Rheumatoid Arthritis
Conditions
Brief summary
This study will assess the onset and maintenance of effect of tocilizumab on relief in patients with active moderate or severe rheumatoid arthritis who have had an inadequate response to DMARDs or anti-TNF. For the first, double-blind, part of the study patients will be randomized to receive an iv infusion of either 8mg/kg tocilizumab or placebo. After 4 weeks this will be followed by 11 months treatment with tocilizumab 8mg/kg iv infusion every 4 weeks. Methotrexate or DMARD therapy will be continued throughout study treatment. Target sample size is \>100.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
single iv infusion 8 mg/kg
DRUGplacebo
single iv infusion
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients \>/= 18 years of age * active moderate or severe rheumatoid arthritis of \<10 years duration with inadequate response to methotrexate or anti-TNF * on methotrexate treatment for at least 10 weeks, at least 8 weeks on stable dose * patients receiving oral corticosteroids and/or NSAIDs should be at stable dose for 4 weeks
Exclusion criteria
* rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA * functional class IV by ACR classification * history of inflammatory joint disease other than RA * previous treatment with cell-depleting therapies, abatacept or rituximab * active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with iv antibiotics \<4 weeks or oral antibiotics \<2 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4 | Week 4 | HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Relevant clinical improvement was defined as a reduction of at least 0.22 points in HAQ-DI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Assessment of Disease Activity During the Open Treatment Period | Baseline, Weeks 12, 24, 36 and 48 | 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. |
| Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period | Baseline and Week 4 | 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. |
| Physician Global Assessment of Disease Activity During the Open Treatment Period | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Patient Global Assessment of Pain During the Double-Blind Treatment Period | Baseline and Week 4 | 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. |
| Patient Global Assessment of Pain During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Baseline, Weeks 1 and 4 | 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. |
| Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Baseline, Weeks 1 and 4 | 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. |
| Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound | Weeks 12, 24, and 48 | 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. |
| Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound | Weeks 12, 24, and 48 | 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. |
| Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period | Baseline, Weeks 1 and 4 | Erythrocyte sedimentation rate is a biological marker of inflammation, measured in mm per hour (mm/hr). A reduction in ESR indicates improvement. |
| Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment | Weeks 1 and 4 | Erythrocyte sedimentation rate is a biological marker of inflammation. A negative change indicates improvement. |
| Erythrocyte Sedimentation Rate During the Open Treatment Period | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| C-Reactive Protein During the Double-Blind Treatment Period | Baseline, Weeks 1 and 4 | 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. |
| Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period | Weeks 1 and 4 | C-Reactive protein (CRP) is a biological marker of inflammation. Negative changes from baseline indicate improvement. |
| C- Reactive Protein During the Open Treatment Period | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Serum Amyloid A Component During the Double-Blind Treatment Period | Baseline, Weeks 1 and 4 | Serum Amyloid A (SAA) component is a biological marker of inflammation and is measured in mg/L. A reduction in SAA indicates improvement. |
| Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period | Weeks 1 and 4 | Serum Amyloid A (SAA) component is a biological marker of inflammation. A negative change from baseline indicates improvement. |
| Serum Amyloid A Component During the Open Treatment Period | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Beta 2 Microglobulin Levels During the Open Treatment Period | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Baseline, Weeks 1 and 4 | Beta 2 Microglobulin is a biological marker of inflammation measured in micrograms per milliliter (mcg/mL). |
| Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Weeks 1 and 4 | 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. |
| Bone Mineral Density | Baseline and Week 48 | 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). |
| Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | 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 | Baseline, Weeks 12, 24, and 48 | 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. |
| 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 | Baseline and Weeks 12, 24, and 48 | 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. |
| Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period | Baseline and Weeks 12 and 48 | 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. |
| Weekly Methotrexate (MTX) Dose | Baseline and Weeks 24 and 48 | 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. |
| HAQ-DI During the Double-Blind Treatment Period | Screening and Week 4 | 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. |
| HAQ-DI During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period | Day 0, Week 1, and Week 4 | 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. |
| Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period | Week 1 and Week 4 | 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. |
| FACIT-F During the Open Treatment Period | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Hemoglobin Concentration During the Double-Blind Treatment Period | Baseline and Weeks 1 and 4 | Hemoglobin concentrations were determined at each visit to evaluate anemia in participants and measured as grams per deciliter (g/dL). |
| Hemoglobin Concentration During the Open Treatment Period | Baseline, Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 | Hemoglobin concentrations were determined at each visit to evaluate anemia in participants and measured as g/dL. |
| Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Baseline and Weeks 1 and 4 | 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. |
| Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period | Weeks 1 and 4 | 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. |
| TJC Based on 28-Joint Count During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Baseline and Weeks 1 and 4 | 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. |
| Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Weeks 1 and 4 | 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. |
| TJC Based on 40-Joint Count During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Baseline and Weeks 1 and 4 | 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. |
| Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period | Weeks 1 and 4 | 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. |
| Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Baseline and Weeks 1 and 4 | 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. |
| Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Baseline, Weeks 1 and 4 | 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. |
| SJC Based on 40-Joint Count During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Baseline and Weeks 1 and 4 | 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. |
| DAS28 During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Baseline and Weeks 1 and 4 | 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. |
| DAS40 During the Open Treatment Period | Baseline and Weeks 12, 24, 36, and 48 | 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. |
| Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Weeks 1 and 4 | 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. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Tocilizumab Participants received placebo solution (containing polysorbate 80, sucrose, and water for injection) IV during the Double-Blind Treatment Period on Day 0. Starting at Week 4, participants received tocilizumab 8 mg/kg (800 mg maximum) IV, once every 4 weeks up to 11 months (up to Week 44), for a maximum of 11 infusions. | 50 |
| Tocilizumab Participants received tocilizumab IV once every 4 weeks up to 12 months (up to Week 44), for a maximum of 12 infusions. | 53 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo, Tocilizumab | Tocilizumab | Total |
|---|---|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 11.8 | 52.8 years STANDARD_DEVIATION 11.6 | 52.0 years STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 36 Participants | 41 Participants | 77 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 53 | 15 / 50 |
| serious Total, serious adverse events | 13 / 53 | 11 / 50 |
Outcome results
Primary
Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4
HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Relevant clinical improvement was defined as a reduction of at least 0.22 points in HAQ-DI.
