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Trial record 26 of 117 for:    "Connective Tissue Disease" | "Methylprednisolone"

A Study of Glucocorticoid Use to Evaluate Systematic Methylprednisolone Reduction in Patients With Rheumatoid Arthritis on Background RoActemra/Actemra (Tocilizumab) (ACT-ALONE)

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ClinicalTrials.gov Identifier: NCT01219933
Recruitment Status : Completed
First Posted : October 13, 2010
Results First Posted : January 19, 2015
Last Update Posted : January 19, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: methylprednisolone
Drug: tocilizumab [RoActemra/Actemra]
Enrollment 68
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (IV) once every 4 weeks and methotrexate (MTX) 7.5 to 25 mg per week (mg/week; per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received an oral glucocorticoid (GC; no product/dose limitation) until low disease activity (LDA; defined as Disease Activity Score Based on 28-Joint Count and C-reactive protein [DAS28-CRP] less than or equal to [≤]3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to methylprednisolone (MP) tablets, by mouth (PO). MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be greater than or equal to [≥]1 mg and ≤20 mg per day [mg/day]), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment
Period Title: Overall Study
Started 68
Completed 30
Not Completed 38
Reason Not Completed
Adverse Event             8
No LDA reached             5
No LDA maintained             7
Lost to Follow-up             3
GC free             1
Withdrawal by Subject             5
Protocol Violation             8
Lack of Efficacy             1
Arm/Group Title Tocilizumab
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Baseline Participants 68
Hide Baseline Analysis Population Description
Safety observational (obs): all participants included in the study who were eligible for the study at Visit (V) 1.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 68 participants
58.0  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants
Female
47
  69.1%
Male
21
  30.9%
1.Primary Outcome
Title Median GC Dose Taken During the Noninterventional Phase
Hide Description During the noninterventional phase of the study participants received GC as prescribed by the physician. Doses of all GC administered are expressed as MP equivalents.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety obs population; n (number) equals (=) number of participants analyzed for a given parameter at a specified timepoint
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 68
Median (Full Range)
Unit of Measure: mg
Start dose V1 (n=68)
6
(2 to 40)
Start dose (V1) for Interventional phase (n=50)
6
(2 to 32)
Stop dose (V2; n=50)
4
(1 to 16)
Change from start to stop (n=50)
0
(-24 to 2)
Cumulative dose from V1 to V2 (n=45)
320
(58 to 2688)
2.Primary Outcome
Title Number of Participants With GC Switches During the Noninterventional Phase
Hide Description During the noninterventional phase of the study, once LDA was achieved, GC was switched to MP tablets.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety obs population; n=number of participants analyzed for a given parameter at a specified timepoint
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 50
Measure Type: Number
Unit of Measure: participants
0
3.Primary Outcome
Title Type of GC Taken at the End of the Noninterventional Phase
Hide Description During the noninterventional phase of the study participants received GC as prescribed by the physician.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety obs population; n=number of participants analyzed for a given parameter at a specified timepoint
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 50
Measure Type: Number
Unit of Measure: percentage of participants
MP 70.0
Prednisolone 28.0
Prednisone 2.0
4.Primary Outcome
Title Percentage of Participants in the Interventional Phase Who Achieved LDA and Discontinued Oral GC Within 20 Weeks
Hide Description The percentage of participants with rheumatoid arthritis (RA) with LDA was defined as DAS28 ≤3.2, able to discontinue oral GC within 20 weeks and at the latest at V8, confirmed at the Consolidation Visit without loss of clinical response defined as DAS28 (CRP) >3.2.
