Rheumatoid Arthritis
Conditions
Brief summary
This single-arm study evaluated the long-term efficacy and safety of tocilizumab in participants who had completed treatment in the tocilizumab core studies (NCT00106522 \[Roche protocol WA18062\], NCT00106574 \[Roche protocol WA18063\], and NCT00109408 \[Roche protocol WA17824\]) of adults with rheumatoid arthritis. Participants received tocilizumab alone or in combination with standard anti-rheumatic treatment.
Interventions
DRUGTocilizumab
For participants weighing \> 100 kg, the maximum dose of tocilizumab was 800 mg. Tocilizumab was supplied as a sterile solution in vials.
Disease-modifying anti-rheumatic drugs included methotrexate, chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These drugs could be used alone or in combination, except for the combination of methotrexate and leflunomide, which was not allowed.
Participants could be treated with non-steroidal anti-inflammatory drugs up to the maximum recommended dose throughout the study. The choice and doses of non-steroidal anti-inflammatory drugs were at the discretion of the investigator.
Oral corticosteroids (≤ 10 mg/day) were permitted during the study.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have completed participation in 1 of the core studies in adult rheumatoid arthritis.
Exclusion criteria
* Treatment with any investigational agent since the last administration of study drug in the core studies. * Treatment with iv gamma globulin, plasmapheresis, or prosorba column since the last administration of study drug in the core studies. * Treatment with an anti-TNF or anti-IL1 agent, a T-cell co-stimulation modulator, or any biologic since the last administration of study drug in the core studies. * Immunization with a live/attenuated vaccine since the last administration of study drug in the core studies. * Previous treatment with any cell-depleting therapies, including investigational agents. * Parenteral, intramuscular, or intra-articular corticosteroids within 6 weeks prior to baseline in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With ≥ 1 Adverse Event | Baseline to the end of the study (up to 7 years, 7 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Concomitant Oral Corticosteroid Therapy | Baseline to the end of the study (up to 7 years, 7 months) | Concomitant therapy with oral corticosteroids (up 5 to 10 mg daily prednisone or equivalent) was permitted in the study. Reduction of oral corticosteroids was permitted, but not required, if a patient achieved at least a 50% improvement from baseline in both tender joint count and swollen joint count. The data are reported for each 6-month period of the study where a month = 28 days. The last 6-month period is for months 96 through 101. The actually study duration in 28-day months was 98.85 months. |
| Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Baseline to Week 296 | Participants who entered this study from study WA17824 on tocilizumab monotherapy, who did not achieve a 50% reduction in tender and swollen joint counts from Baseline of study WA17824, could add methotrexate or another allowable disease-modifying anti-rheumatic drug, according to the investigator's practice and as tolerated by the patient, at any time during this study. |
| Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | Baseline to Week 264 | Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale no disease activity \[symptom-free and no arthritis symptoms\], right end of the scale maximum disease activity); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale no pain, right end of the scale unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate. |
| Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264 | Baseline to Week 264 | A major clinical response was defined as maintenance of an improvement of at least 70% in the American College of Rheumatology (ACR) score (ACR70) for at least 24 weeks. Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale no disease activity \[symptom-free and no arthritis symptoms\], right end of the scale maximum disease activity); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale no pain, right end of the scale unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate. |
| Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | Baseline to Week 264 | Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale no disease activity \[symptom-free and no arthritis symptoms\], right end of the scale maximum disease activity); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale no pain, right end of the scale unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate. |
| Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline to Week 264 | The number of swollen (66 assessed joints) and tender (68 assessed joints) joints was assessed. Joints were physically examined and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. |
| Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline to Week 264 | Participant's made a global assessment of their current disease activity on a 100 mm horizontal visual analogue scale (VAS). The left end of the scale indicated no disease activity (symptom-free and no arthritis symptoms, score = 0) and the right end indicated maximum disease activity (maximum arthritis disease activity, score = 100). The participant's treating physician made a global assessment of the participant's current disease activity on a 100 mm horizontal VAS. The left end of the scale indicated no disease activity (symptom-free and no arthritis symptoms, score = 0) and the right end indicated maximum disease activity (maximum arthritis disease activity, score = 100). Participant's made an assessment of their current level of pain on a 100 mm horizontal VAS. The left end of the scale indicated no pain (score = 0) and the right end of the scale indicated unbearable pain (score = 100). |
