.8%
    9
    6.4%
    Week 4: Unknown
    0
    0%
    1
    0.7%
    Week 8: Safety
    0
    0%
    8
    5.7%
    Week 8: Discomfort
    0
    0%
    0
    0%
    Week 8: Lack of efficacy
    0
    0%
    0
    0%
    Week 8: Other
    1
    4.8%
    13
    9.3%
    Week 8: Unknown
    0
    0%
    1
    0.7%
    Week 12: Safety
    0
    0%
    6
    4.3%
    Week 12: Discomfort 8
    0
    0%
    2
    1.4%
    Week 12: Lack of efficacy
    0
    0%
    0
    0%
    Week 12: Other
    2
    9.5%
    14
    10%
    Week 12: Unknown
    0
    0%
    0
    0%
    Week 16: Safety
    0
    0%
    7
    5%
    Week 16: Discomfort
    0
    0%
    0
    0%
    Week 16: Lack of efficacy
    0
    0%
    1
    0.7%
    Week 16: Other
    2
    9.5%
    13
    9.3%
    Week 16: Unknown
    0
    0%
    0
    0%
    Week 20: Safety
    0
    0%
    6
    4.3%
    Week 20: Discomfort
    0
    0%
    0
    0%
    Week 20: Lack of efficacy
    0
    0%
    0
    0%
    Week 20: Other
    2
    9.5%
    9
    6.4%
    Week 20: Unknown
    0
    0%
    1
    0.7%
    Week 24: Safety
    0
    0%
    5
    3.6%
    Week 24:Discomfort
    0
    0%
    0
    0%
    Week 24: Lack of efficacy
    0
    0%
    0
    0%
    Week 24: Other
    1
    4.8%
    13
    9.3%
    Week 24: Unknown
    0
    0%
    1
    0.7%
    Week 28: Safety
    0
    0%
    3
    2.1%
    Week 28: Discomfort
    0
    0%
    0
    0%
    Week 28: Lack of efficacy
    0
    0%
    1
    0.7%
    Week 28: Other
    1
    4.8%
    7
    5%
    Week 28: Unknown
    0
    0%
    0
    0%
    Week 32: Safety
    0
    0%
    4
    2.9%
    Week 32: Discomfort
    0
    0%
    0
    0%
    Week 32: Lack of efficacy
    0
    0%
    2
    1.4%
    Week 32: Other
    1
    4.8%
    11
    7.9%
    Week 32: Unknown
    0
    0%
    0
    0%
    Week 36: Safety
    0
    0%
    3
    2.1%
    Week 36: Discomfort
    0
    0%
    1
    0.7%
    Week 36: Lack of efficacy
    0
    0%
    0
    0%
    Week 36: Other
    2
    9.5%
    3
    2.1%
    Week 36: Unknown
    0
    0%
    0
    0%
    Week 40: Safety
    0
    0%
    4
    2.9%
    Week 40: Discomfort
    0
    0%
    1
    0.7%
    Week 40: Lack of efficacy
    0
    0%
    1
    0.7%
    Week 40: Other
    1
    4.8%
    1
    0.7%
    Week 40: Unknown
    0
    0%
    0
    0%
    Week 44: Safety
    0
    0%
    3
    2.1%
    Week 44: Discomfort
    0
    0%
    0
    0%
    Week 44: Lack of efficacy
    0
    0%
    0
    0%
    Week 44: Other
    0
    0%
    7
    5%
    Week 44: Unknown
    0
    0%
    0
    0%
    Week 48: Safety
    0
    0%
    3
    2.1%
    Week 48: Discomfort
    0
    0%
    0
    0%
    Week 48: Lack of efficacy
    0
    0%
    1
    0.7%
    Week 48: Other
    1
    4.8%
    3
    2.1%
    Week 48: Unknown
    0
    0%
    0
    0%
    Week 52: Safety
    0
    0%
    0
    0%
    Week 52: Discomfort
    0
    0%
    0
    0%
    Week 52: Lack of efficacy
    0
    0%
    0
    0%
    Week 52: Other
    0
    0%
    1
    0.7%
    Week 52: Unknown
    0
    0%
    0
    0%
    Early withdrawal: Safety
    0
    0%
    0
    0%
    Early withdrawal: Discomfort
    0
    0%
    0
    0%
    Early withdrawal: Lack of efficacy
    0
    0%
    0
    0%
    Early withdrawal: Other
    1
    4.8%
    8
    5.7%
    Early withdrawal: Unknown
    0
    0%
    0
    0%
    Follow-up Week 4: Safety
    0
    0%
    0
    0%
    Follow-up Week 4: Discomfort
    0
    0%
    0
    0%
    Follow-up Week 4: Lack of efficacy
    0
    0%
    0
    0%
    Follow-up Week 4: Other
    0
    0%
    2
    1.4%
    Follow-up Week 4: Unknown
    0
    0%
    1
    0.7%
    Follow-up Week 8: Safety
    0
    0%
    0
    0%
    Follow-up Week 8: Discomfort
    0
    0%
    0
    0%
    Follow-up Week 8: Lack of efficacy
    0
    0%
    0
    0%
    Follow-up Week 8: Other
    0
    0%
    0
    0%
    Follow-up Week 8: Unknown
    0
    0%
    0
    0%
    29. Secondary Outcome
    Title Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire
    Description Methotrexate adherence was determined from responses to the question 'Over the last 3 months you were prescribed 12 doses of methotrexate, how many (approximately) have you taken?' Adherence (%) was calculated as: (Approximate number of doses taken/12)*100.
