A Study of RoActemra/Actemra (Tocilizumab) Versus Adalimumab in Combination With Methotrexate (MTX) in Patients With Moderate to Severe Active Rheumatoid Arthritis And an Inadequate Response to Treatment With Only One Tumor Necrosis Factor (TNF)-Inhibitor

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. DAS28 Remission is defined as a DAS28 score \<2.6.

Time frame: Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. A higher value indicated higher disease activity. A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other DAS28 components were used as observed.

Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory. ESR was measured in millimeter/hour (mm/hr). A reduction in the level is considered an improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

Blood was collected at Baseline and Week 24. The samples were sent to a central laboratory for Hemoglobin analysis reported in gram/deciliter (g/dL). A positive number change from Baseline (a higher hemoglobin level compared to Baseline) indicated improvement

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with hemoglobin data available at Baseline and Week 24.

Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory. The concentration of CRP was measured in milligram/liter (mg/L). A reduction in the level is considered an improvement

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

RAPID3 is a patient self reported assessment that combines the HAQ-DI \[20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions answered on a 4-point scale where 0=without any difficulty to 3=unable to do} converted to a score of 0-10, the Patients Assessment of Pain \[Over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain\] converted to a score of 0-10 and the Patient's Global Assessment of Disease Activity \[over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity\] converted to a score of 0-10. The 3 individual scales are summed for a raw score of 0-30 which is divided by 3 to achieve a total possible adjusted score of 0-10. A negative change from Baseline indicates improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24 for this outcome measure.

66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 24

Population: Intent-to-treat population included all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment. Last observation was used to impute missing swollen joint counts.

68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 24

Population: Intent-to-treat population included all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment. Last observation carried forward was used to impute missing tender joint counts.

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient'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 patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status. A positive change from Baseline indicates improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

The patient's global assessment of disease activity is assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24.

An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Time frame: 32 weeks

Population: Safety Population included all participants who received study drug and who had at least 1 post-dose safety assessment.

ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with ACR score data available. Last observation carried forward was used to impute missing tender and swollen joint counts. All other ACR components were used as observed.

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. LDAS is defined as DAS28 ≤3.2.

Time frame: Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Baseline and Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other DAS28 components were used as observed.

The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total score ranges from 0 (best) to 10 (worst). A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 or a change from Baseline \< -1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a change from Baseline \< -0.6 to ≥ -1.2.

Time frame: Baseline, Week 24

Population: Participants from the Intent-to-treat population, all randomized participants who received study drug and had at least 1 post-baseline efficacy assessment, with data available at Week 24. Last observation carried forward was used to impute missing tender and swollen joint counts. All other EULAR components were used as observed.