Use of Tocilizumab for Rheumatoid Arthritis (RA) in Daily Routine

Tocilizumab for the Treatment of Rheumatoid Arthritis: Findings on The Use of Tocilizumab in Daily Clinical Routine

This prospective, multicenter, non-interventional study will enroll participants from routine clinical practice in Germany who are receiving tocilizumab for RA. The objective of the study is systematic collection of data on use of tocilizumab in daily routine with special emphasis on treatment decision by the prescriber, compliance with Summary of Product Characteristics (SmPC), and documentation of relevant activity scores and adverse drug reactions (ADRs). The maximum observation period will be 12 months per participant.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tocilizumab

• Study Type: Observational
• Enrollment (Actual): 850

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants from routine clinical practice in Germany who are receiving tocilizumab for RA according to SmPC are eligible.

Description

Inclusion Criteria:

• Moderate to severe RA
• Tocilizumab indicated in accordance with SmPC and chosen by the treating physician in advance of the study

Exclusion Criteria:

• None specified

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tocilizumab for RA in Routine Practice; Participants from routine clinical practice in Germany who are receiving tocilizumab for RA according to SmPC are eligible.	Drug: Tocilizumab; Tocilizumab must be selected by the treating physician in advance of the study and will be not provided by the Sponsor. The dose/regimen are at the discretion of the prescriber. However, tocilizumab in the SmPC is specified as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion at 4-week intervals.; Other Names: Actemra/RoActemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Categorized Laboratory Data Available at Baseline	SmPC recommendations were specified in the collection of routine laboratory samples for alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), absolute neutrophil count (ANC), and low platelet count to guide dose decisions. Laboratory values for ALAT and ASAT were to be categorized in reference to the institution-specific upper limit of normal (ULN). Laboratory values for ANC and platelet count were to be categorized in reference to a normal range outlined in the SmPC. This range was 0.5 to 1 × 10^9 cells per liter (cells/L) for ANC and 50 to 100 × 10^3 cells per microliter (cells/μL) for platelet count. The percentage of participants with greater than or equal to (≥) 1 documented/evaluable laboratory value at Baseline was reported, along with the percentage of participants with categorized laboratory data available for each individual parameter.	Baseline
Percentage of Participants With Categorized Laboratory Data Available at Week 24	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and low platelet count to guide dose decisions. Laboratory values for ALAT and ASAT were to be categorized in reference to the institution-specific ULN. Laboratory values for ANC and platelet count were to be categorized in reference to a normal range outlined in the SmPC. This range was 0.5 to 1 × 10^9 cells/L for ANC and 50 to 100 × 10^3 cells/μL for platelet count. The percentage of participants with ≥1 documented/evaluable laboratory value at Week 24 was reported, along with the percentage of participants with categorized laboratory data available for each individual parameter.	Week 24
Percentage of Participants With Categorized Laboratory Data Available at Week 52	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and low platelet count to guide dose decisions. Laboratory values for ALAT and ASAT were to be categorized in reference to the institution-specific ULN. Laboratory values for ANC and platelet count were to be categorized in reference to a normal range outlined in the SmPC. This range was 0.5 to 1 × 10^9 cells/L for ANC and 50 to 100 × 10^3 cells/μL for platelet count. The percentage of participants with ≥1 documented/evaluable laboratory value at Week 52 was reported, along with the percentage of participants with categorized laboratory data available for each individual parameter.	Week 52
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 4	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values greater than (>) 1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC less than (<) 0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 4.	Week 4
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 8	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 8.	Week 8
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 12	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 12.	Week 12
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 16	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 16.	Week 16
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 20	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 20.	Week 20
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 24	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 24.	Week 24
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 28	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 28.	Week 28
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 32	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 32.	Week 32
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 36	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 36.	Week 36
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 40	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 40.	Week 40
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 44	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 44.	Week 44
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 48	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 48.	Week 48
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 52	SmPC recommendations were specified in the collection of routine laboratory samples for ALAT, ASAT, ANC, and platelet count to guide dose decisions. Dose adjustment was recommended in response to ALAT/ASAT values >1 to 3 × ULN. Dose interruption was recommended in response to ALAT/ASAT values >3 to 5 × ULN, ANC of 0.5 to 1 × 10^9 cells/L, or platelet count of 50 to 100 × 10^3 cells/μL, until the values returned to acceptable ranges as per the SmPC. Discontinuation of tocilizumab was recommended for any ALAT/ASAT values >5 × ULN, ANC <0.5 × 10^9 cells/L, or platelet count <50 × 10^3 cells/μL. The percentage of participants from each laboratory value category with ("Yes") or without ("No") tocilizumab dose adjustment or interruption was reported at Week 52.	Week 52
Percentage of Participants With Tocilizumab Dose Adjustments by Reason	The percentage of participants with any tocilizumab dose adjustment during the study was reported among all reasons given for tocilizumab dose adjustments, as provided in the CRF. The sum of all reasons may add up to >100 percent (%) because more than one reason could be given for each dose change. In the table presented, "Other Reasons" refers to any reason other than those specified in categories. Similarly, "Other Laboratory Change" refers to a change in any laboratory parameter other than those specified in categories.	Baseline to end of treatment (up to 12 months)
