Trial Outcomes & Findings for A Study of Glucocorticoid Use to Evaluate Systematic Methylprednisolone Reduction in Patients With Rheumatoid Arthritis on Background RoActemra/Actemra (Tocilizumab) (ACT-ALONE) (NCT NCT01219933)

NCT ID: NCT01219933

Last Updated: 2015-01-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

68 participants

Primary outcome timeframe

V1 and V2 (up to 6 months after V1)

Results posted on

2015-01-19

Participant Flow

Participant milestones

Participant milestones
Measure	Tocilizumab 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
Overall Study STARTED	68
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab 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
Overall Study Adverse Event	8
Overall Study No LDA reached	5
Overall Study No LDA maintained	7
Overall Study Lost to Follow-up	3
Overall Study GC free	1
Overall Study Withdrawal by Subject	5
Overall Study Protocol Violation	8
Overall Study Lack of Efficacy	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab n=68 Participants 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.
Age, Continuous	58.0 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety obs population; n (number) equals (=) number of participants analyzed for a given parameter at a specified timepoint

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=68 Participants 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.
Median GC Dose Taken During the Noninterventional Phase Cumulative dose from V1 to V2 (n=45)	320 mg Interval 58.0 to 2688.0
Median GC Dose Taken During the Noninterventional Phase Start dose V1 (n=68)	6 mg Interval 2.0 to 40.0
Median GC Dose Taken During the Noninterventional Phase Start dose (V1) for Interventional phase (n=50)	6 mg Interval 2.0 to 32.0
Median GC Dose Taken During the Noninterventional Phase Stop dose (V2; n=50)	4 mg Interval 1.0 to 16.0
Median GC Dose Taken During the Noninterventional Phase Change from start to stop (n=50)	0 mg Interval -24.0 to 2.0

PRIMARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety obs population; n=number of participants analyzed for a given parameter at a specified timepoint

During the noninterventional phase of the study, once LDA was achieved, GC was switched to MP tablets.

Outcome measures

Outcome measures
Measure	Tocilizumab n=50 Participants 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.
Number of Participants With GC Switches During the Noninterventional Phase	0 participants

PRIMARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety obs population; n=number of participants analyzed for a given parameter at a specified timepoint

During the noninterventional phase of the study participants received GC as prescribed by the physician.

Outcome measures

Outcome measures
Measure	Tocilizumab n=50 Participants 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.
Type of GC Taken at the End of the Noninterventional Phase MP	70.0 percentage of participants
Type of GC Taken at the End of the Noninterventional Phase Prednisolone	28.0 percentage of participants
Type of GC Taken at the End of the Noninterventional Phase Prednisone	2.0 percentage of participants

PRIMARY outcome

Timeframe: Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), and 8 (12 months)

Population: Intent-to-Treat (ITT) population: all participants included in the interventional GC reduction phase of the study.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=43 Participants 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.
Percentage of Participants in the Interventional Phase Who Achieved LDA and Discontinued Oral GC Within 20 Weeks	58.1 percentage of participants Interval 42.1 to 73.0

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=68 Participants 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.
Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase	72.1 percentage of participants

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs population

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=68 Participants 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.
Percentage of Participants Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase	41.2 percentage of participants

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=57 Participants 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.
Percentage of Participants With Erosions During the NonInterventional Phase V1 (n=57)	47.4 percentage of participants
Percentage of Participants With Erosions During the NonInterventional Phase Between V1 and V2 (n=36)	41.7 percentage of participants

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=11 Participants 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.
Number of Erosions During the NonInterventional Phase V1 (n=11)	5.1 erosions Standard Deviation 6.0
Number of Erosions During the NonInterventional Phase Between V1 and V2 (n=6)	3.2 erosions Standard Deviation 2.3

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=39 Participants 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.
Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase V1 (n=39)	56.4 percentage of participants
Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase Between V1 and V2 (n=21)	52.4 percentage of participants

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

Anti-CCP antibodies are important markers of bone erosion in RA. Anti-CCP antibodies were classified as positive if \>7 U/mL.