Time frame: Week 4
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, Tocilizumab | Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4 | 42.0 percentage of participants |
| Tocilizumab | Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4 | 49.1 percentage of participants |
p-value: 0.472Chi-squared
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Baseline (n=39,49) | 2.0 mg/L | Standard Deviation 0.6 |
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 1 (n=45,48) | 2.0 mg/L | Standard Deviation 0.5 |
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 4 (n=45,47) | 2.0 mg/L | Standard Deviation 0.5 |
| Tocilizumab | Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Baseline (n=39,49) | 2.0 mg/L | Standard Deviation 0.6 |
| Tocilizumab | Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 1 (n=45,48) | 2.1 mg/L | Standard Deviation 0.7 |
| Tocilizumab | Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 4 (n=45,47) | 2.0 mg/L | Standard Deviation 0.5 |
Secondary
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
Population: One-Year Efficacy Population;n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Open Treatment Period | Baseline (n=96) | 2.0 mcg/mL | Standard Deviation 0.6 |
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Open Treatment Period | Week 24 (n=78) | 1.9 mcg/mL | Standard Deviation 0.6 |
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Open Treatment Period | Week 36 (n=69) | 2.0 mcg/mL | Standard Deviation 0.5 |
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Open Treatment Period | Week 48 (n=64) | 1.9 mcg/mL | Standard Deviation 0.5 |
| Placebo, Tocilizumab | Beta 2 Microglobulin Levels During the Open Treatment Period | Week 12 (n=87) | 2.0 mcg/mL | Standard Deviation 0.6 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Bone Mineral Density | Lumbar spine, Baseline (n=89) | 1018.0 mg/cm^2 | Standard Deviation 155.4 |
| Placebo, Tocilizumab | Bone Mineral Density | Lumbar spine, Week 48 (n=82) | 1033.4 mg/cm^2 | Standard Deviation 157.9 |
| Placebo, Tocilizumab | Bone Mineral Density | Hip, Baseline (n=90) | 887.3 mg/cm^2 | Standard Deviation 129.8 |
| Placebo, Tocilizumab | Bone Mineral Density | Hip, Week 48 (n=83) | 891.3 mg/cm^2 | Standard Deviation 131.6 |
| Placebo, Tocilizumab | Bone Mineral Density | Femoral neck, Baseline (n=90) | 825.0 mg/cm^2 | Standard Deviation 122.7 |
| Placebo, Tocilizumab | Bone Mineral Density | Femoral neck, Week 48 (n=83) | 821.8 mg/cm^2 | Standard Deviation 121.6 |
| Placebo, Tocilizumab | Bone Mineral Density | Trochanter, Baseline (n=90) | 696.2 mg/cm^2 | Standard Deviation 124.3 |
| Placebo, Tocilizumab | Bone Mineral Density | Trochanter, Week 48 (n=83) | 700.3 mg/cm^2 | Standard Deviation 122.7 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | C-Reactive Protein During the Double-Blind Treatment Period | Baseline (n=47,53) | 18.6 ng/mL | Standard Deviation 23.6 |
| Placebo, Tocilizumab | C-Reactive Protein During the Double-Blind Treatment Period | Week 1 (n=47,52) | 20.4 ng/mL | Standard Deviation 34.3 |
| Placebo, Tocilizumab | C-Reactive Protein During the Double-Blind Treatment Period | Week 4 (n=48,52) | 17.5 ng/mL | Standard Deviation 21.8 |
| Tocilizumab | C-Reactive Protein During the Double-Blind Treatment Period | Baseline (n=47,53) | 14.2 ng/mL | Standard Deviation 21.8 |
| Tocilizumab | C-Reactive Protein During the Double-Blind Treatment Period | Week 1 (n=47,52) | 2.3 ng/mL | Standard Deviation 2 |
| Tocilizumab | C-Reactive Protein During the Double-Blind Treatment Period | Week 4 (n=48,52) | 3.8 ng/mL | Standard Deviation 9.4 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | C- Reactive Protein During the Open Treatment Period | Baseline (n=102) | 15.8 ng/L | Standard Deviation 20.8 |
| Placebo, Tocilizumab | C- Reactive Protein During the Open Treatment Period | Week 24 (n=92) | 3.2 ng/L | Standard Deviation 5.2 |
| Placebo, Tocilizumab | C- Reactive Protein During the Open Treatment Period | Week 36 (n=80) | 3.9 ng/L | Standard Deviation 6.6 |
| Placebo, Tocilizumab | C- Reactive Protein During the Open Treatment Period | Week 48 (n=81) | 2.6 ng/L | Standard Deviation 2.6 |
| Placebo, Tocilizumab | C- Reactive Protein During the Open Treatment Period | Week 12 (n=95) | 3.9 ng/L | Standard Deviation 9.7 |
Secondary
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
Population: One-Year Efficacy Population n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | DAS28 During the Open Treatment Period | Baseline (n=102) | 5.51 units on a scale | Standard Deviation 1.04 |
| Placebo, Tocilizumab | DAS28 During the Open Treatment Period | Week 12 (n=95) | 2.98 units on a scale | Standard Deviation 1.4 |
| Placebo, Tocilizumab | DAS28 During the Open Treatment Period | Week 24 (n=89) | 2.64 units on a scale | Standard Deviation 1.31 |
| Placebo, Tocilizumab | DAS28 During the Open Treatment Period | Week 36 (n=83) | 2.51 units on a scale | Standard Deviation 1.36 |
| Placebo, Tocilizumab | DAS28 During the Open Treatment Period | Week 48 (n=79) | 2.22 units on a scale | Standard Deviation 1.28 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | DAS40 During the Open Treatment Period | Baseline (n=102) | 5.96 units on a scale | Standard Deviation 1.06 |
| Placebo, Tocilizumab | DAS40 During the Open Treatment Period | Week 12 (n=95) | 3.27 units on a scale | Standard Deviation 1.49 |
| Placebo, Tocilizumab | DAS40 During the Open Treatment Period | Week 24 (n=89) | 2.89 units on a scale | Standard Deviation 1.4 |
| Placebo, Tocilizumab | DAS40 During the Open Treatment Period | Week 36 (n=83) | 2.76 units on a scale | Standard Deviation 1.42 |
| Placebo, Tocilizumab | DAS40 During the Open Treatment Period | Week 48 (n=79) | 2.48 units on a scale | Standard Deviation 1.4 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Week 1 (n=41,40) | 5.40 units on a scale | Standard Deviation 1.04 |
| Placebo, Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Week 4 (n=45,50) | 5.27 units on a scale | Standard Deviation 1 |
| Placebo, Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Change at Week 1 (n=41,40) | -0.43 units on a scale | Standard Deviation 0.81 |
| Placebo, Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Change at Week 4 (n=45,50) | -0.43 units on a scale | Standard Deviation 0.9 |
| Placebo, Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Baseline (n=50,53) | 5.66 units on a scale | Standard Deviation 1.02 |
| Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Change at Week 4 (n=45,50) | -1.68 units on a scale | Standard Deviation 0.94 |
| Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Baseline (n=50,53) | 5.64 units on a scale | Standard Deviation 1.04 |
| Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Week 1 (n=41,40) | 4.41 units on a scale | Standard Deviation 1.05 |
| Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Change at Week 1 (n=41,40) | -1.12 units on a scale | Standard Deviation 0.61 |
| Tocilizumab | Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period | Week 4 (n=45,50) | 4.00 units on a scale | Standard Deviation 1.26 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Week 1 (n=41,40) | 5.88 units on a scale | Standard Deviation 1.12 |
| Placebo, Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Week 4 (n=45,50) | 5.70 units on a scale | Standard Deviation 1.03 |
| Placebo, Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Change at Week 1 (n=41,40) | -0.43 units on a scale | Standard Deviation 0.85 |
| Placebo, Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Change at Week 4 (n=45,50) | -0.49 units on a scale | Standard Deviation 1.03 |
| Placebo, Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Baseline (n=50,53) | 6.15 units on a scale | Standard Deviation 1.03 |
| Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Change at Week 4 (n=45,50) | -1.75 units on a scale | Standard Deviation 1.03 |
| Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Baseline (n=50,53) | 6.08 units on a scale | Standard Deviation 1.04 |
| Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Week 1 (n=41,40) | 4.71 units on a scale | Standard Deviation 1.16 |
| Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Change at Week 1 (n=41,40) | -1.25 units on a scale | Standard Deviation 0.64 |
| Tocilizumab | Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period | Week 4 (n=45,50) | 4.39 units on a scale | Standard Deviation 1.37 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period | Baseline (n=50,53) | 27.5 mm/hr | Standard Deviation 22.9 |
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period | Week 1 (n=49,51) | 27.6 mm/hr | Standard Deviation 24.2 |
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period | Week 4 (n=50,51) | 26.6 mm/hr | Standard Deviation 19.9 |
| Tocilizumab | Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period | Baseline (n=50,53) | 28.1 mm/hr | Standard Deviation 25.6 |
| Tocilizumab | Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period | Week 1 (n=49,51) | 11.9 mm/hr | Standard Deviation 12.7 |
| Tocilizumab | Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period | Week 4 (n=50,51) | 8.2 mm/hr | Standard Deviation 11 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Open Treatment Period | Baseline (n=103) | 27.8 mm/hr | Standard Deviation 22.8 |
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Open Treatment Period | Week 12 (n=96) | 6.8 mm/hr | Standard Deviation 11.4 |
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Open Treatment Period | Week 24 (n=92) | 5.9 mm/hr | Standard Deviation 6.1 |
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Open Treatment Period | Week 36 (n=84) | 8.0 mm/hr | Standard Deviation 13.4 |
| Placebo, Tocilizumab | Erythrocyte Sedimentation Rate During the Open Treatment Period | Week 48 (n=80) | 4.6 mm/hr | Standard Deviation 3.5 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | FACIT-F During the Open Treatment Period | Baseline (n=102) | 27.1 units on a scale | Standard Deviation 11.1 |
| Placebo, Tocilizumab | FACIT-F During the Open Treatment Period | Week 12 (n=93) | 33.7 units on a scale | Standard Deviation 11.2 |
| Placebo, Tocilizumab | FACIT-F During the Open Treatment Period | Week 24 (n=90) | 35.4 units on a scale | Standard Deviation 10.4 |
| Placebo, Tocilizumab | FACIT-F During the Open Treatment Period | Week 36 (n=82) | 34.0 units on a scale | Standard Deviation 10.3 |
| Placebo, Tocilizumab | FACIT-F During the Open Treatment Period | Week 48 (n=82) | 34.9 units on a scale | Standard Deviation 10.6 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period | Day 0 (n=50,52) | 23.9 units on a scale | Standard Deviation 10.1 |
| Placebo, Tocilizumab | Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period | Week 1 (n=48,52) | 27.3 units on a scale | Standard Deviation 11.7 |
| Placebo, Tocilizumab | Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period | Week 4 (n=49,52) | 29.2 units on a scale | Standard Deviation 11 |
| Tocilizumab | Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period | Day 0 (n=50,52) | 26.0 units on a scale | Standard Deviation 10.6 |
| Tocilizumab | Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period | Week 1 (n=48,52) | 27.7 units on a scale | Standard Deviation 10.4 |
| Tocilizumab | Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period | Week 4 (n=49,52) | 28.9 units on a scale | Standard Deviation 11 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | HAQ-DI During the Double-Blind Treatment Period | Screening (n=50,53) | 1.62 units on a scale | Standard Deviation 0.56 |
| Placebo, Tocilizumab | HAQ-DI During the Double-Blind Treatment Period | Week 4 (n=50,51) | 1.44 units on a scale | Standard Deviation 0.6 |
| Placebo, Tocilizumab | HAQ-DI During the Double-Blind Treatment Period | Change at Week 4 (n=50,51) | -0.18 units on a scale | Standard Deviation 0.47 |
| Tocilizumab | HAQ-DI During the Double-Blind Treatment Period | Week 4 (n=50,51) | 1.39 units on a scale | Standard Deviation 0.65 |
| Tocilizumab | HAQ-DI During the Double-Blind Treatment Period | Change at Week 4 (n=50,51) | -0.22 units on a scale | Standard Deviation 0.49 |
| Tocilizumab | HAQ-DI During the Double-Blind Treatment Period | Screening (n=50,53) | 1.60 units on a scale | Standard Deviation 0.58 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Baseline (n=47,56) | 1.45 units on a scale | Standard Deviation 0.61 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 12 (n=45,49) | -0.29 units on a scale | Standard Deviation 0.52 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Week 24 (n=39,50) | 1.00 units on a scale | Standard Deviation 0.69 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 24 (n=39,50) | -0.50 units on a scale | Standard Deviation 0.54 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Week 36 (n=39,45) | 1.05 units on a scale | Standard Deviation 0.76 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 36 (n=39,45) | -0.44 units on a scale | Standard Deviation 0.75 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Week 48 (n=37,45) | 0.98 units on a scale | Standard Deviation 0.78 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 48 (n=37,45) | -0.47 units on a scale | Standard Deviation 0.71 |