28-Joint Disease Activity Score (DAS28) at Baseline	The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), and general health according to 100-millimeter (mm) Visual Analog Scale (VAS). 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in millimeters per hour (mm/h). DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The score at Baseline was reported.	Baseline
Change in DAS28 From Baseline to Week 4	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 4 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 4
Change in DAS28 From Baseline to Week 8	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 8 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 8
Change in DAS28 From Baseline to Week 12	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 12 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 12
Change in DAS28 From Baseline to Week 16	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 16 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 16
Change in DAS28 From Baseline to Week 20	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 20 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 20
Change in DAS28 From Baseline to Week 24	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 24 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 24
Change in DAS28 From Baseline to Week 28	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 28 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 28
Change in DAS28 From Baseline to Week 32	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 32 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 32
Change in DAS28 From Baseline to Week 36	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 36 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 36
Change in DAS28 From Baseline to Week 40	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 40 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 40
Change in DAS28 From Baseline to Week 44	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 44 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 44
Change in DAS28 From Baseline to Week 48	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 48 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 48
Change in DAS28 From Baseline to Week 52	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 52 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 52
TJC at Baseline	A total of 28 joints were assessed for tenderness. The number of tender joints at Baseline was reported and could range from 0 to 28, where higher values represented more tender joints.	Baseline
Change in TJC From Baseline to Week 12	A total of 28 joints were assessed for tenderness. The number of tender joints could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to Week 12 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 12
Change in TJC From Baseline to Week 24	A total of 28 joints were assessed for tenderness. The number of tender joints could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to Week 24 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 24
Change in TJC From Baseline to Week 36	A total of 28 joints were assessed for tenderness. The number of tender joints could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to Week 36 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 36
Change in TJC From Baseline to Week 52	A total of 28 joints were assessed for tenderness. The number of tender joints could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to Week 52 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 52
SJC at Baseline	A total of 28 joints were assessed for swollenness. The number of swollen joints at Baseline was reported and could range from 0 to 28, where higher values represented more swollen joints.	Baseline
Change in SJC From Baseline to Week 12	A total of 28 joints were assessed for swollenness. The number of swollen joints could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to Week 12 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 12
Change in SJC From Baseline to Week 24	A total of 28 joints were assessed for swollenness. The number of swollen joints could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to Week 24 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 24
Change in SJC From Baseline to Week 36	A total of 28 joints were assessed for swollenness. The number of swollen joints could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to Week 36 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 36
Change in SJC From Baseline to Week 52	A total of 28 joints were assessed for swollenness. The number of swollen joints could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to Week 52 was reported, where negative changes indicated an improvement in disease activity.	Baseline to Week 52
VAS Score of Participant-Assessed Disease Activity at Baseline	Participant-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The VAS score at Baseline was reported.	Baseline
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 12	Participant-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 12 was reported, where negative changes indicated a decrease in participant-assessed disease activity.	Baseline to Week 12
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 24	Participant-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 24 was reported, where negative changes indicated a decrease in participant-assessed disease activity.	Baseline to Week 24
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 36	Participant-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 36 was reported, where negative changes indicated a decrease in participant-assessed disease activity.	Baseline to Week 36
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 52	Participant-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 52 was reported, where negative changes indicated a decrease in participant-assessed disease activity.	Baseline to Week 52
VAS Score of Physician-Assessed Disease Activity at Baseline	Physician-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The VAS score at Baseline was reported.	Baseline
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 12	Physician-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 12 was reported, where negative changes indicated a decrease in physician-assessed disease activity.	Baseline to Week 12
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 24	Physician-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 24 was reported, where negative changes indicated a decrease in physician-assessed disease activity.	Baseline to Week 24
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 36	Physician-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 36 was reported, where negative changes indicated a decrease in physician-assessed disease activity.	Baseline to Week 36