Outcome measures

Outcome measures
Measure	Tocilizumab n=20 Participants 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.
Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase V1 (n=20)	75.0 percentage of participants
Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase Between V1 and V2 (n=6)	83.3 percentage of participants

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=66 Participants 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.
Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase V1 (n=66)	1.7 units on a scale Standard Deviation 0.6
Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase V2 (n=61)	1.2 units on a scale Standard Deviation 0.7
Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase Change from V1 to V2 (n=60)	-0.5 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=67 Participants 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.
DAS28-CRP During the Noninterventional Phase V1 (n=67)	5.4 units on a scale Standard Deviation 1.0
DAS28-CRP During the Noninterventional Phase V2 (n=66)	2.9 units on a scale Standard Deviation 1.1
DAS28-CRP During the Noninterventional Phase Change from V1 to V2 (n=65)	-2.5 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=62 Participants 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.
DAS28-ESR During the Noninterventional Phase V1 (n=62)	5.8 units on a scale Standard Deviation 1.0
DAS28-ESR During the Noninterventional Phase V2 (n=52)	3.3 units on a scale Standard Deviation 1.4
DAS28-ESR During the Noninterventional Phase Change from V1 to V2 (n=50)	-2.7 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=62 Participants 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.
Clinical Disease Activity Index (CDAI) During the Noninterventional Phase V1 (n=62)	33.8 units on a scale Standard Deviation 12.2
Clinical Disease Activity Index (CDAI) During the Noninterventional Phase V2 (n=52)	14.6 units on a scale Standard Deviation 10.3
Clinical Disease Activity Index (CDAI) During the Noninterventional Phase Change from V1 to V2 (n=50)	-20.4 units on a scale Standard Deviation 13.7

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=50 Participants 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.
Median Time Interval Between V1 and V2	2.3 months Interval 0.8 to 5.9

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population

Outcome measures

Outcome measures
Measure	Tocilizumab n=50 Participants 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.
Median Dose of Tocilizumab During the Noninterventional Phase	8.0 mg/kg Interval 8.0 to 8.0

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=68 Participants 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.
Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase	1 participants

SECONDARY outcome

Timeframe: V1 and V2 (up to 6 months after V1)

Population: Safety Obs Population

Outcome measures

Outcome measures
Measure	Tocilizumab n=66 Participants 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.
Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase	15.2 percentage of participants

SECONDARY outcome

Timeframe: V3 (7 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=49 Participants 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.
Percentage of Participants Able to Start the GC Reduction Phase at V3	87.8 percentage of participants Interval 75.2 to 95.4

SECONDARY outcome

Timeframe: V9 (24 weeks after V3)

Population: Safety Int run-in; only those participants who completed the study at V9 were included in the analysis.

Outcome measures

Outcome measures
Measure	Tocilizumab n=30 Participants 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.
Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9	93.3 percentage of participants Interval 77.9 to 99.2

SECONDARY outcome

Timeframe: V9 (24 weeks after V3)

Population: Safety Int run-in; pnly those participants who completed the study at V9 were included in analysis.

Outcome measures

Outcome measures
Measure	Tocilizumab n=30 Participants 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.
Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9	3.3 percentage of participants Interval 0.1 to 17.2

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: Safety Int run-in; only participants who completed the study were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=30 Participants 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.
Time-Averaged GC Dose Changes During the Interventional Phase	341.8 mg Standard Deviation 364.2

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=42 Participants 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.
DAS28-CRP During the Interventional Phase V3 (n=42)	2.2 units on a scale Standard Deviation 0.7
DAS28-CRP During the Interventional Phase CV (n=27)	2.3 units on a scale Standard Deviation 0.8
DAS28-CRP During the Interventional Phase Change from V3 to CV (n=27)	0.2 units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: Visit 3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: Safety Obs Population; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=41 Participants 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.
HAQ-DI During the Interventional Phase V3 (n=41)	1.0 units on a scale Standard Deviation 0.7
HAQ-DI During the Interventional Phase CV (n=28)	0.8 units on a scale Standard Deviation 0.7
HAQ-DI During the Interventional Phase Change from V3 to CV (n=26)	0.0 units on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=40 Participants 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.
VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase V3 (n=40)	16.6 mm Standard Deviation 12.5
VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase CV (n=28)	16.7 mm Standard Deviation 15.9
VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase Change from V3 to CV (n=26)	3.1 mm Standard Deviation 15.4