| Placebo, Tocilizumab | HAQ-DI During the Open Treatment Period | Week 12 (n=45,49) | 1.19 units on a scale | Standard Deviation 0.68 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 48 (n=37,45) | -0.72 units on a scale | Standard Deviation 0.6 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Baseline (n=47,56) | 1.62 units on a scale | Standard Deviation 0.57 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Week 12 (n=45,49) | 1.06 units on a scale | Standard Deviation 0.7 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 36 (n=39,45) | -0.64 units on a scale | Standard Deviation 0.64 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 12 (n=45,49) | -0.62 units on a scale | Standard Deviation 0.62 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Change at Week 24 (n=39,50) | -0.68 units on a scale | Standard Deviation 0.61 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Week 48 (n=37,45) | 0.95 units on a scale | Standard Deviation 0.63 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Week 24 (n=39,50) | 1.01 units on a scale | Standard Deviation 0.71 |
| Tocilizumab | HAQ-DI During the Open Treatment Period | Week 36 (n=39,45) | 1.02 units on a scale | Standard Deviation 0.71 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Week 1 (n=50,51) | 12.96 g/dL | Standard Deviation 1.33 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Change at Week 4 (n=50,53) | -0.09 g/dL | Standard Deviation 0.54 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Week 4 (n=50,53) | 12.88 g/dL | Standard Deviation 1.46 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Change at Week 1 (n=50,51) | -0.01 g/dL | Standard Deviation 0.54 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Baseline (n=50,53) | 12.97 g/dL | Standard Deviation 1.37 |
| Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Change at Week 1 (n=50,51) | 0.34 g/dL | Standard Deviation 0.54 |
| Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Baseline (n=50,53) | 12.74 g/dL | Standard Deviation 1.49 |
| Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Week 1 (n=50,51) | 13.04 g/dL | Standard Deviation 1.38 |
| Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Week 4 (n=50,53) | 13.10 g/dL | Standard Deviation 1.41 |
| Tocilizumab | Hemoglobin Concentration During the Double-Blind Treatment Period | Change at Week 4 (n=50,53) | 0.36 g/dL | Standard Deviation 0.69 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Baseline (n=103) | 12.80 g/dL | Standard Deviation 1.47 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 8 (n=99) | 13.14 g/dL | Standard Deviation 1.41 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 12 (n=97) | 13.37 g/dL | Standard Deviation 1.4 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 16 (n=95) | 13.24 g/dL | Standard Deviation 1.51 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 20 (n=91) | 13.27 g/dL | Standard Deviation 1.46 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 24 (n=92) | 13.38 g/dL | Standard Deviation 1.43 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 28 (n=91) | 13.47 g/dL | Standard Deviation 1.32 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 32 (n=90) | 13.46 g/dL | Standard Deviation 1.35 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 36 (n=84) | 13.50 g/dL | Standard Deviation 1.31 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 40 (n=81) | 13.49 g/dL | Standard Deviation 1.35 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 44 (n=82) | 13.48 g/dL | Standard Deviation 1.37 |
| Placebo, Tocilizumab | Hemoglobin Concentration During the Open Treatment Period | Week 48 (n=81) | 13.64 g/dL | Standard Deviation 1.32 |
Secondary
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
Population: ITT Population; number (n) = number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Change at Week 1 (n=42,42) | -11.0 mm | Standard Deviation 19.7 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Week 1 (n=42,42) | 49.0 mm | Standard Deviation 23.2 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Week 4 (n=45,51) | 49.2 mm | Standard Deviation 24 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Change at Week 4 (n=45,51) | -14.3 mm | Standard Deviation 23.6 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Baseline (n=50,53) | 58.8 mm | Standard Deviation 21.1 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Change at Week 4 (n=45,51) | -9.6 mm | Standard Deviation 17.4 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Baseline (n=50,53) | 64.3 mm | Standard Deviation 17.4 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Week 4 (n=45,51) | 51.1 mm | Standard Deviation 22.7 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Week 1 (n=42,42) | 54.2 mm | Standard Deviation 20.6 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period | Change at Week 1 (n=42,42) | -7.4 mm | Standard Deviation 17.8 |
Comparison: Change at Week 1p-value: 0.377Student t-test
Comparison: Change at Week 4p-value: 0.276Student t-test
Secondary
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
Population: ITT Population; 3 participants were randomized to the placebo treatment group but received tocilizumab. n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Baseline (n=46,56) | 51.2 mm | Standard Deviation 22.9 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 12 (n=45,51) | 36.0 mm | Standard Deviation 23.8 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 12 (n=44,51) | -16.2 mm | Standard Deviation 27.6 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 24 (n=438,48) | 27.4 mm | Standard Deviation 21.7 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 24 (n=42,48) | -25.3 mm | Standard Deviation 28.5 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 36 (n=38,46) | -24.2 mm | Standard Deviation 27.8 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 48 (n=36,45) | 25.6 mm | Standard Deviation 24.4 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 48 (n=35,45) | -24.9 mm | Standard Deviation 28.5 |
| Placebo, Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 36 (n=39,46) | 25.7 mm | Standard Deviation 18.1 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 24 (n=42,48) | -27.2 mm | Standard Deviation 24.5 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Baseline (n=46,56) | 59.4 mm | Standard Deviation 21.1 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 36 (n=39,46) | 28.7 mm | Standard Deviation 24.5 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 12 (n=45,51) | 32.7 mm | Standard Deviation 24.7 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 48 (n=36,45) | 26.6 mm | Standard Deviation 23.2 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 12 (n=44,51) | -26.7 mm | Standard Deviation 24.2 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 36 (n=38,46) | -29.7 mm | Standard Deviation 25.9 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Week 24 (n=438,48) | 31.4 mm | Standard Deviation 25.9 |