Time Frame Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), and 8 (12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population: all participants included in the interventional GC reduction phase of the study.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
58.1
(42.1 to 73.0)
5.Secondary Outcome
Title Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase
Hide Description DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and Patient's Global Assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day= LDA.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 68
Measure Type: Number
Unit of Measure: percentage of participants
72.1
6.Secondary Outcome
Title Percentage of Participants Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase
Hide Description DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <2.6 = remission.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 68
Measure Type: Number
Unit of Measure: percentage of participants
41.2
7.Secondary Outcome
Title Percentage of Participants With Erosions During the NonInterventional Phase
Hide Description In RA, the presence, number and size of bone erosions and the number of joints with erosions on conventional radiographs (CRs) are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: percentage of participants
V1 (n=57) 47.4
Between V1 and V2 (n=36) 41.7
8.Secondary Outcome
Title Number of Erosions During the NonInterventional Phase
Hide Description In RA, the presence, number, and size of bone erosions and the number of joints with erosions on CRs are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: erosions
V1 (n=11) 5.1  (6.0)
Between V1 and V2 (n=6) 3.2  (2.3)
9.Secondary Outcome
Title Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase
Hide Description RF is the auto antibody directed against immunoglobulin G (IgG) and its concentration is observed in human serum or plasma. RF value higher than 20 units per milliliter (U/mL) is considered positive.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 39
Measure Type: Number
Unit of Measure: percentage of participants
V1 (n=39) 56.4
Between V1 and V2 (n=21) 52.4
10.Secondary Outcome
Title Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase
Hide Description Anti-CCP antibodies are important markers of bone erosion in RA. Anti-CCP antibodies were classified as positive if >7 U/mL.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: percentage of participants
V1 (n=20) 75.0
Between V1 and V2 (n=6) 83.3
11.Secondary Outcome
Title Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase
Hide Description HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. Timepoint was V2, or before V2 for participants withdrawn before V2.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 66
Mean (Standard Deviation)
Unit of Measure: units on a scale
V1 (n=66) 1.7  (0.6)
V2 (n=61) 1.2  (0.7)
Change from V1 to V2 (n=60) -0.5  (0.6)
12.Secondary Outcome
Title DAS28-CRP During the Noninterventional Phase
Hide Description DAS28-CRP was calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-CRP values indicated in the Case Report Form (CRF) were recalculated by the data manager. The recalculated values were used in the statistical analyses.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 67
Mean (Standard Deviation)
Unit of Measure: units on a scale
V1 (n=67) 5.4  (1.0)
V2 (n=66) 2.9  (1.1)
Change from V1 to V2 (n=65) -2.5  (1.3)
13.Secondary Outcome
Title DAS28-ESR During the Noninterventional Phase
Hide Description DAS28-ESR was calculated from the SJC and TJC using the 28 joints count and ESR (millimeters per hour [mm/hr]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-ESR ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-ESR <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-ESR values indicated in the CRF were recalculated by the data manager. The recalculated values were used in the statistical analyses.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: units on a scale
V1 (n=62) 5.8  (1.0)
V2 (n=52) 3.3  (1.4)
Change from V1 to V2 (n=50) -2.7  (1.3)
14.Secondary Outcome
Title Clinical Disease Activity Index (CDAI) During the Noninterventional Phase
Hide Description The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and Physician Global Assessment (PGA) of disease assessed on 0-100 mm Visual analog scale (VAS); higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: units on a scale
V1 (n=62) 33.8  (12.2)
V2 (n=52) 14.6  (10.3)
Change from V1 to V2 (n=50) -20.4  (13.7)
15.Secondary Outcome
Title Median Time Interval Between V1 and V2
Hide Description The noninterventional phase was planned to last for a maximum of 6 months per participant. The time between V1 and V2 was measured in months.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 50
Median (Full Range)
Unit of Measure: months
2.3
(0.8 to 5.9)
16.Secondary Outcome
Title Median Dose of Tocilizumab During the Noninterventional Phase
Hide Description [Not Specified]
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 50
Median (Full Range)
Unit of Measure: mg/kg
8.0
(8.0 to 8.0)
17.Secondary Outcome
Title Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase
Hide Description The dose of tocilizumab could have been reduced from the recommended 8 mg/kg to 4 mg/kg in participants in the case of adverse events.