| Percentage of Participants Who Withdrew From Treatment | Baseline to the end of the study (up to 7 years, 7 months) | — |
| Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline to Week 264 | Erythrocyte sedimentation rate (ESR) was determined locally. |
| Change in the Disease Activity Score 28 (DAS-28) From Baseline to Weeks 24, 48, 96, and 264 | Baseline to Week 264 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. |
| Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Baseline to Week 264 | A DAS-28 responder was defined as someone who met the European League Against Rheumatism \[EULAR\] criteria of a good or moderate response. A change of the DAS-28 score from Baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score \> 3.2 to ≤ 5.1, a change from baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score \> 5.1, a change from baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores \> 3.2. |
| Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Baseline to Week 264 | A DAS-28 responder was defined as someone who met the European League Against Rheumatism \[EULAR\] criteria of a good or moderate response. A change of the DAS-28 score from Baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score \> 3.2 to ≤ 5.1, a change from baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score \> 5.1, a change from baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores \> 3.2. |
| Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Baseline to Week 264 | The FACIT-F is a 13-item participant self-report questionnaire that assesses fatigue over the previous 7 days by scoring each item on a 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). An overall FACIT-F score was obtained by summing the scores of all 13 items. The overall score ranged from 0 to 52. A lower score indicates less fatigue. A clinically relevant improvement in the FACIT-F score was defined as a ≥ 5-point increase from Baseline. |
| Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Baseline to Week 264 | The SF-36 Health Survey uses participant-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A clinically relevant improvement in the Physical and Mental Component Scores of the SF-36 was defined as a ≥ 5-point increase from Baseline. |
| Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline to Week 264 | The Health Assessment Questionnaire-Disability Index (HAQ-DI), as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The HAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Costa Rica, Czechia, Denmark, Finland, France, Germany, Hong Kong, Iceland, Israel, Italy, Lithuania, Mexico, Netherlands, Norway, Panama, Peru, Portugal, Puerto Rico, Russia, Serbia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants received tocilizumab 8 mg/kg intravenously every 4 weeks till the end of the study (up to 7 years, 7 months). In addition, participants may have also received disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drugs, and oral corticosteroids at the discretion of the investigator. | 2,067 |
| Total | 2,067 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 304 |
| Overall Study | Death | 39 |
| Overall Study | Failure to Return | 46 |
| Overall Study | Insufficient Therapeutic Response | 129 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Reason not Specified | 83 |
| Overall Study | Refused Treatment | 151 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 52.2 years STANDARD_DEVIATION 12.6 |
| Sex: Female, Male Female | 1689 Participants |
| Sex: Female, Male Male | 378 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1,836 / 2,067 |
| serious Total, serious adverse events | 727 / 2,067 |
Outcome results
Primary
Percentage of Participants With ≥ 1 Adverse Event
Time frame: Baseline to the end of the study (up to 7 years, 7 months)
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With ≥ 1 Adverse Event | 96.3 Percentage of participants |
Secondary
Change in the Disease Activity Score 28 (DAS-28) From Baseline to Weeks 24, 48, 96, and 264
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Change in the Disease Activity Score 28 (DAS-28) From Baseline to Weeks 24, 48, 96, and 264 | Week 264 (n = 1278) | -3.73 Units on a scale | Standard Deviation 1.742 |
| Tocilizumab | Change in the Disease Activity Score 28 (DAS-28) From Baseline to Weeks 24, 48, 96, and 264 | Week 24 (n = 1920) | -2.82 Units on a scale | Standard Deviation 1.559 |
| Tocilizumab | Change in the Disease Activity Score 28 (DAS-28) From Baseline to Weeks 24, 48, 96, and 264 | Week 48 (n = 1753) | -3.20 Units on a scale | Standard Deviation 1.644 |
| Tocilizumab | Change in the Disease Activity Score 28 (DAS-28) From Baseline to Weeks 24, 48, 96, and 264 | Week 96 (n = 1596) | -3.46 Units on a scale | Standard Deviation 1.715 |
Secondary
Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264
Participant's made a global assessment of their current disease activity on a 100 mm horizontal visual analogue scale (VAS). The left end of the scale indicated no disease activity (symptom-free and no arthritis symptoms, score = 0) and the right end indicated maximum disease activity (maximum arthritis disease activity, score = 100). The participant's treating physician made a global assessment of the participant's current disease activity on a 100 mm horizontal VAS. The left end of the scale indicated no disease activity (symptom-free and no arthritis symptoms, score = 0) and the right end indicated maximum disease activity (maximum arthritis disease activity, score = 100). Participant's made an assessment of their current level of pain on a 100 mm horizontal VAS. The left end of the scale indicated no pain (score = 0) and the right end of the scale indicated unbearable pain (score = 100).