| Tocilizumab | Patient Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 48 (n=35,45) | -31.7 mm | Standard Deviation 23.3 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Double-Blind Treatment Period | Baseline (n=49,51) | 60.2 mm | Standard Deviation 20 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Double-Blind Treatment Period | Week 4 (n=49,53) | 49.1 mm | Standard Deviation 24.6 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Double-Blind Treatment Period | Change at Week 4 (n=49,51) | -11.1 mm | Standard Deviation 25.6 |
| Tocilizumab | Patient Global Assessment of Pain During the Double-Blind Treatment Period | Week 4 (n=49,53) | 46.4 mm | Standard Deviation 27 |
| Tocilizumab | Patient Global Assessment of Pain During the Double-Blind Treatment Period | Change at Week 4 (n=49,51) | -7.3 mm | Standard Deviation 22.8 |
| Tocilizumab | Patient Global Assessment of Pain During the Double-Blind Treatment Period | Baseline (n=49,51) | 54.6 mm | Standard Deviation 21.8 |
p-value: 0.434t-test, 1 sided
Secondary
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
Population: ITT Population; 3 participants were randomized to the placebo treatment group but received tocilizumab. n=number of participants assessed at a specific visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 24 (n=43,50) | 26.2 mm | Standard Deviation 21.3 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 36 (n=38,45) | -25.6 mm | Standard Deviation 31 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 12 (n=45,51) | 29.6 mm | Standard Deviation 23.9 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 48 (n=36,45) | 22.1 mm | Standard Deviation 22.9 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 24 (n=42,49) | -25.0 mm | Standard Deviation 29.2 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 48 (n=35,44) | -28.0 mm | Standard Deviation 29.7 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 12 (n=44,50) | -20.3 mm | Standard Deviation 27.6 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 36 (n=39,46) | 23.1 mm | Standard Deviation 17.2 |
| Placebo, Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Baseline (n=46,54) | 48.9 mm | Standard Deviation 24.5 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 12 (n=44,50) | -22.2 mm | Standard Deviation 26.2 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Baseline (n=46,54) | 55.1 mm | Standard Deviation 22.2 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 24 (n=43,50) | 27.7 mm | Standard Deviation 25.2 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 24 (n=42,49) | -25.9 mm | Standard Deviation 22 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 36 (n=39,46) | 25.0 mm | Standard Deviation 21.3 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 36 (n=38,45) | -28.3 mm | Standard Deviation 27.4 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 48 (n=36,45) | 23.0 mm | Standard Deviation 20.4 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Change at Week 48 (n=35,44) | -30.4 mm | Standard Deviation 25.8 |
| Tocilizumab | Patient Global Assessment of Pain During the Open Treatment Period | Week 12 (n=45,51) | 32.8 mm | Standard Deviation 24 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Baseline (n=103) | 74 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 8 (n=99) | 74 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 12 (n=97) | 71 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 16 (n=95) | 71 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 20 (n=93) | 70 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 24 (n=93) | 71 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 28 (n=91) | 68 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 32 (n=90) | 68 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 36 (n=85) | 69 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 40 (n=82) | 65 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 44 (n=82) | 60 percentage of participants |
| Placebo, Tocilizumab | Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period | Week 48 (n=82) | 60 percentage of participants |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 1 (n=38,44) | 2.2 percent change | Standard Deviation 18.1 |
| Placebo, Tocilizumab | Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 4 (n=37,44) | -2.3 percent change | Standard Deviation 14.1 |
| Tocilizumab | Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 1 (n=38,44) | 4.2 percent change | Standard Deviation 19.6 |
| Tocilizumab | Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period | Week 4 (n=37,44) | -0.8 percent change | Standard Deviation 19.4 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period | Week 1 (n=44,52) | 19.2 percent change | Standard Deviation 70.1 |
| Placebo, Tocilizumab | Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period | Week 4 (n=46,52) | 18.3 percent change | Standard Deviation 95.6 |
| Tocilizumab | Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period | Week 1 (n=44,52) | -66.2 percent change | Standard Deviation 31.8 |
| Tocilizumab | Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period | Week 4 (n=46,52) | -47.0 percent change | Standard Deviation 95.9 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment | Week 1 (n=49,53) | 8.7 percent change | Standard Deviation 56.4 |
| Placebo, Tocilizumab | Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment | Week 4 (n=48,52) | 11.5 percent change | Standard Deviation 64.1 |
| Tocilizumab | Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment | Week 1 (n=49,53) | -51.2 percent change | Standard Deviation 32.8 |
| Tocilizumab | Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment | Week 4 (n=48,52) | -65.9 percent change | Standard Deviation 28.4 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period | Week 1 (n=48,51) | 24.6 percent change | Standard Deviation 29 |
| Placebo, Tocilizumab | Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period | Week 4 (n=49,52) | 37.7 percent change | Standard Deviation 77.1 |
| Tocilizumab | Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period | Week 1 (n=48,51) | 22.7 percent change | Standard Deviation 61.5 |
| Tocilizumab | Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period | Week 4 (n=49,52) | 41.7 percent change | Standard Deviation 167.9 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period | Week 1 (n=22,28) | 59.5 percent change | Standard Deviation 247.9 |