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 68
Measure Type: Number
Unit of Measure: participants
1
18.Secondary Outcome
Title Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase
Hide Description [Not Specified]
Time Frame V1 and V2 (up to 6 months after V1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 66
Measure Type: Number
Unit of Measure: percentage of participants
15.2
19.Secondary Outcome
Title Percentage of Participants Able to Start the GC Reduction Phase at V3
Hide Description All participants who maintained LDA (defined as DAS28-CRP ≤3.2) from V2 to V3 were included in the interventional phase for reduction of GC.
Time Frame V3 (7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int (intervention) run-in: all participants eligible to enter the interventional phase at V2 and who had taken at least 1 dose of MP.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
87.8
(75.2 to 95.4)
20.Secondary Outcome
Title Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9
Hide Description [Not Specified]
Time Frame V9 (24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; only those participants who completed the study at V9 were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
93.3
(77.9 to 99.2)
21.Secondary Outcome
Title Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9
Hide Description [Not Specified]
Time Frame V9 (24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; pnly those participants who completed the study at V9 were included in analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.3
(0.1 to 17.2)
22.Secondary Outcome
Title Time-Averaged GC Dose Changes During the Interventional Phase
Hide Description

Area Under the Curve (AUC) of GC dose during the interventional phase was determined using the trapezoidal method and was calculated as:

AUC = sigma(Ti+1 - Ti) x [(Di+1+Di)/2]

With Di=dosage at time Ti

It corresponds to the total GC dose received between Baseline (visit 3) and visit 9 and has been calculated only for the 30 patients achieving visit 9.

Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; only participants who completed the study were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: mg
341.8  (364.2)
23.Secondary Outcome
Title DAS28-CRP During the Interventional Phase
Hide Description DAS28-CRP was calculated from the SJC and TJC using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP) ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. DAS28-CRP values indicated in the CRF were recalculated by the data manager. The cumulative DAS28 (CRP) value (AUC method) was performed using the calculated DAS28. The recalculated values were used in the statistical analyses.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 42
Mean (Standard Deviation)
Unit of Measure: units on a scale
V3 (n=42) 2.2  (0.7)
CV (n=27) 2.3  (0.8)
Change from V3 to CV (n=27) 0.2  (0.8)
24.Secondary Outcome
Title HAQ-DI During the Interventional Phase
Hide Description HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. V3, CV, and the change from V3 to CV was determined.
Time Frame Visit 3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 41
Mean (Standard Deviation)
Unit of Measure: units on a scale
V3 (n=41) 1.0  (0.7)
CV (n=28) 0.8  (0.7)
Change from V3 to CV (n=26) 0.0  (0.4)
25.Secondary Outcome
Title VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase
Hide Description Physician's were asked to determine the overall GDA for each participant using a 100-mm VAS, where 0=no disease activity and 100=maximum disease activity. The physician marked the line corresponding to their assessment and the distance from the left edge was measured. V3, CV, and the change from V3 to CV was determined.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint. Only participants with values at both visits were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: mm
V3 (n=40) 16.6  (12.5)
CV (n=28) 16.7  (15.9)
Change from V3 to CV (n=26) 3.1  (15.4)
26.Secondary Outcome
Title VAS for Pain (VAS-Pain) During the Interventional Phase