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=43 Participants 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.
VAS for Pain (VAS-Pain) During the Interventional Phase V3 (n=43)	19.9 mm Standard Deviation 16.5
VAS for Pain (VAS-Pain) During the Interventional Phase CV (n=28)	24.9 mm Standard Deviation 19.0
VAS for Pain (VAS-Pain) During the Interventional Phase Change from V3 to CV (n=28)	6.9 mm Standard Deviation 22.4

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=43 Participants 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.
SJC and TJC During the Interventional Phase SJC V3 (n=43)	0.9 joints Standard Deviation 1.3
SJC and TJC During the Interventional Phase SJC CV (n=29)	0.4 joints Standard Deviation 0.9
SJC and TJC During the Interventional Phase SJC Change from V3 to CV (n=29)	-0.3 joints Standard Deviation 0.8
SJC and TJC During the Interventional Phase TJC V3 (n=43)	0.9 joints Standard Deviation 1.2
SJC and TJC During the Interventional Phase TJC CV (n=29)	1.8 joints Standard Deviation 2.7
SJC and TJC During the Interventional Phase TJC Change from V3 to CV (n=29)	1.0 joints Standard Deviation 2.6

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=37 Participants 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.
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase V3 (n=37)	37.5 units on a scale Standard Deviation 9.9
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase CV (n=26)	35.6 units on a scale Standard Deviation 10.8
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase Change from V3 to CV (n=22)	8.8 units on a scale Standard Deviation 19.0

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=37 Participants 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.
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase MCS V3 (n=37)	47.0 units on a scale Standard Deviation 9.9
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase MCS CV (n=26)	46.2 units on a scale Standard Deviation 9.0
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase MCS: Change from V3 to CV (n=22)	-4.4 units on a scale Standard Deviation 10.6
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase PCS V3 (n=36)	42.5 units on a scale Standard Deviation 7.6
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase PCS CV (n=26)	41.8 units on a scale Standard Deviation 8.8
Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase PCS: Change from V3 to CV (n=22)	-2.1 units on a scale Standard Deviation 6.4

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: ITT Population; n=number of participants analyzed for the given parameter at the specified time point.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=37 Participants 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.
SF-36 Subscale Scores During the Interventional Phase Physical functioning V3 (n=36)	41.52 units on a scale Standard Deviation 10.37
SF-36 Subscale Scores During the Interventional Phase Physical functioning CV (n=26)	41.92 units on a scale Standard Deviation 10.44
SF-36 Subscale Scores During the Interventional Phase Change in physical functioning V3 to CV (n=22)	-1.80 units on a scale Standard Deviation 6.77
SF-36 Subscale Scores During the Interventional Phase Physical sub-score V3 (n=37)	40.61 units on a scale Standard Deviation 7.53
SF-36 Subscale Scores During the Interventional Phase Physical sub-score CV (n=26)	39.85 units on a scale Standard Deviation 8.23
SF-36 Subscale Scores During the Interventional Phase Change in physical sub-score V3 to CV (n=22)	-2.79 units on a scale Standard Deviation 7.68
SF-36 Subscale Scores During the Interventional Phase Bodily pain V3 (n=37)	45.88 units on a scale Standard Deviation 8.35
SF-36 Subscale Scores During the Interventional Phase Bodily pain CV (n=26)	44.65 units on a scale Standard Deviation 9.70
SF-36 Subscale Scores During the Interventional Phase Change in bodily pain V3 to CV (n=22)	-3.21 units on a scale Standard Deviation 8.67
SF-36 Subscale Scores During the Interventional Phase General health V3 (n=37)	43.11 units on a scale Standard Deviation 9.42
SF-36 Subscale Scores During the Interventional Phase General health CV (n=26)	40.82 units on a scale Standard Deviation 8.77
SF-36 Subscale Scores During the Interventional Phase Change in general health V3 to CV (n=22)	-3.78 units on a scale Standard Deviation 7.35
SF-36 Subscale Scores During the Interventional Phase Vitality V3 (n=37)	50.51 units on a scale Standard Deviation 8.74
SF-36 Subscale Scores During the Interventional Phase Vitality CV (n=26)	48.91 units on a scale Standard Deviation 9.13
SF-36 Subscale Scores During the Interventional Phase Change in vitality V3 to CV (n=22)	-4.37 units on a scale Standard Deviation 9.98
SF-36 Subscale Scores During the Interventional Phase Social functioning V3 (n=37)	45.42 units on a scale Standard Deviation 9.63
SF-36 Subscale Scores During the Interventional Phase Social functioning CV (n=26)	45.58 units on a scale Standard Deviation 9.29
SF-36 Subscale Scores During the Interventional Phase Change in social functioning V3 to CV (n=22)	-2.73 units on a scale Standard Deviation 9.63
SF-36 Subscale Scores During the Interventional Phase Emotional sub-score V3 (n=37)	40.59 units on a scale Standard Deviation 9.98
SF-36 Subscale Scores During the Interventional Phase Emotional sub-score CV (n=26)	40.37 units on a scale Standard Deviation 10.53
SF-36 Subscale Scores During the Interventional Phase Change in emotional sub-score V3 to CV (n=22)	-2.45 units on a scale Standard Deviation 10.29
SF-36 Subscale Scores During the Interventional Phase Mental health V3 (n=37)	47.14 units on a scale Standard Deviation 10.00
SF-36 Subscale Scores During the Interventional Phase Mental health CV (n=26)	45.94 units on a scale Standard Deviation 10.37
SF-36 Subscale Scores During the Interventional Phase Change in Mental health V3 to CV (n=22)	-5.47 units on a scale Standard Deviation 10.98