| Placebo, Tocilizumab | Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period | Week 4 (n=21,26) | -5.8 percent change | Standard Deviation 39.3 |
| Tocilizumab | Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period | Week 4 (n=21,26) | -35.5 percent change | Standard Deviation 61 |
| Tocilizumab | Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period | Week 1 (n=22,28) | -41.2 percent change | Standard Deviation 61.3 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | -12.0 percent change | Standard Deviation 54 |
| Placebo, Tocilizumab | Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | -1.1 percent change | Standard Deviation 53.7 |
| Tocilizumab | Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | -10.9 percent change | Standard Deviation 70.6 |
| Tocilizumab | Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | -27.3 percent change | Standard Deviation 47.6 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | -9.2 percent change | Standard Deviation 58.1 |
| Placebo, Tocilizumab | Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 7.7 percent change | Standard Deviation 73.8 |
| Tocilizumab | Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | -19.2 percent change | Standard Deviation 45.3 |
| Tocilizumab | Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | -30.0 percent change | Standard Deviation 45.9 |
Secondary
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
Population: One-Year Efficacy Population: all randomized participants with at least 1 tocilizumab infusion (completed or not). n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound | Week 12 (n=94) | -15.0 percent change | Standard Deviation 81.9 |
| Placebo, Tocilizumab | Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound | Week 24 (n=87) | -30.5 percent change | Standard Deviation 64.4 |
| Placebo, Tocilizumab | Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound | Week 48 (n=77) | -43.7 percent change | Standard Deviation 67 |
Secondary
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
Population: One-Year Efficacy Population: all randomized participants with at least 1 tocilizumab infusion (completed or not). n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound | Week 12 (n=94) | 121.0 percent change | Standard Deviation 573 |
| Placebo, Tocilizumab | Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound | Week 24 (n=87) | -23.5 percent change | Standard Deviation 92.8 |
| Placebo, Tocilizumab | Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound | Week 48 (n=77) | 3.6 percent change | Standard Deviation 263.2 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 3.4 percent change | Standard Deviation 74.4 |
| Placebo, Tocilizumab | Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 25.7 percent change | Standard Deviation 180.4 |
| Tocilizumab | Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 16.7 percent change | Standard Deviation 266.7 |
| Tocilizumab | Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 9.3 percent change | Standard Deviation 268.6 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | -2.6 percent change | Standard Deviation 59.5 |
| Placebo, Tocilizumab | Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | -1.5 percent change | Standard Deviation 63.5 |
| Tocilizumab | Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | -22.1 percent change | Standard Deviation 39.6 |
| Tocilizumab | Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | -23.1 percent change | Standard Deviation 49.3 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period | Week 4 (n=50,52) | 49.2 mm | Standard Deviation 18.1 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period | Change at Week 4 (n=50,52) | -11.6 mm | Standard Deviation 19.3 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period | Baseline (n=50,53) | 60.8 mm | Standard Deviation 17.2 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period | Baseline (n=50,53) | 58.4 mm | Standard Deviation 15.3 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period | Week 4 (n=50,52) | 44.6 mm | Standard Deviation 22.5 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period | Change at Week 4 (n=50,52) | -14.3 mm | Standard Deviation 20.7 |
Comparison: Change at Week 4p-value: 0.502Student t-test
Secondary
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
Population: ITT Population; 3 participants were randomized to the placebo treatment group but received tocilizumab. n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Baseline (n=47,56) | 49.3 mm | Standard Deviation 18.6 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 12 (n=44,51) | 32.9 mm | Standard Deviation 20.4 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 12 (n=44,51) | -16.5 mm | Standard Deviation 23.9 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 24 (n=42,50) | 24.3 mm | Standard Deviation 17 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 24 (n=42,50) | -27.4 mm | Standard Deviation 21.3 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 36 (n=38,46) | 22.7 mm | Standard Deviation 16.5 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 36 (n=38,46) | -28.4 mm | Standard Deviation 20.7 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 48 (n=37,44) | 16.4 mm | Standard Deviation 15.8 |
| Placebo, Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 48 (n=37,44) | -35.0 mm | Standard Deviation 23 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 36 (n=38,46) | -34.9 mm | Standard Deviation 23.1 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Baseline (n=47,56) | 59.6 mm | Standard Deviation 16.3 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 36 (n=38,46) | 23.1 mm | Standard Deviation 20.6 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 12 (n=44,51) | 28.3 mm | Standard Deviation 21.7 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 48 (n=37,44) | -39.4 mm | Standard Deviation 19.7 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 12 (n=44,51) | -30.8 mm | Standard Deviation 21.7 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Change at Week 24 (n=42,50) | -34.9 mm | Standard Deviation 21.3 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 24 (n=42,50) | 24.7 mm | Standard Deviation 21.1 |
| Tocilizumab | Physician Global Assessment of Disease Activity During the Open Treatment Period | Week 48 (n=37,44) | 19.3 mm | Standard Deviation 18.2 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Serum Amyloid A Component During the Double-Blind Treatment Period | Week 1 (n=26,29) | 89.5 mg/L | Standard Deviation 271.2 |