Hide Description Participants were asked to mark the line corresponding to the intensity of their pain on a 100-mm VAS, where 0=no pain and 100=worst possible pain. The distance from the left edge was measured. Change = V3 mean minus CV mean.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint. Only participants with values at both visits were included in the analysis.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 43
Mean (Standard Deviation)
Unit of Measure: mm
V3 (n=43) 19.9  (16.5)
CV (n=28) 24.9  (19.0)
Change from V3 to CV (n=28) 6.9  (22.4)
27.Secondary Outcome
Title SJC and TJC During the Interventional Phase
Hide Description TJC and SJC were assessed for 28 joints. An assessment of 28 joints for swelling and tenderness was made. Joints were assessed and classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) by pressure and joint manipulation on physical examination for a total score range of 0-28. Higher scores indicated greater disease activity (tenderness/swelling). V3, CV, and the change from V3 to CV was determined.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 43
Mean (Standard Deviation)
Unit of Measure: joints
SJC V3 (n=43) 0.9  (1.3)
SJC CV (n=29) 0.4  (0.9)
SJC Change from V3 to CV (n=29) -0.3  (0.8)
TJC V3 (n=43) 0.9  (1.2)
TJC CV (n=29) 1.8  (2.7)
TJC Change from V3 to CV (n=29) 1.0  (2.6)
28.Secondary Outcome
Title Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase
Hide Description FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant’s response to the questions (with the exception of 2 negatively stated), the greater the participant’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant’s response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score). V3, CV, and the change from V3 to CV was determined.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
V3 (n=37) 37.5  (9.9)
CV (n=26) 35.6  (10.8)
Change from V3 to CV (n=22) 8.8  (19.0)
29.Secondary Outcome
Title Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase
Hide Description 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 “how would you rate your health in general now?” (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
MCS V3 (n=37) 47.0  (9.9)
MCS CV (n=26) 46.2  (9.0)
MCS: Change from V3 to CV (n=22) -4.4  (10.6)
PCS V3 (n=36) 42.5  (7.6)
PCS CV (n=26) 41.8  (8.8)
PCS: Change from V3 to CV (n=22) -2.1  (6.4)
30.Secondary Outcome
Title SF-36 Subscale Scores During the Interventional Phase
Hide Description SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 “how would you rate your health in general now?” (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; n=number of participants analyzed for the given parameter at the specified time point.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical functioning V3 (n=36) 41.52  (10.37)
Physical functioning CV (n=26) 41.92  (10.44)
Change in physical functioning V3 to CV (n=22) -1.80  (6.77)
Physical sub-score V3 (n=37) 40.61  (7.53)
Physical sub-score CV (n=26) 39.85  (8.23)
Change in physical sub-score V3 to CV (n=22) -2.79  (7.68)
Bodily pain V3 (n=37) 45.88  (8.35)
Bodily pain CV (n=26) 44.65  (9.70)
Change in bodily pain V3 to CV (n=22) -3.21  (8.67)
General health V3 (n=37) 43.11  (9.42)
General health CV (n=26) 40.82  (8.77)
Change in general health V3 to CV (n=22) -3.78  (7.35)
Vitality V3 (n=37) 50.51  (8.74)
Vitality CV (n=26) 48.91  (9.13)
Change in vitality V3 to CV (n=22) -4.37  (9.98)
Social functioning V3 (n=37) 45.42  (9.63)
Social functioning CV (n=26) 45.58  (9.29)
Change in social functioning V3 to CV (n=22) -2.73  (9.63)
Emotional sub-score V3 (n=37) 40.59  (9.98)
Emotional sub-score CV (n=26) 40.37  (10.53)
Change in emotional sub-score V3 to CV (n=22) -2.45  (10.29)
Mental health V3 (n=37) 47.14  (10.00)
Mental health CV (n=26) 45.94  (10.37)
Change in Mental health V3 to CV (n=22) -5.47  (10.98)
31.Secondary Outcome
Title CDAI Score During the Interventional Phase
Hide Description The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity. V3, CV, and the change from V3 to CV was determined.
Time Frame V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: units on a scale
V3 (n=40) 5.6  (3.8)
CV (n=27) 6.5  (5.4)
Change from V3 to CV (n=25) 1.4  (5.2)
32.Secondary Outcome
Title Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI
Hide Description The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission and >2.8 to 10=LDA.
