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

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Tocilizumab

• Registration Number: NCT02809833
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01
• Primary Completion: 2012-03
• Study Completion: 2012-03
• Study First Submitted: 2016-06-20
• Study First Submitted QC: 2016-06-20
• Study First Posted: 2016-06-22
• Status Verified: 2016-08
• Results First Submitted: 2016-08-30
• Results First Submitted QC: 2016-08-30
• Last Update Submitted: 2016-08-30
• Results First Posted: 2016-10-24
• Last Update Posted: 2016-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 850

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tocilizumab for RA in Routine Practice	Tocilizumab	Participants from routine clinical practice in Germany who are receiving tocilizumab for RA according to SmPC are eligible.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 12	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 16	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.
Percentage of Participants With Categorized Laboratory Data Available at Baseline	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.
Percentage of Participants With Categorized Laboratory Data Available at Week 24	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.
Percentage of Participants With Categorized Laboratory Data Available at Week 52	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 4	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 8	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 20	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 24	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 28	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 32	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 36	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 40	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 44	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 48	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.
Percentage of Participants With or Without Tocilizumab Dose Adjustment or Interruption at Week 52	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.
Percentage of Participants With Tocilizumab Dose Adjustments by Reason	Baseline to end of treatment (up to 12 months)	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.
28-Joint Disease Activity Score (DAS28) at Baseline	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.
Change in DAS28 From Baseline to Week 4	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.
Change in DAS28 From Baseline to Week 8	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.
Change in DAS28 From Baseline to Week 12	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.
Change in DAS28 From Baseline to Week 16	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.
Change in DAS28 From Baseline to Week 20	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.
Change in DAS28 From Baseline to Week 24	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.
Change in DAS28 From Baseline to Week 28	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.
Change in DAS28 From Baseline to Week 32	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.
Change in DAS28 From Baseline to Week 36	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.
Change in TJC From Baseline to Week 36	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.
Change in DAS28 From Baseline to Week 40	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.
Change in DAS28 From Baseline to Week 44	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.
Change in DAS28 From Baseline to Week 48	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.
Change in DAS28 From Baseline to Week 52	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.
TJC at Baseline	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.
Change in TJC From Baseline to Week 12	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.
Change in TJC From Baseline to Week 24	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.
Change in TJC From Baseline to Week 52	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.
SJC at Baseline	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.
Change in SJC From Baseline to Week 12	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.
Change in SJC From Baseline to Week 24	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.
Change in SJC From Baseline to Week 36	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.
Change in SJC From Baseline to Week 52	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.
VAS Score of Participant-Assessed Disease Activity at Baseline	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.
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 12	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.
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 24	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.
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 36	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.
Change in VAS Score of Participant-Assessed Disease Activity From Baseline to Week 52	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.
VAS Score of Physician-Assessed Disease Activity at Baseline	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.
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 12	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.
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 24	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.
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 36	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.
Change in VAS Score of Physician-Assessed Disease Activity From Baseline to Week 52	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.
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 4	Baseline to 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".
Percentage of Participants With EULAR Response at Week 12	Baseline to 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".
Percentage of Participants With EULAR Response at Week 24	Baseline to 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".
Percentage of Participants With EULAR Response at Week 36	Baseline to 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".
Percentage of Participants With Remission According to DAS28 at Baseline	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.
Percentage of Participants With EULAR Response at Week 52	Baseline to 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".
Percentage of Participants With Low Disease Activity Score (LDAS) According to DAS28 at Baseline	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.
Percentage of Participants With LDAS According to DAS28 at Week 12	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.
Percentage of Participants With LDAS According to DAS28 at Week 24	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.
Percentage of Participants With LDAS According to DAS28 at Week 36	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.
Percentage of Participants With LDAS According to DAS28 at Week 52	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.
Percentage of Participants With Remission According to DAS28 at Week 12	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.
Percentage of Participants With Remission According to DAS28 at Week 24	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.
Percentage of Participants With Remission According to DAS28 at Week 36	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.
Percentage of Participants With Remission According to DAS28 at Week 52	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.
Percentage of Participants With Minimum Clinically Important Improvement (MCII) According to DAS28 at Week 12	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. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 12.
Percentage of Participants With MCII According to DAS28 at Week 24	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. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 24.
Percentage of Participants With MCII According to DAS28 at Week 36	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. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 36.
Percentage of Participants With MCII According to DAS28 at Week 52	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. MCII was defined as DAS28 reduction of ≥1.2 points from Baseline to Week 52.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With AEs Considered Causally Related to Tocilizumab	Baseline to end of treatment (up to 12 months)	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.