| Placebo, Tocilizumab | Serum Amyloid A Component During the Double-Blind Treatment Period | Week 4 (n=25,27) | 61.2 mg/L | Standard Deviation 169.2 |
| Placebo, Tocilizumab | Serum Amyloid A Component During the Double-Blind Treatment Period | Baseline (n=23,32) | 72.0 mg/L | Standard Deviation 221.9 |
| Tocilizumab | Serum Amyloid A Component During the Double-Blind Treatment Period | Week 1 (n=26,29) | 6.7 mg/L | Standard Deviation 3.6 |
| Tocilizumab | Serum Amyloid A Component During the Double-Blind Treatment Period | Week 4 (n=25,27) | 8.9 mg/L | Standard Deviation 10.4 |
| Tocilizumab | Serum Amyloid A Component During the Double-Blind Treatment Period | Baseline (n=23,32) | 57.9 mg/L | Standard Deviation 108.2 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Serum Amyloid A Component During the Open Treatment Period | Baseline (n=58) | 58.6 mg/L | Standard Deviation 135.9 |
| Placebo, Tocilizumab | Serum Amyloid A Component During the Open Treatment Period | Week 12 (n=46) | 40.3 mg/L | Standard Deviation 218.7 |
| Placebo, Tocilizumab | Serum Amyloid A Component During the Open Treatment Period | Week 24 (n=46) | 13.3 mg/L | Standard Deviation 41.6 |
| Placebo, Tocilizumab | Serum Amyloid A Component During the Open Treatment Period | Week 36 (n=38) | 7.3 mg/L | Standard Deviation 6.3 |
| Placebo, Tocilizumab | Serum Amyloid A Component During the Open Treatment Period | Week 48 (n=37) | 5.7 mg/L | Standard Deviation 3 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period | Baseline (n=103) | 3.97 pmol/L | Standard Deviation 1.27 |
| Placebo, Tocilizumab | Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period | Week 12 (n=93) | 3.94 pmol/L | Standard Deviation 1.2 |
| Placebo, Tocilizumab | Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period | Week 48 (n=77) | 3.90 pmol/L | Standard Deviation 1.21 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | 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, Baseline (n=103) | 5.59 ng/mL | Standard Deviation 2.06 |
| Placebo, Tocilizumab | 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, Week 12 (n=94) | 6.07 ng/mL | Standard Deviation 2.39 |
| Placebo, Tocilizumab | 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, Week 24 (n=85) | 5.74 ng/mL | Standard Deviation 2.27 |
| Placebo, Tocilizumab | 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, Week 48 (n=77) | 5.86 ng/mL | Standard Deviation 2.12 |
| Placebo, Tocilizumab | 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-CTX-I, Baseline (n=103) | 0.35 ng/mL | Standard Deviation 0.22 |
| Placebo, Tocilizumab | 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-CTX-I, Week 12 (n=93) | 0.35 ng/mL | Standard Deviation 0.2 |
| Placebo, Tocilizumab | 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-CTX-I, Week 48 (n=77) | 0.33 ng/mL | Standard Deviation 0.18 |
| Placebo, Tocilizumab | 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-PINP, Week 48 (n=77) | 53.16 ng/mL | Standard Deviation 30.14 |
| Placebo, Tocilizumab | 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-PINP, Baseline (n=103) | 41.15 ng/mL | Standard Deviation 23.95 |
| Placebo, Tocilizumab | 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-PINP, Week 12 (n=93) | 52.33 ng/mL | Standard Deviation 32.66 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 10.1 swollen joints | Standard Deviation 5 |
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 8.7 swollen joints | Standard Deviation 5.3 |
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 9.8 swollen joints | Standard Deviation 6 |
| Tocilizumab | SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 10.4 swollen joints | Standard Deviation 5.1 |
| Tocilizumab | SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 8.0 swollen joints | Standard Deviation 5.3 |
| Tocilizumab | SJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 6.7 swollen joints | Standard Deviation 4.5 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Open Treatment Period | Baseline (n=103) | 10.2 swollen joints | Standard Deviation 5.7 |
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Open Treatment Period | Week 12 (n=97) | 4.4 swollen joints | Standard Deviation 4.7 |
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Open Treatment Period | Week 24 (n=92) | 3.5 swollen joints | Standard Deviation 3.7 |
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Open Treatment Period | Week 36 (n=84) | 2.5 swollen joints | Standard Deviation 3.3 |
| Placebo, Tocilizumab | SJC Based on 40-Joint Count During the Open Treatment Period | Week 48 (n=82) | 2.1 swollen joints | Standard Deviation 3 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period | P-Dkk1, Week 12 (n=86) | 572.45 pg/mL | Standard Deviation 350.85 |
| Placebo, Tocilizumab | S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period | S-Sclerostin, Baseline (n=103) | 0.51 pg/mL | Standard Deviation 0.22 |
| Placebo, Tocilizumab | S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period | S-Sclerostin, Week 12 (n=93) | 0.55 pg/mL | Standard Deviation 0.2 |
| Placebo, Tocilizumab | S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period | S-Sclerostin, Week 24 (n=84) | 0.51 pg/mL | Standard Deviation 0.19 |
| Placebo, Tocilizumab | S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period | S-Sclerostin, Week 48 (n=75) | 0.54 pg/mL | Standard Deviation 0.21 |
| Placebo, Tocilizumab | S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period | P-Dkk1, Baseline (n=102) | 847.50 pg/mL | Standard Deviation 610.22 |
| Placebo, Tocilizumab | S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period | P-Dkk1, Week 48 (n=72) | 685.79 pg/mL | Standard Deviation 482.73 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 8.3 swollen joints | Standard Deviation 4.2 |
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 7.7 swollen joints | Standard Deviation 4.6 |
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 6.9 swollen joints | Standard Deviation 4.4 |
| Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 8.5 swollen joints | Standard Deviation 4.5 |
| Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 7.0 swollen joints | Standard Deviation 4.8 |
| Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 5.8 swollen joints | Standard Deviation 3.8 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period | Baseline (n=103) | 8.2 swollen joints | Standard Deviation 4.6 |
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period | Week 12 (n=97) | 3.8 swollen joints | Standard Deviation 4 |
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period | Week 24 (n=92) | 3.1 swollen joints | Standard Deviation 3.4 |