SECONDARY outcome

Timeframe: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3)

Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=40 Participants 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.
CDAI Score During the Interventional Phase V3 (n=40)	5.6 units on a scale Standard Deviation 3.8
CDAI Score During the Interventional Phase CV (n=27)	6.5 units on a scale Standard Deviation 5.4
CDAI Score During the Interventional Phase Change from V3 to CV (n=25)	1.4 units on a scale Standard Deviation 5.2

SECONDARY outcome

Timeframe: 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)

Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.

Outcome measures

Outcome measures
Measure	Tocilizumab n=41 Participants 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.
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V3 LDA (n=40)	85.0 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V3 Remission (n=40)	27.5 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V4 LDA (n=41)	82.9 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V4 Remission (n=41)	39.0 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V5 LDA (n=38)	81.6 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V5 Remission (n=38)	47.4 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V6 LDA (n=35)	71.4 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V6 Remission (n=35)	37.1 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V7 LDA (n=33)	75.8 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V7 Remission (n=33)	33.3 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V8 LDA (n=31)	80.6 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V8 Remission (n=31)	38.7 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V9 LDA (n=29)	69.0 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI V9 Remission (n=29)	31.0 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI CV LDA (n=27)	77.8 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI CV Remission (n=27)	33.3 percentage of participants

SECONDARY outcome

Timeframe: 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)

Population: Safety Int run-in; n=number of participants analyzed for the given parameter at the specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Tocilizumab n=42 Participants 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.
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V3 LDA (n=42)	90.5 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V3 Remission (n=42)	73.8 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V4 LDA (n=41)	85.4 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V4 Remission (n=41)	73.2 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V5 LDA (n=35)	88.6 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V5 Remission (n=35)	71.4 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V6 LDA (n=35)	82.9 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V6 Remission (n=35)	62.9 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V7 LDA (n=33)	90.9 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V7 Remission (n=33)	57.6 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V8 LDA (n=32)	87.5 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V8 Remission (n=32)	62.5 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V9 LDA (n=30)	73.3 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP V9 Remission (n=30)	56.7 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP CV LDA (n=27)	88.9 percentage of participants
Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP CV Remission (n=27)	59.3 percentage of participants

Adverse Events

Noninterventional Phase

Serious events: 4 serious events

Other events: 36 other events

Deaths: 0 deaths

Interventional Phase

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Noninterventional Phase n=68 participants at risk 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.	Interventional Phase n=43 participants at risk 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.
Cardiac disorders Atrial fibrillation	1.5% 1/68 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV	0.00% 0/43 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV
Infections and infestations Cellulitis	1.5% 1/68 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV	0.00% 0/43 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV
Psychiatric disorders Attempted to commit suicide	1.5% 1/68 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV	0.00% 0/43 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV
Musculoskeletal and connective tissue disorders Neck pain	1.5% 1/68 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV	0.00% 0/43 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/68 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV	2.3% 1/43 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV
Infections and infestations Osteitis	1.5% 1/68 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV	0.00% 0/43 • Adverse events were recorded throughout the study from V1, 6 months before Interventional phase to CV

Other adverse events

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 1-800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER