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

Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase

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)

Percentage of Participants Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase

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)

Percentage of Participants With Erosions During the NonInterventional Phase

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)

Number of Erosions During the NonInterventional Phase

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)

Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase

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)

Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase

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)

Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase

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)

DAS28-CRP During the Noninterventional Phase

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)

DAS28-ESR During the Noninterventional Phase

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)

Clinical Disease Activity Index (CDAI) During the Noninterventional Phase

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)

Median Time Interval Between V1 and V2

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)

Median Dose of Tocilizumab During the Noninterventional Phase

Time frame: V1 and V2 (up to 6 months after V1)

Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase

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)

Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase

Time frame: V1 and V2 (up to 6 months after V1)

Percentage of Participants Able to Start the GC Reduction Phase at V3

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)

Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9

Time frame: V9 (24 weeks after V3)

Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9

Time frame: V9 (24 weeks after V3)

Time-Averaged GC Dose Changes During the Interventional Phase

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)

DAS28-CRP During the Interventional Phase

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)

HAQ-DI During the Interventional Phase

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)

VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase

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)

VAS for Pain (VAS-Pain) During the Interventional Phase

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)

SJC and TJC During the Interventional Phase

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)

Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase

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)

Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase

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)

SF-36 Subscale Scores During the Interventional Phase

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)

CDAI Score During the Interventional Phase

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)

Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI

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)

Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP

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)