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Physician Disease Activity - Baseline (n=2043) | 57.3 mm | Standard Deviation 22.04 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Disease Activity - Baseline (n=2039) | 60.5 mm | Standard Deviation 25.52 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Disease Activity - Week 24 (n=1989) | 34.4 mm | Standard Deviation 26.03 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Disease Activity - Week 48 (n=1840) | 31.7 mm | Standard Deviation 25.25 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Disease Activity - Week 108 (n=1621) | 29.2 mm | Standard Deviation 24.75 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Disease Activity - Week 156 (n=1515) | 28.5 mm | Standard Deviation 25.16 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Disease Activity - Week 204 (n=1427) | 27.4 mm | Standard Deviation 24.72 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Disease Activity - Week 264 (n=1328) | 27.4 mm | Standard Deviation 25.5 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Physician Disease Activity - Week 24 (n=1990) | 26.8 mm | Standard Deviation 20.22 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Physician Disease Activity - Week 48 (n=1830) | 22.3 mm | Standard Deviation 18.93 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Physician Disease Activity - Week 108 (n=1619) | 18.6 mm | Standard Deviation 17.59 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Physician Disease Activity - Week 156 (n=1516) | 17.4 mm | Standard Deviation 17.21 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Physician Disease Activity - Week 204 (n=1413) | 15.6 mm | Standard Deviation 16.49 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Physician Disease Activity - Week 264 (n=1330) | 15.1 mm | Standard Deviation 16.51 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Pain - Baseline (n=2041) | 54.9 mm | Standard Deviation 25 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Pain - Week 24 (n=1991) | 31.0 mm | Standard Deviation 24.56 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Pain - Week 48 (n=1842) | 28.0 mm | Standard Deviation 23.76 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Pain - Week 108 (n=1622) | 26.6 mm | Standard Deviation 23.52 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Pain - Week 156 (n=1517) | 26.2 mm | Standard Deviation 23.9 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Pain - Week 204 (n=1428) | 25.3 mm | Standard Deviation 23.05 |
| Tocilizumab | Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Participant Pain - Week 264 (n=1329) | 25.1 mm | Standard Deviation 23.72 |
Secondary
Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264
Erythrocyte sedimentation rate (ESR) was determined locally.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 264 (n = 1329) | 9.7 mm/h | Standard Deviation 13.51 |
| Tocilizumab | Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline (n = 2047) | 46.2 mm/h | Standard Deviation 27.45 |
| Tocilizumab | Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 24 (n = 1992) | 11.3 mm/h | Standard Deviation 14.97 |
| Tocilizumab | Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 48 (n = 1830) | 10.2 mm/h | Standard Deviation 13.94 |
| Tocilizumab | Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 108 (n = 1606) | 9.0 mm/h | Standard Deviation 12.79 |
| Tocilizumab | Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 156 (n = 1509) | 8.9 mm/h | Standard Deviation 12.44 |
| Tocilizumab | Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 204 (n = 1412) | 8.9 mm/h | Standard Deviation 12.01 |
Secondary
Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264
The Health Assessment Questionnaire-Disability Index (HAQ-DI), as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The HAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline (n = 2037) | 1.46 Units on a scale | Standard Deviation 0.66 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 24 (n = 2008) | 1.04 Units on a scale | Standard Deviation 0.692 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 48 (n = 1853) | 0.97 Units on a scale | Standard Deviation 0.693 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 108 (n = 1635) | 0.89 Units on a scale | Standard Deviation 0.694 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 156 (n = 1529) | 0.87 Units on a scale | Standard Deviation 0.689 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 204 (n = 1438) | 0.84 Units on a scale | Standard Deviation 0.684 |
| Tocilizumab | Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 264 (n = 1334) | 0.86 Units on a scale | Standard Deviation 0.696 |
Secondary
Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264
A major clinical response was defined as maintenance of an improvement of at least 70% in the American College of Rheumatology (ACR) score (ACR70) for at least 24 weeks. Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale no disease activity \[symptom-free and no arthritis symptoms\], right end of the scale maximum disease activity); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale no pain, right end of the scale unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264 | Week 144 (n = 1615) | 20.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264 | Week 192 (n = 1514) | 22.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264 | Week 48 (n = 1937) | 8.5 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264 | Week 96 (n = 1745) | 16.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264 | Week 264 (n = 1358) | 24.9 Percentage of participants |
Secondary
Percentage of Participants Who Changed From Monotherapy to Combination Therapy
Participants who entered this study from study WA17824 on tocilizumab monotherapy, who did not achieve a 50% reduction in tender and swollen joint counts from Baseline of study WA17824, could add methotrexate or another allowable disease-modifying anti-rheumatic drug, according to the investigator's practice and as tolerated by the patient, at any time during this study.