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 52	Physician-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's evaluation of disease activity. Higher scores corresponded to increased disease activity (0 mm = no disease activity and 100 mm = maximum disease activity). The change from Baseline to Week 52 was reported, where negative changes indicated a decrease in physician-assessed disease activity.	Baseline to Week 52
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 4	Response was determined using EULAR criteria based upon DAS28 absolute scores at the Week 4 visit and the DAS28 change from Baseline to Week 4. Participants with a score less than or equal to (≤) 3.2 and reduction of >1.2 points were assessed as having a "Good" response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a "Moderate" response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as non-responders with response recorded as "No Improvement".	Baseline to Week 4
Percentage of Participants With EULAR Response at Week 12	Response was determined using EULAR criteria based upon DAS28 absolute scores at the Week 12 visit and the DAS28 change from Baseline to Week 12. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a "Good" response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a "Moderate" response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as non-responders with response recorded as "No Improvement".	Baseline to Week 12
Percentage of Participants With EULAR Response at Week 24	Response was determined using EULAR criteria based upon DAS28 absolute scores at the Week 24 visit and the DAS28 change from Baseline to Week 24. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a "Good" response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a "Moderate" response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as non-responders with response recorded as "No Improvement".	Baseline to Week 24
Percentage of Participants With EULAR Response at Week 36	Response was determined using EULAR criteria based upon DAS28 absolute scores at the Week 36 visit and the DAS28 change from Baseline to Week 36. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a "Good" response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a "Moderate" response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as non-responders with response recorded as "No Improvement".	Baseline to Week 36
Percentage of Participants With EULAR Response at Week 52	Response was determined using EULAR criteria based upon DAS28 absolute scores at the Week 52 visit and the DAS28 change from Baseline to Week 52. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a "Good" response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a "Moderate" response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as non-responders with response recorded as "No Improvement".	Baseline to Week 52
Percentage of Participants With Low Disease Activity Score (LDAS) According to DAS28 at Baseline	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. LDAS was defined as a DAS28 score ≤3.2 at Baseline.	Baseline
Percentage of Participants With LDAS According to DAS28 at Week 12	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. LDAS was defined as a DAS28 score ≤3.2 at Week 12.	Week 12
Percentage of Participants With LDAS According to DAS28 at Week 24	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. LDAS was defined as a DAS28 score ≤3.2 at Week 24.	Week 24
Percentage of Participants With LDAS According to DAS28 at Week 36	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. LDAS was defined as a DAS28 score ≤3.2 at Week 36.	Week 36
Percentage of Participants With LDAS According to DAS28 at Week 52	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. LDAS was defined as a DAS28 score ≤3.2 at Week 52.	Week 52
Percentage of Participants With Remission According to DAS28 at Baseline	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. Remission was defined as a DAS28 score <2.6 at Baseline.	Baseline
Percentage of Participants With Remission According to DAS28 at Week 12	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. Remission was defined as a DAS28 score <2.6 at Week 12.	Week 12
Percentage of Participants With Remission According to DAS28 at Week 24	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. Remission was defined as a DAS28 score <2.6 at Week 24.	Week 24
Percentage of Participants With Remission According to DAS28 at Week 36	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. Remission was defined as a DAS28 score <2.6 at Week 36.	Week 36
Percentage of Participants With Remission According to DAS28 at Week 52	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. Remission was defined as a DAS28 score <2.6 at Week 52.	Week 52
Percentage of Participants With Minimum Clinically Important Improvement (MCII) According to DAS28 at Week 12	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 12.	Baseline to Week 12
Percentage of Participants With MCII According to DAS28 at Week 24	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 24.	Baseline to Week 24
Percentage of Participants With MCII According to DAS28 at Week 36	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 36.	Baseline to Week 36
Percentage of Participants With MCII According to DAS28 at Week 52	The DAS28 was derived from assessments of ESR, TJC, SJC, and general health according to 100-mm VAS. 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]. TJC was defined as the number of tender joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28 scores could range from 0 to 10, where higher scores represented higher disease activity. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 52.	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With AEs Considered Causally Related to Tocilizumab	An AE was defined as any unfavorable and unintended sign, symptom, or disease associated with the use of tocilizumab. Worsened pre-existing conditions and laboratory or clinical tests that resulted in change or discontinuation of treatment were reported as AEs. The percentage of participants with treatment-related AEs (also known as adverse drug reactions) was reported as a separate endpoint and included both serious and non-serious AEs. Those AEs with a causal relationship reported as "definite", "probably", "possible", or "unlikely" were considered to be related to tocilizumab. If the causal relationship was reported as "unrelated", the AE was considered not related to tocilizumab treatment. Terms were reported verbatim as coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 12.0. The most common treatment-related AEs were reported, using those from the 10 highest incidence rate levels.	Baseline to end of treatment (up to 12 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: June 20, 2016
• First Posted (ESTIMATE): June 22, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 24, 2016
• Last Update Submitted That Met QC Criteria: August 30, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: ML22734