    Time Frame Baseline, Weeks 12, 24, 36, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome. Results are provided for single arm as participants in "Tocilizumab Monotherapy" arm did not receive methotrexate.
    Arm/Group Title Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 97
    Baseline
    96.82
    (7.747)
    Week 12
    92.92
    (14.412)
    Week 24
    91.54
    (20.915)
    Week 36
    90.14
    (21.456)
    Week 52
    95.28
    (11.417)
    Early withdrawal
    90.69
    (18.367)
    30. Secondary Outcome
    Title Patient Global Assessment of Disease Activity VAS Score
    Description Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    59.6
    (26.94)
    62.3
    (20.72)
    Week 2
    50.3
    (24.01)
    54.5
    (22.12)
    Week 4
    46.4
    (26.43)
    42.3
    (23.22)
    Week 8
    35.8
    (24.73)
    36.2
    (24.43)
    Week 12
    41.3
    (27.67)
    32.1
    (23.91)
    Week 16
    29.6
    (21.59)
    29.2
    (22.55)
    Week 20
    25.7
    (23.77)
    29.9
    (22.99)
    Week 24
    23.8
    (19.55)
    26.6
    (21.92)
    Week 28
    23.2
    (16.47)
    26.7
    (23.12)
    Week 32
    24.0
    (17.81)
    24.3
    (21.66)
    Week 36
    24.1
    (19.13)
    22.3
    (21.86)
    Week 40
    22.5
    (19.31)
    21.4
    (20.81)
    Week 44
    22.7
    (20.62)
    22.0
    (22.83)
    Week 48
    22.9
    (23.31)
    18.9
    (20.57)
    Week 52
    20.6
    (18.96)
    21.4
    (23.07)
    Early withdrawal
    30.8
    (28.78)
    52.4
    (24.88)
    31. Secondary Outcome
    Title Patient Pain VAS Score
    Description This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS populations.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    50.5
    (23.78)
    57.5
    (21.06)
    Week 2
    46.1
    (22.43)
    51.1
    (22.58)
    Week 4
    47.0
    (26.69)
    42.4
    (23.80)
    Week 8
    37.8
    (25.75)
    35.3
    (24.30)
    Week 12
    40.9
    (29.56)
    30.8
    (23.29)
    Week 16
    29.7
    (20.83)
    26.8
    (22.61)
    Week 20
    27.6
    (25.48)
    28.6
    (23.74)
    Week 24
    29.9
    (22.76)
    25.2
    (22.16)
    Week 28
    24.8
    (19.15)
    25.6
    (23.18)
    Week 32
    25.1
    (17.92)
    22.6
    (21.30)
    Week 36
    29.6
    (20.03)
    22.1
    (21.68)
    Week 40
    27.6
    (22.70)
    20.9
    (21.24)
    Week 44
    26.7
    (24.25)
    20.0
    (21.26)
    Week 48
    28.6
    (28.98)
    17.6
    (19.66)
    Week 52
    22.4
    (19.70)
    19.0
    (19.83)
    Early withdrawal
    30.4
    (29.57)
    51.6
    (26.03)
    32. Secondary Outcome
    Title Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
    Description The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    1.806
    (0.5551)
    1.738
    (0.6406)
    Week 2
    1.558
    (0.7319)
    1.659
    (0.6210)
    Week 4
    1.616
    (0.7720)
    1.546
    (0.7351)
    Week 8
    1.508
    (0.7597)
    1.404
    (0.8115)
    Week 12
    1.488
    (0.9304)
    1.333
    (0.8272)
    Week 16
    1.351
    (0.9586)
    1.312
    (0.8621)
    Week 20
    1.409
    (0.9071)
    1.318
    (0.8608)
    Week 24
    1.330
    (0.8379)
    1.261
    (0.8915)
    Week 28
    1.330
    (0.9412)
    1.221
    (0.8730)
    Week 32
    1.351
    (0.8816)
    1.232
    (0.8870)
    Week 36
    1.432
    (0.9048)
    1.170
    (0.8757)
    Week 40
    1.479
    (0.8975)
    1.199
    (0.8908)
    Week 44
    1.442
    (0.9392)
    1.130
    (0.9206)
    Week 48
    1.361
    (0.9685)
    1.114
    (0.8815)
    Week 52
    1.338
    (0.9796)
    1.154
    (0.9187)
    Early withdrawal
    1.252
    (1.1232)
    1.756
    (0.7820)
    33. Secondary Outcome
    Title Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
    Description The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score).
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    18.4
    (11.14)
    24.3
    (11.55)
    Week 2
    23.1
    (12.37)
    27.9
    (11.03)
    Week 4
    25.1
    (12.28)
    30.7
    (12.10)
    Week 8
    30.2
    (11.58)
    32.8
    (11.91)
    Week 12
    28.4
    (11.71)
    33.7
    (11.85)
    Week 16
    31.3
    (13.80)
    34.0
    (12.53)
    Week 20
    33.2
    (13.57)
    34.1
    (12.05)
    Week 24
    33.8
    (15.28)
    35.3
    (10.98)
    Week 28
    32.9
    (12.06)
    35.5
    (11.59)
    Week 32
    34.1
    (12.68)
    36.2
    (11.32)
    Week 36
    30.3
    (13.62)
    36.8
    (11.48)
    Week 40
    31.7
    (12.87)
    37.1
    (11.69)
    Week 44
    31.0
    (14.02)
    37.2
    (11.75)
    Week 48
    31.6
    (14.63)
    37.9
    (11.73)
    Week 52
    33.4
    (14.17)
    38.1
    (11.16)
    Early withdrawal
    31.3
    (2.63)
    24.5
    (12.08)
    34. Secondary Outcome
    Title Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records
    Description A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.
    Time Frame Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    21
    100%
    137
    97.9%
    Week 2
    20
    95.2%
    126
    90%
    Week 4
    20
    95.2%
    132
    94.3%
    Week 8
    18
    85.7%
    124
    88.6%
    Week 12
    18
    85.7%
    121
    86.4%
    Week 16
    19
    90.5%
    120
    85.7%
    Week 20
    18
    85.7%
    114
    81.4%
    Week 24
    16
    76.2%
    107
    76.4%
    Week 28
    19
    90.5%
    112
    80%
    Week 32
    17
    81%
    111
    79.3%
    Week 36
    17
    81%
    105
    75%
    Week 40
    16
    76.2%
    104
    74.3%
    Week 44
    16
    76.2%
    102
    72.9%
    Week 48
    13
    61.9%
    107
    76.4%
    Week 52
    16
    76.2%
    98
    70%
    Early withdrawal
    4
    19%
    27
    19.3%
    35. Secondary Outcome
    Title Number of Participants With Anti-Tocilizumab Antibodies
    Description
    Time Frame Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    3
    14.3%
    6
    4.3%
    Week 12
    0
    0%
    Week 24
    0
    0%
    2
    1.4%
    Early withdrawal
    0
    0%
    0
    0%
    Follow-up visit
    0
    0%
    0
    0%
    36. Secondary Outcome
    Title Serum Levels of Tocilizumab
    Description
    Time Frame Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    0.0000
    (0.0000)
    0.0082
    (0.09619)
    Week 12
    35.3953
    (22.69069)
    40.2529
    (21.05801)
    Week 24
    53.0416
    (39.06367)
    43.9047
    (30.41603)
    Early withdrawal
    44.7160
    (38.81521)
    17.6160
    (22.92477)
    Follow-up visit
    0.0597
    (0.10335)
    2.3123
    (7.40931)
    37. Secondary Outcome
    Title Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)
    Description
    Time Frame Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)

    Outcome Measure Data

    Analysis Population Description
    FAS population.