Time Frame Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), 8 (12 months), and 9 (24 weeks after V3) or CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 41
Measure Type: Number
Unit of Measure: percentage of participants
V3 LDA (n=40) 85.0
V3 Remission (n=40) 27.5
V4 LDA (n=41) 82.9
V4 Remission (n=41) 39.0
V5 LDA (n=38) 81.6
V5 Remission (n=38) 47.4
V6 LDA (n=35) 71.4
V6 Remission (n=35) 37.1
V7 LDA (n=33) 75.8
V7 Remission (n=33) 33.3
V8 LDA (n=31) 80.6
V8 Remission (n=31) 38.7
V9 LDA (n=29) 69.0
V9 Remission (n=29) 31.0
CV LDA (n=27) 77.8
CV Remission (n=27) 33.3
33.Secondary Outcome
Title Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP
Hide Description DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-CRP ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day=LDA; DAS28 <2.6 = remission.
Time Frame Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), 8 (12 months), 9 (24 weeks after V3) or CV (4 weeks after GC-free status, maximum of 24 weeks after V3)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.
Arm/Group Title Tocilizumab
Hide Arm/Group Description:
Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week per investigator's discretion, or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: percentage of participants
V3 LDA (n=42) 90.5
V3 Remission (n=42) 73.8
V4 LDA (n=41) 85.4
V4 Remission (n=41) 73.2
V5 LDA (n=35) 88.6
V5 Remission (n=35) 71.4
V6 LDA (n=35) 82.9
V6 Remission (n=35) 62.9
V7 LDA (n=33) 90.9
V7 Remission (n=33) 57.6
V8 LDA (n=32) 87.5
V8 Remission (n=32) 62.5
V9 LDA (n=30) 73.3
V9 Remission (n=30) 56.7
CV LDA (n=27) 88.9
CV Remission (n=27) 59.3
Time Frame Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Noninterventional Phase Interventional Phase
Hide Arm/Group Description Participants received tocilizumab 8 mg/kg IV once every 4 weeks and MTX 7.5 to 25 mg/week according to local standard of care and at the investigator's discretion (or without MTX if intolerant) for up to 13 months. Participants also received GC (no product/dose limitation) until LDA (defined as DAS28-CRP ≤3.2), up to a maximum of 6 months. All participants who maintained LDA from V2 to V3 were included in the interventional phase for reduction of GC. Once LDA achieved, GC was switched to MP tablets, PO. MP dose determined by recalculating original GC dose to obtain an equivalent MP dose (had to be ≥1 mg and ≤20 mg/day), which was administered for 4 weeks. If LDA continued after 4 weeks, MP dose was reduced over the following 6 months per protocol-defined dose reduction schedule to reach 0 mg within 6 months for a maximum duration of 7 months of MP treatment.
All-Cause Mortality
Noninterventional Phase Interventional Phase
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Noninterventional Phase Interventional Phase
Affected / at Risk (%) Affected / at Risk (%)
Total   4/68 (5.88%)   1/43 (2.33%) 
Cardiac disorders     
Atrial fibrillation * 1  1/68 (1.47%)  0/43 (0.00%) 
Infections and infestations     
Cellulitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Osteitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Musculoskeletal and connective tissue disorders     
