TORPEDO Study: A Study on Rapid Effect of Tocilizumab in Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) or Anti-TNF

Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period

Participants were asked to rate their assessment of disease activity using a visual analog scale (VAS) of 0 to 100 millimeters (mm), where 0 represented no symptoms and 100 represented severe symptoms. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

Time frame: Baseline, Weeks 1 and 4

Patient Global Assessment of Disease Activity During the Open Treatment Period

Participants were asked to rate their assessment of disease activity using a VAS of 0 to 100 mm, where 0 represented no symptoms and 100 represented severe symptoms. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

Time frame: Baseline, Weeks 12, 24, 36 and 48

Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period

Physicians were asked to assess disease activity of the participants using a VAS of 0 to 100 mm, where 0 represented no symptoms and 100 represented severe symptoms. Physicians were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

Time frame: Baseline and Week 4

Physician Global Assessment of Disease Activity During the Open Treatment Period

Physicians were asked to assess disease activity of the participants using a VAS of 0 to 100 mm, where 0 represented no symptoms and 100 represented severe symptoms. Physicians were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Patient Global Assessment of Pain During the Double-Blind Treatment Period

Participants were asked to rate their assessment of pain using a VAS of 0 to 100 mm, where 0 represented no pain and 100 represented intolerable pain. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

Time frame: Baseline and Week 4

Patient Global Assessment of Pain During the Open Treatment Period

Participants were asked to rate their assessment of pain using a VAS of 0 to 100 mm, where 0 represented no pain and 100 represented intolerable pain. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

Time frame: Baseline and Weeks 12, 24, 36, and 48

Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound

Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 metacarpal phalangeal \[MCP; left and right\] joints, 5 proximal interphalangeal \[PIP; left and right\] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 metatarsal phalangeal \[MTP; left and right\] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120. A score of 0 indicated no damage and a score of 120 indicated most severe damage. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. A negative change from baseline indicated improvement.

Time frame: Baseline, Weeks 1 and 4

Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound

Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 MCP \[left and right\] joints, 5 PIP \[left and right\] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120 (higher score=more severe disease). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. Negative change from baseline indicated improvement.

Time frame: Baseline, Weeks 1 and 4

Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound

Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 MCP \[left and right\] joints, 5 PIP \[left and right\] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120 (higher score=more severe disease). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. Relative change was the percentage (%) change from baseline.

Time frame: Weeks 12, 24, and 48

Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound

Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 MCP \[left and right\] joints, 5 PIP \[left and right\] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120 (higher score=more severe disease). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. Relative change was the percentage change from baseline.

Time frame: Weeks 12, 24, and 48

Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period

Erythrocyte sedimentation rate is a biological marker of inflammation, measured in mm per hour (mm/hr). A reduction in ESR indicates improvement.

Time frame: Baseline, Weeks 1 and 4

Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment

Erythrocyte sedimentation rate is a biological marker of inflammation. A negative change indicates improvement.

Time frame: Weeks 1 and 4

Erythrocyte Sedimentation Rate During the Open Treatment Period

Erythrocyte sedimentation rate is a biological marker of inflammation, measured in mm/hr. A reduction in ESR indicates improvement. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

Time frame: Baseline, Weeks 12, 24, 36, and 48

C-Reactive Protein During the Double-Blind Treatment Period

C-Reactive protein (CRP) is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL). A reduction in CRP indicates improvement.

Time frame: Baseline, Weeks 1 and 4

Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period

C-Reactive protein (CRP) is a biological marker of inflammation. Negative changes from baseline indicate improvement.

Time frame: Weeks 1 and 4

C- Reactive Protein During the Open Treatment Period

C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Serum Amyloid A Component During the Double-Blind Treatment Period

Serum Amyloid A (SAA) component is a biological marker of inflammation and is measured in mg/L. A reduction in SAA indicates improvement.

Time frame: Baseline, Weeks 1 and 4

Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period

Serum Amyloid A (SAA) component is a biological marker of inflammation. A negative change from baseline indicates improvement.

Time frame: Weeks 1 and 4

Serum Amyloid A Component During the Open Treatment Period

Serum Amyloid A (SAA) component is a biological marker of inflammation measured in mg/L. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Beta 2 Microglobulin Levels During the Open Treatment Period

Beta 2 Microglobulin is a biological marker of inflammation measured in micrograms per milliliter (mcg/mL). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Beta 2 Microglobulin Levels During the Double-Blind Treatment Period

Beta 2 Microglobulin is a biological marker of inflammation measured in micrograms per milliliter (mcg/mL).

Time frame: Baseline, Weeks 1 and 4

Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period

Beta 2 Microglobulin is a biological marker of inflammation. If baseline value was equal to 0, it was replaced by 0.1 to calculate the change from baseline.

Time frame: Weeks 1 and 4

Bone Mineral Density

To describe bone mineral density (BMD), standardized values were calculated for lumbar spine, hip, femoral neck, and trochanter, taking into account the type of Dual energy X ray absorptiometry (DXA) used. All DXA at baseline were taken into account (done from before screening to Week 8). DXA at end of study were taken into account if they were done after at least 6 infusions of tocilizumab. Values were measured in milligrams per square centimeter (mg/cm\^2).

Time frame: Baseline and Week 48

Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period

Time frame: Baseline, Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period

S-Sclerostin and P-Dkk1 are biological markers of bone and cartilage metabolism measured as picograms/milliliter (pg/mL). Baseline is the closest value plus or minus (+/-) 1 month around the first tocilizumab infusion. If values before and after the first infusion were eligible, the value before was taken into account.