Time frame: Baseline to Week 296
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants from the core study WA17824 are included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 40 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 68 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 96 | 1.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 100 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 104 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 292 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 296 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 8 | 1.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 12 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 24 | 15.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 28 | 7.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 32 | 2.5 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 36 | 1.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 44 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 48 | 1.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 52 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 54 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 64 | 1.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 72 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 76 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 88 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 108 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 112 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 116 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 120 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 140 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 152 | 0.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 184 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 196 | 0.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Changed From Monotherapy to Combination Therapy | Week 200 | 0.8 Percentage of participants |
Secondary
Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264
A DAS-28 responder was defined as someone who met the European League Against Rheumatism \[EULAR\] criteria of a good or moderate response. A change of the DAS-28 score from Baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score \> 3.2 to ≤ 5.1, a change from baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score \> 5.1, a change from baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores \> 3.2.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 264: Maintained response 96 weeks (n = 1358) | 56.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 48: Maintained response 24 weeks (n=1937) | 67.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 96: Maintained response 24 weeks (n=1745) | 72.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 96: Maintained response 48 weeks (n=1745) | 63.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 144: Maintained response 24 weeks (n=1615) | 73.1 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 144: Maintained response 48 weeks (n=1615) | 64.1 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 144: Maintained response 96 weeks (n=1615) | 52.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 192: Maintained response 24 weeks (n=1514) | 73.3 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 192: Maintained response 48 weeks (n=1514) | 64.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 192: Maintained response 96 weeks (n=1514) | 53.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 192: Maintained response 144 weeks (n=1514) | 45.5 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 264: Maintained response 24 weeks (n = 1358) | 76.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 264: Maintained response 48 weeks (n = 1358) | 68.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 264: Maintained response 144 weeks (n = 1358) | 48.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264 | Week 264: Maintained response 192 weeks (n = 1358) | 42.1 Percentage of participants |
Secondary
Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264
Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale no disease activity \[symptom-free and no arthritis symptoms\], right end of the scale maximum disease activity); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale no pain, right end of the scale unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 96: Maintained 48 weeks (n=1745) | 43.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 144: Maintained 48 weeks (n=1615) | 48.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 144: Maintained 96 weeks (n=1615) | 35.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 192: Maintained 24 weeks (n=1514) | 60.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 192: Maintained 48 weeks (n=1514) | 52.3 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 96: Maintained 48 weeks (n=1745) | 22.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 192: Maintained 144 weeks (n=1514) | 15.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 96: Maintained 24 weeks (n=1745) | 16.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 144: Maintained 48 weeks (n=1615) | 15.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 192: Maintained 24 weeks (n=1514) | 22.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 264: Maintained 96 weeks (n=1358) | 14.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 264: Maintained 192 weeks (n=1358) | 7.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 48: Maintained 24 weeks (n=1937) | 41.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 96: Maintained 24 weeks (n=1745) | 53.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 144: Maintained 24 weeks (n=1615) | 56.3 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 192: Maintained 96 weeks (n=1514) | 41.3 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 192: Maintained 144 weeks (n=1514) | 31.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 264: Maintained 24 weeks (n=1358) | 63.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 264: Maintained 48 weeks (n=1358) | 54.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 264: Maintained 96 weeks (n=1358) | 46.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 264: Maintained 144 weeks (n=1358) | 38.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR20 Week 264: Maintained 192 weeks (n=1358) | 32.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 48: Maintained 24 weeks (n=1937) | 20.