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    Measure Participants 21 140
    Baseline
    43.63
    (10.947)
    42.40
    (12.087)
    Week 12
    577.42
    (175.649)
    548.70
    (131.079)
    Week 24
    602.25
    (158.541)
    521.07
    (160.464)
    Early withdrawal
    639.75
    (99.644)
    327.95
    (229.481)
    Follow-up visit
    132.23
    (93.048)
    125.07
    (211.038)

    Adverse Events

    Time Frame Baseline up to Week 60
    Adverse Event Reporting Description FAS population
    Arm/Group Title Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Arm/Group Description Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks. Participants received a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
    All Cause Mortality
    Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/21 (14.3%) 7/140 (5%)
    Cardiac disorders
    Atrial fibrillation 0/21 (0%) 1/140 (0.7%)
    Gastrointestinal disorders
    Vomiting 1/21 (4.8%) 0/140 (0%)
    Infections and infestations
    Arthritis bacterial 0/21 (0%) 1/140 (0.7%)
    Cellulitis 0/21 (0%) 1/140 (0.7%)
    Pneumonia 1/21 (4.8%) 0/140 (0%)
    Sinusitis 1/21 (4.8%) 0/140 (0%)
    Subcutaneous abscess 0/21 (0%) 1/140 (0.7%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/21 (0%) 1/140 (0.7%)
    Wound 1/21 (4.8%) 0/140 (0%)
    Musculoskeletal and connective tissue disorders
    Costochondritis 0/21 (0%) 1/140 (0.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer 1/21 (4.8%) 0/140 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary fibrosis 0/21 (0%) 1/140 (0.7%)
    Skin and subcutaneous tissue disorders
    Drug eruption 0/21 (0%) 1/140 (0.7%)
    Surgical and medical procedures
    Knee arthroplasty 1/21 (4.8%) 0/140 (0%)
    Other (Not Including Serious) Adverse Events
    Tocilizumab Monotherapy Tocilizumab in Combination With Methotrexate or Other DMARDs
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/21 (90.5%) 135/140 (96.4%)
    Blood and lymphatic system disorders
    Neutropenia 0/21 (0%) 14/140 (10%)
    Gastrointestinal disorders
    Diarrhoea 2/21 (9.5%) 32/140 (22.9%)
    Nausea 0/21 (0%) 21/140 (15%)
    Mouth ulceration 1/21 (4.8%) 18/140 (12.9%)
    Vomiting 2/21 (9.5%) 16/140 (11.4%)
    Abdominal pain 0/21 (0%) 7/140 (5%)
    General disorders
    Injection site bruising 3/21 (14.3%) 12/140 (8.6%)
    Fatigue 1/21 (4.8%) 12/140 (8.6%)
    Injection site erythema 1/21 (4.8%) 11/140 (7.9%)
    Influenza like illness 1/21 (4.8%) 8/140 (5.7%)
    Peripheral swelling 1/21 (4.8%) 8/140 (5.7%)
    Infections and infestations
    Nasopharyngitis 5/21 (23.8%) 33/140 (23.6%)
    Lower respiratory tract infection 6/21 (28.6%) 25/140 (17.9%)
    Upper respiratory tract infection 2/21 (9.5%) 20/140 (14.3%)
    Urinary tract infection 5/21 (23.8%) 16/140 (11.4%)
    Oral herpes 1/21 (4.8%) 10/140 (7.1%)
    Lower respiratory tract infection viral 2/21 (9.5%) 0/140 (0%)
    Injury, poisoning and procedural complications
    Contusion 2/21 (9.5%) 13/140 (9.3%)
    Fall 1/21 (4.8%) 14/140 (10%)
    Laceration 0/21 (0%) 7/140 (5%)
    Investigations
    Alanine aminotransferase increased 2/21 (9.5%) 31/140 (22.1%)
    Neutrophil count decreased 0/21 (0%) 13/140 (9.3%)
    Blood cholesterol increased 3/21 (14.3%) 5/140 (3.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/21 (4.8%) 12/140 (8.6%)
    Back pain 3/21 (14.3%) 10/140 (7.1%)
    Pain in extremity 0/21 (0%) 11/140 (7.9%)
    Rheumatoid arthritis 0/21 (0%) 11/140 (7.9%)
    Nervous system disorders
    Headache 4/21 (19%) 13/140 (9.3%)
    Dizziness 2/21 (9.5%) 8/140 (5.7%)
    Migraine 1/21 (4.8%) 7/140 (5%)
    Paraesthesia 2/21 (9.5%) 6/140 (4.3%)
    Lethargy 0/21 (0%) 7/140 (5%)
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain 3/21 (14.3%) 27/140 (19.3%)
    Cough 4/21 (19%) 21/140 (15%)
    Productive cough 2/21 (9.5%) 3/140 (2.1%)
    Skin and subcutaneous tissue disorders
    Rash 0/21 (0%) 18/140 (12.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02046603
    Other Study ID Numbers:
    • ML28641
    • 2013-000054-22
    First Posted:
    Jan 28, 2014
    Last Update Posted:
    Dec 7, 2018
    Last Verified:
    May 1, 2018