Time frame: Baseline, Weeks 12, 24, and 48

Serum Procollagen Type II N-Propeptide (s-PIINP), Serum Procollagen Type I N Propeptide (s-PINP), and Serum Carboxy-Terminal Collagen Crosslinks-1 (s-CTX-I) Over the 1-Year Tocilizumab Period

S-PIIINP, S-CTX-I, and S-PINP are biological markers of bone and cartilage metabolism. Baseline is the closest value +/- 1 month around the first tocilizumab infusion. If values before and after the first infusion were eligible, the value before was taken into account.

Time frame: Baseline and Weeks 12, 24, and 48

Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period

S-OGP is a biological marker of bone and cartilage metabolism measured as picomoles per liter (pmol/L). Baseline is the closest value +/- 1 month around the first tocilizumab infusion. If values before and after the first infusion were eligible, the value before was taken into account.

Time frame: Baseline and Weeks 12 and 48

Weekly Methotrexate (MTX) Dose

Before entering the study, participants had to be treated with MTX for at least 12 weeks and at a stable dose for at least 8 weeks before the screening visit (10-25 mg per week \[mg/week\] of oral or parenteral MTX). During the study, treatment with MTX had to be stable during the first month and then could be continued or modified, at the investigator's discretion.

Time frame: Baseline and Weeks 24 and 48

HAQ-DI During the Double-Blind Treatment Period

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Screening and Week 4

HAQ-DI During the Open Treatment Period

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline and Weeks 12, 24, 36, and 48

Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period

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 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 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). A higher score reflects an improvement in the participant's health status. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

Time frame: Day 0, Week 1, and Week 4

Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period

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 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 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). A higher score reflects an improvement in the participant's health status. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

Time frame: Week 1 and Week 4

FACIT-F During the Open Treatment Period

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 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 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). A higher score reflects an improvement in the participant's health status. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Hemoglobin Concentration During the Double-Blind Treatment Period

Hemoglobin concentrations were determined at each visit to evaluate anemia in participants and measured as grams per deciliter (g/dL).

Time frame: Baseline and Weeks 1 and 4

Hemoglobin Concentration During the Open Treatment Period

Hemoglobin concentrations were determined at each visit to evaluate anemia in participants and measured as g/dL.

Time frame: Baseline, Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period

Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28. Baseline = value at Day 0 if available, value at screening otherwise.

Time frame: Baseline and Weeks 1 and 4

Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period

Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28.

Time frame: Weeks 1 and 4

TJC Based on 28-Joint Count During the Open Treatment Period

Twenty-eight joints were assessed for tenderness and joints were classified as tender (1)/not tender (0), giving a total possible tender joint count score of 0 to 28. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

Time frame: Baseline and Weeks 12, 24, 36, and 48

TJC Based on 40-Joint Count During the Double-Blind Treatment Period

Forty joints were assessed for tenderness (5 MCP \[left and right\] joints, 5 PIP \[left and right joints\], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints). Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 40. Baseline = value at Day 0 if available, value at screening otherwise.

Time frame: Baseline and Weeks 1 and 4

Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period

Forty joints were assessed for tenderness (5 MCP \[left and right\] joints, 5 PIP \[left and right joints\], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints). Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 40.

Time frame: Weeks 1 and 4

TJC Based on 40-Joint Count During the Open Treatment Period

Forty joints were assessed for tenderness (5 MCP \[left and right\] joints, 5 PIP \[left and right joints\], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints). Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 40. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

Time frame: Baseline and Weeks 12, 24, 36, and 48

Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period

Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 28. Baseline = value at Day 0 if available, value at screening otherwise.

Time frame: Baseline and Weeks 1 and 4

Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period

Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 28.

Time frame: Weeks 1 and 4

Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period

Twenty-eight joints were assessed for swelling (5 MCP \[left and right\] joints, 5 PIP \[left and right joints\], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints) . Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 28. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

Time frame: Baseline and Weeks 12, 24, 36, and 48

SJC Based on 40-Joint Count During the Double-Blind Treatment Period

Forty joints were assessed for swelling (5 MCP \[left and right\] joints, 5 PIP \[left and right joints\], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints). Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 40. Baseline = value at Day 0 if available, value at screening otherwise.

Time frame: Baseline and Weeks 1 and 4

Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period

Forty joints were assessed for swelling (5 MCP \[left and right\] joints, 5 PIP \[left and right joints\], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints). Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 40.

Time frame: Weeks 1 and 4

SJC Based on 40-Joint Count During the Open Treatment Period

Forty joints were assessed for swelling (5 MCP \[left and right\] joints, 5 PIP \[left and right joints\], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP \[left and right\] joints). Joints were classified as swollen (1)/not swollen (0) for a total possible score of 0 to 40. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

Time frame: Baseline and Weeks 12, 24, 36, and 48

Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period

DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.

Time frame: Baseline and Weeks 1 and 4

DAS28 During the Open Treatment Period

DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.

Time frame: Baseline and Weeks 12, 24, 36, and 48

Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period

DAS40 calculated from the number of swollen joints and tender joints using the 40-joint count, the erythrocyte sedimentation rate and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.

Time frame: Baseline and Weeks 1 and 4

DAS40 During the Open Treatment Period

DAS40 was calculated from the number of swollen joints and tender joints using the 40-joint count, the erythrocyte sedimentation rate, and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS40 score ranged from 0 to 10, where higher scores correspond to greater disease activity.

Time frame: Baseline and Weeks 12, 24, 36, and 48