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 96: Maintained 24 weeks (n=1745) | 32.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 144: Maintained 24 weeks (n=1615) | 36.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 144: Maintained 48 weeks (n=1615) | 28.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 144: Maintained 96 weeks (n=1615) | 18.1 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 192: Maintained 24 weeks (n=1514) | 39.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 192: Maintained 48 weeks (n=1514) | 33.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 192: Maintained 96 weeks (n=1514) | 22.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 264: Maintained 24 weeks (n=1358) | 42.3 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 264: Maintained 48 weeks (n=1358) | 34.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 264: Maintained 96 weeks (n=1358) | 27.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 264: Maintained 144 weeks (n=1358) | 21.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR50 Week 264: Maintained 192 weeks (n=1358) | 16.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 48: Maintained 24 weeks (n=1937) | 8.5 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 96: Maintained 48 weeks (n=1745) | 11.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 144: Maintained 4 weeks (n=1615) | 20.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 144: Maintained 96 weeks (n=1615) | 8.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 192: Maintained 48 weeks (n=1514) | 17.6 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 192: Maintained 96 weeks (n=1514) | 11.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 192: Maintained 144 weeks (n=1514) | 7.3 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 264: Maintained 24 weeks (n=1358) | 24.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 264: Maintained 48 weeks (n=1358) | 19.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264 | ACR70 Week 264: Maintained 144 weeks (n=1358) | 11.0 Percentage of participants |
Secondary
Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264
A DAS-28 responder was defined as someone who met the European League Against Rheumatism \[EULAR\] criteria of a good or moderate response. A change of the DAS-28 score from Baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score \> 3.2 to ≤ 5.1, a change from baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score \> 5.1, a change from baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores \> 3.2.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 204 Good (n = 1358) | 67.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 24 Good (n = 1920) | 43.3 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 48 Good (n = 1753) | 51.9 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 108 Good (n = 1525) | 61.1 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 156 Good (n = 1441) | 64.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 264 Good (n = 1278) | 68.8 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 24 Moderate (n = 1920) | 45.1 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 48 Moderate (n = 1753) | 40.0 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 108 Moderate (n = 1525) | 33.2 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 156 Moderate (n = 1441) | 28.7 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 204 Moderate (n = 1358) | 26.4 Percentage of participants |
| Tocilizumab | Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264 | Week 264 Moderate (n = 1278) | 26.1 Percentage of participants |
Secondary
Percentage of Participants Who Withdrew From Treatment
Time frame: Baseline to the end of the study (up to 7 years, 7 months)
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Who Withdrew From Treatment | 36.6 Percentage of participants |
Secondary
Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264
The FACIT-F is a 13-item participant self-report questionnaire that assesses fatigue over the previous 7 days by scoring each item on a 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). An overall FACIT-F score was obtained by summing the scores of all 13 items. The overall score ranged from 0 to 52. A lower score indicates less fatigue. A clinically relevant improvement in the FACIT-F score was defined as a ≥ 5-point increase from Baseline.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Week 204 (n = 1422) | 56.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Week 264 (n = 1320) | 61.9 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Week 24 (n = 1984) | 59.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Week 36 (n = 1839) | 52.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Week 48 (n = 1803) | 56.0 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Week 108 (n = 1616) | 56.8 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264 | Week 156 (n = 1513) | 56.3 Percentage of participants |
Secondary
Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264
The SF-36 Health Survey uses participant-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A clinically relevant improvement in the Physical and Mental Component Scores of the SF-36 was defined as a ≥ 5-point increase from Baseline.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 24 Mental Score (n = 1850) | 42.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 156 Mental Score (n = 1468) | 46.1 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 24 Physical Score (n = 1850) | 56.2 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 48 Physical Score (n = 1789) | 61.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 156 Physical Score (n = 1468) | 62.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 204 Physical Score (n = 1377) | 64.1 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 48 Mental Score (n = 1789) | 44.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 108 Mental Score (n = 1551) | 45.3 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 204 Mental Score (n = 1377) | 47.1 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 264 Mental Score (n = 1302) | 44.9 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 108 Physical Score (n = 1551) | 63.2 Percentage of participants |
| Tocilizumab | Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264 | Week 264 Physical Score (n = 1302) | 63.7 Percentage of participants |
Secondary
Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264
Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale no disease activity \[symptom-free and no arthritis symptoms\], right end of the scale maximum disease activity); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale no pain, right end of the scale unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR50 Week 264 (n= 1319) | 58.8 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR20 Week 24 (n=1966) | 59.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR20 Week 48 (n=1825) | 66.7 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR20 Week 108 (n=1607) | 74.1 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR20 Week 156 (n=1512) | 74.3 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR20 Week 204 (n=1415) | 77.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR20 Week 264 (n = 1319) | 78.7 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR50 Week 24 (n=1966) | 34.9 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR50 Week 48 (n=1825) | 44.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR50 Week 108 (n=1607) | 52.8 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR50 Week 156 (n=1512) | 54.7 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR50 Week 204 (n=1415) | 56.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR70 Week 24 (n=1966) | 17.8 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR70 Week 48 (n=1825) | 25.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR70 Week 108 (n=1607) | 33.2 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR70 Week 156 (n=1512) | 35.7 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR70 Week 204 (n =1415) | 38.6 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR70 Week 264 (n=1319) | 40.5 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR90 Week 24 (n=1966) | 4.3 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR90 Week 48 (n=1825 | 7.9 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR90 Week 108 (n=1607) | 12.1 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR90 Week 156 (n=1512) | 14.7 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR90 Week 204 (n=1415) | 17.7 Percentage of participants |
| Tocilizumab | Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264 | ACR90 Week 264 (n=1319) | 18.1 Percentage of participants |
Secondary
Percentage of Participants With Concomitant Oral Corticosteroid Therapy
Concomitant therapy with oral corticosteroids (up 5 to 10 mg daily prednisone or equivalent) was permitted in the study. Reduction of oral corticosteroids was permitted, but not required, if a patient achieved at least a 50% improvement from baseline in both tender joint count and swollen joint count. The data are reported for each 6-month period of the study where a month = 28 days. The last 6-month period is for months 96 through 101. The actually study duration in 28-day months was 98.85 months.
Time frame: Baseline to the end of the study (up to 7 years, 7 months)
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 42 - 48 Months, n = 1568 | 50.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 0 - 6 Months, n = 2067 | 55.8 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 6 - 12 Months, n = 2041 | 55.3 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 12 - 18 Months, n = 1944 | 54.6 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 18 - 24 Months, n = 1832 | 54.3 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 24 - 30 Months, n = 1753 | 53.2 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 30 - 36 Months, n = 1677 | 52.9 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 36 - 42 Months, n = 1620 | 51.3 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 48 - 54 Months, n = 1516 | 50.6 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 54 - 60 Months, n = 1475 | 50.1 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 60 - 66 Months, n = 1423 | 49.2 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 66 - 72 Months, n = 1342 | 48.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 72 - 78 Months, n = 788 | 48.7 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 78 - 84 Months, n = 62 | 72.6 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 84 - 90 Months, n = 34 | 79.4 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 90 - 96 Months, n = 10 | 70.0 Percentage of participants |
| Tocilizumab | Percentage of Participants With Concomitant Oral Corticosteroid Therapy | 96 - 102 Months, n = 2 | 0.0 Percentage of participants |
Secondary
Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264
The number of swollen (66 assessed joints) and tender (68 assessed joints) joints was assessed. Joints were physically examined and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation.
Time frame: Baseline to Week 264
Population: All-exposure population: All participants who entered this study and received at least 1 dose of tocilizumab in either this extension study or in a core study. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline SJC (n = 2047) | 17.4 Joints | Standard Deviation 11.96 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 156 SJC (n = 1580) | 4.0 Joints | Standard Deviation 7.09 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 48 TJC (n = 1924) | 10.3 Joints | Standard Deviation 12.99 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 108 TJC (n = 1692) | 7.8 Joints | Standard Deviation 11.04 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 156 TJC (n = 1580) | 7.2 Joints | Standard Deviation 11.03 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 204 TJC (n = 1482) | 6.1 Joints | Standard Deviation 9.83 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 24 SJC (n = 2010) | 8.2 Joints | Standard Deviation 9.43 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 48 SJC (n = 1924) | 6.4 Joints | Standard Deviation 8.75 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 108 SJC (n = 1692) | 4.2 Joints | Standard Deviation 6.69 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 204 SJC (n = 1482) | 3.2 Joints | Standard Deviation 5.96 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 264 SJC (n = 1352) | 2.9 Joints | Standard Deviation 5.85 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Baseline TJC (n = 2047) | 27.3 Joints | Standard Deviation 16.97 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 24 TJC (n = 2010) | 12.8 Joints | Standard Deviation 14.1 |
| Tocilizumab | Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264 | Week 264 TJC (n = 1352) | 5.6 Joints | Standard Deviation 9.48 |