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period | Week 36 (n=84) | 2.2 swollen joints | Standard Deviation 3 |
| Placebo, Tocilizumab | Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period | Week 48 (n=82) | 1.7 swollen joints | Standard Deviation 2.6 |
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Week 1 (n=49,53) | 26.4 units on a scale | Standard Deviation 19.1 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Week 4 (n=48,52) | 26.3 units on a scale | Standard Deviation 18.9 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Change at Week 1 (n=49,53) | -0.1 units on a scale | Standard Deviation 7.1 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Change at Week 4 (n=48,52) | 0.8 units on a scale | Standard Deviation 7.8 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Baseline (n=50,53) | 26.4 units on a scale | Standard Deviation 17.2 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Change at Week 4 (n=48,52) | -4.4 units on a scale | Standard Deviation 10 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Baseline (n=50,53) | 25.8 units on a scale | Standard Deviation 16.8 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Week 1 (n=49,53) | 25.3 units on a scale | Standard Deviation 17.6 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Change at Week 1 (n=49,53) | -0.6 units on a scale | Standard Deviation 7.1 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound | Week 4 (n=48,52) | 21.8 units on a scale | Standard Deviation 15.5 |
Comparison: Change at Week 1p-value: 0.692Wilcoxon (Mann-Whitney)
Comparison: Change at Week 4p-value: 0.019Wilcoxon (Mann-Whitney)
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Week 1 (n=49,53) | 9.6 units on a scale | Standard Deviation 11.9 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Week 4 (n=48,52) | 10.0 units on a scale | Standard Deviation 13.2 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Change at Week 1 (n=49,53) | -0.3 units on a scale | Standard Deviation 3.5 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Change at Week 4 (n=48,52) | 0.8 units on a scale | Standard Deviation 7.7 |
| Placebo, Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Baseline (n=50,53) | 10.1 units on a scale | Standard Deviation 11.2 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Change at Week 4 (n=48,52) | -2.0 units on a scale | Standard Deviation 5.1 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Baseline (n=50,53) | 10.2 units on a scale | Standard Deviation 11.4 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Week 1 (n=49,53) | 8.9 units on a scale | Standard Deviation 12.3 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Change at Week 1 (n=49,53) | -1.4 units on a scale | Standard Deviation 4.9 |
| Tocilizumab | Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound | Week 4 (n=48,52) | 8.4 units on a scale | Standard Deviation 12.1 |
Comparison: Change at Week 1p-value: 0.137Wilcoxon (Mann-Whitney)
Comparison: Change at Week 4p-value: 0.043Wilcoxon (Mann-Whitney)
Secondary
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
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 12.0 tender joints | Standard Deviation 6.6 |
| Placebo, Tocilizumab | Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 11.0 tender joints | Standard Deviation 7.1 |
| Placebo, Tocilizumab | Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 10.6 tender joints | Standard Deviation 6.7 |
| Tocilizumab | Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 13.4 tender joints | Standard Deviation 6.7 |
| Tocilizumab | Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 10.6 tender joints | Standard Deviation 6.7 |
| Tocilizumab | Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 9.9 tender joints | Standard Deviation 7.7 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | TJC Based on 28-Joint Count During the Open Treatment Period | Baseline (n=103) | 12.3 tender joints | Standard Deviation 6.9 |
| Placebo, Tocilizumab | TJC Based on 28-Joint Count During the Open Treatment Period | Week 12 (n=97) | 5.5 tender joints | Standard Deviation 5.6 |
| Placebo, Tocilizumab | TJC Based on 28-Joint Count During the Open Treatment Period | Week 24 (n=92) | 4.0 tender joints | Standard Deviation 4.7 |
| Placebo, Tocilizumab | TJC Based on 28-Joint Count During the Open Treatment Period | Week 36 (n=84) | 3.6 tender joints | Standard Deviation 4.5 |
| Placebo, Tocilizumab | TJC Based on 28-Joint Count During the Open Treatment Period | Week 48 (n=82) | 3.3 tender joints | Standard Deviation 4.7 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit. Changes from baseline were described for participants without missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 17.7 tender joints | Standard Deviation 9.1 |
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 16.3 tender joints | Standard Deviation 9.9 |
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 15.0 tender joints | Standard Deviation 8.6 |
| Tocilizumab | TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Baseline (n=50,53) | 18.3 tender joints | Standard Deviation 8 |
| Tocilizumab | TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 1 (n=49,53) | 14.6 tender joints | Standard Deviation 9.4 |
| Tocilizumab | TJC Based on 40-Joint Count During the Double-Blind Treatment Period | Week 4 (n=50,53) | 14.0 tender joints | Standard Deviation 10.7 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Open Treatment Period | Baseline (n=103) | 17.0 tender joints | Standard Deviation 8.7 |
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Open Treatment Period | Week 24 (n=92) | 5.9 tender joints | Standard Deviation 6.5 |
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Open Treatment Period | Week 36 (n=84) | 5.2 tender joints | Standard Deviation 6.2 |
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Open Treatment Period | Week 48 (n=82) | 5.0 tender joints | Standard Deviation 6.5 |
| Placebo, Tocilizumab | TJC Based on 40-Joint Count During the Open Treatment Period | Week 12 (n=97) | 7.9 tender joints | Standard Deviation 7.7 |
Secondary
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
Population: One-Year Efficacy Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Tocilizumab | Weekly Methotrexate (MTX) Dose | Baseline (n=103) | 17.7 mg/week | Standard Deviation 4.2 |
| Placebo, Tocilizumab | Weekly Methotrexate (MTX) Dose | Week 24 (n=91) | 17.1 mg/week | Standard Deviation 4.4 |
| Placebo, Tocilizumab | Weekly Methotrexate (MTX) Dose | Week 48 (n=77) | 16.9 mg/week | Standard Deviation 4.6 |