Neck pain * 1  1/68 (1.47%)  0/43 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer * 1  0/68 (0.00%)  1/43 (2.33%) 
Psychiatric disorders     
Attempted to commit suicide * 1  1/68 (1.47%)  0/43 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Noninterventional Phase Interventional Phase
Affected / at Risk (%) Affected / at Risk (%)
Total   36/68 (52.94%)   26/43 (60.47%) 
Blood and lymphatic system disorders     
Leukopenia * 1  1/68 (1.47%)  3/43 (6.98%) 
Thrombocytopenia * 1  1/68 (1.47%)  0/43 (0.00%) 
Neutropenia * 1  0/68 (0.00%)  1/43 (2.33%) 
Cardiac disorders     
Atrial fibrillation * 1  1/68 (1.47%)  0/43 (0.00%) 
Palpitations * 1  2/68 (2.94%)  0/43 (0.00%) 
Ear and labyrinth disorders     
Otosalpingitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Vertigo * 1  2/68 (2.94%)  1/43 (2.33%) 
Eye disorders     
Cataract * 1  1/68 (1.47%)  0/43 (0.00%) 
Conjunctivitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  2/68 (2.94%)  0/43 (0.00%) 
Diarrhoea * 1  2/68 (2.94%)  1/43 (2.33%) 
Dyspepsia * 1  1/68 (1.47%)  0/43 (0.00%) 
Gastritis * 1  2/68 (2.94%)  0/43 (0.00%) 
Nausea * 1  2/68 (2.94%)  0/43 (0.00%) 
Umbilical hernia * 1  1/68 (1.47%)  0/43 (0.00%) 
Vomiting * 1  1/68 (1.47%)  1/43 (2.33%) 
Abdominal pain upper * 1  0/68 (0.00%)  1/43 (2.33%) 
Diverticulum intestinal * 1  0/68 (0.00%)  1/43 (2.33%) 
General disorders     
Fatigue * 1  4/68 (5.88%)  0/43 (0.00%) 
Oedema peripheral * 1  0/68 (0.00%)  3/43 (6.98%) 
Asthenia * 1  1/68 (1.47%)  0/43 (0.00%) 
Face oedema * 1  1/68 (1.47%)  0/43 (0.00%) 
Pain * 1  0/68 (0.00%)  2/43 (4.65%) 
Pyrexia * 1  1/68 (1.47%)  1/43 (2.33%) 
Influenza like illness * 1  1/68 (1.47%)  0/43 (0.00%) 
Local swelling * 1  1/68 (1.47%)  0/43 (0.00%) 
Hepatobiliary disorders     
Hepatocellular injury * 1  1/68 (1.47%)  0/43 (0.00%) 
Infections and infestations     
Bronchitis * 1  6/68 (8.82%)  3/43 (6.98%) 
Body tinea * 1  0/68 (0.00%)  1/43 (2.33%) 
Arthritis infective * 1  1/68 (1.47%)  0/43 (0.00%) 
Cellulitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Cystitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Gastroenteritis * 1  1/68 (1.47%)  0/43 (0.00%) 
Lung infection * 1  1/68 (1.47%)  0/43 (0.00%) 
Pharyngitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Rhinitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Sinusitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Tinea pedis * 1  1/68 (1.47%)  0/43 (0.00%) 
Upper respiratory tract infection * 1  1/68 (1.47%)  0/43 (0.00%) 
Urinary tract infection * 1  1/68 (1.47%)  0/43 (0.00%) 
Vulvovaginal mycotic infection * 1  1/68 (1.47%)  0/43 (0.00%) 
Erysipelas * 1  0/68 (0.00%)  1/43 (2.33%) 
Herpes virus infection * 1  0/68 (0.00%)  1/43 (2.33%) 
Nasopharyngitis * 1  0/68 (0.00%)  1/43 (2.33%) 
Bronchopneumonia * 1  0/68 (0.00%)  1/43 (2.33%) 
Ear infection * 1  0/68 (0.00%)  1/43 (2.33%) 
Infection * 1  0/68 (0.00%)  1/43 (2.33%) 
Laryngitis * 1  0/68 (0.00%)  2/43 (4.65%) 
Injury, poisoning and procedural complications     
Wound * 1  1/68 (1.47%)  0/43 (0.00%) 
Spinal fracture * 1  0/68 (0.00%)  1/43 (2.33%) 
Investigations     
Alanine aminotransferase increased * 1  1/68 (1.47%)  0/43 (0.00%) 
Blood bilirubin increased * 1  1/68 (1.47%)  0/43 (0.00%) 
Hepatic enzyme increased * 1  1/68 (1.47%)  0/43 (0.00%) 
Weight increased * 1  0/68 (0.00%)  1/43 (2.33%) 
Metabolism and nutrition disorders     
Hypercholesterolaemia * 1  5/68 (7.35%)  1/43 (2.33%) 
Hyperglycaemia * 1  1/68 (1.47%)  0/43 (0.00%) 
Folate deficiency * 1  0/68 (0.00%)  1/43 (2.33%) 
Glucose tolerance impaired * 1  0/68 (0.00%)  1/43 (2.33%) 
Hypertriglyceridaemia * 1  0/68 (0.00%)  1/43 (2.33%) 
Vitamin D deficiency * 1  0/68 (0.00%)  1/43 (2.33%) 
Diabetes mellitus * 1  0/68 (0.00%)  1/43 (2.33%) 
Hyperlipidaemia * 1  0/68 (0.00%)  1/43 (2.33%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/68 (1.47%)  3/43 (6.98%) 
Arthralgia * 1  1/68 (1.47%)  1/43 (2.33%) 
Muscle spasms * 1  2/68 (2.94%)  1/43 (2.33%) 
Neck pain * 1  2/68 (2.94%)  1/43 (2.33%) 
Osteitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Osteoarthritis * 1  1/68 (1.47%)  0/43 (0.00%) 
Osteoporosis * 1  1/68 (1.47%)  0/43 (0.00%) 
Rheumatoid arthritis * 1  1/68 (1.47%)  0/43 (0.00%) 
Tendonitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Tenosynovitis * 1  1/68 (1.47%)  0/43 (0.00%) 
Musculoskeletal pain * 1  0/68 (0.00%)  1/43 (2.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma * 1  0/68 (0.00%)  1/43 (2.33%) 
Breast cancer * 1  0/68 (0.00%)  1/43 (2.33%) 
Nervous system disorders     
Headache * 1  3/68 (4.41%)  0/43 (0.00%) 
Presyncope * 1  0/68 (0.00%)  1/43 (2.33%) 
Dizziness * 1  0/68 (0.00%)  1/43 (2.33%) 
Psychiatric disorders     
Anxiety * 1  2/68 (2.94%)  1/43 (2.33%) 
Depression * 1  1/68 (1.47%)  0/43 (0.00%) 
Insomnia * 1  1/68 (1.47%)  1/43 (2.33%) 
Suicide attempt * 1  1/68 (1.47%)  0/43 (0.00%) 
Renal and urinary disorders     
Renal cyst * 1  1/68 (1.47%)  0/43 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  3/68 (4.41%)  2/43 (4.65%) 
Oropharyngeal pain * 1  1/68 (1.47%)  1/43 (2.33%) 
Rhinorrhoea * 1  0/68 (0.00%)  2/43 (4.65%) 
Sneezing * 1  0/68 (0.00%)  1/43 (2.33%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  1/68 (1.47%)  1/43 (2.33%) 
Pruritus * 1  2/68 (2.94%)  1/43 (2.33%) 
Psoriasis * 1  1/68 (1.47%)  0/43 (0.00%) 
Rash * 1  1/68 (1.47%)  1/43 (2.33%) 
Skin exfoliation * 1  1/68 (1.47%)  0/43 (0.00%) 
Skin reaction * 1  1/68 (1.47%)  0/43 (0.00%) 
Acne * 1  0/68 (0.00%)  1/43 (2.33%) 
Surgical and medical procedures     
Hip surgery * 1  1/68 (1.47%)  0/43 (0.00%) 
Skin neoplasm excision * 1  0/68 (0.00%)  1/43 (2.33%) 
Surgery * 1  0/68 (0.00%)  1/43 (2.33%) 
Vascular disorders     
Hypertension * 1  1/68 (1.47%)  0/43 (0.00%) 
Hot flush * 1  0/68 (0.00%)  1/43 (2.33%) 
Phlebitis * 1  0/68 (0.00%)  1/43 (2.33%) 
Rheumatoid vasculitis * 1  0/68 (0.00%)  1/43 (2.33%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann- LaRoche
Phone: 1-800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01219933     History of Changes
Other Study ID Numbers: ML25252
2010-019694-15
First Submitted: October 11, 2010
First Posted: October 13, 2010
Results First Submitted: August 26, 2014
Results First Posted: January 19, 2015
Last Update Posted: January 19, 2015