Rheumatoid Arthritis
Conditions
Brief summary
This prospective, multi-center, observational study will assess the efficacy and safety of treatment in patients who are treated with a TNF Inhibitor or RoActemra/Actemra (tocilizumab) as the first biologic therapy. Data will be collected for 52 weeks.
Interventions
None listed
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/=18 years of age * Diagnosis of rheumatoid arthritis * Non-respondent or intolerant to non-biologic disease-modifying anti-rheumatic drug (DMARD) therapy * Patient has been prescribed a first biologic therapy up to 6 weeks prior to the inclusion visit, irrespective of the treatment prescribed
Exclusion criteria
* Patients whose first biologic therapy is given as part of a clinical trial studying rheumatoid arthritis (RA) treatment * Patients who are receiving or have received experimental DMARDs as part of a clinical trial studying RA treatment in the last 12 months * Patients whose first biologic is rituximab, abatacept or anakinra. * Patients who have received any biologic therapy for more than 6 weeks prior to the inclusion visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Calculated Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 24 | Baseline and Week 24 | Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker \[erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/h), or C-reactive protein (CRP) in milligram/liter (mg/L)\]. For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of less than or equal to (\</=) 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Erythrocyte Sedimentation Rate | Baseline, Week 24, Week 52 | Blood samples were collected for ESR, which is an acute phase reactant and a measure of inflammation. BL = baseline. |
| Mean Change From Baseline in C-reactive Protein | Baseline, Week 24, Week 52 | Blood samples were collected for C-reactive protein (CRP). CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. |
| Mean Change From Baseline in Swollen Joint Count | Baseline, Week 24, Week 52 | A swollen joint count (SJC) is the most specific clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. 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. |
| Mean Change From Baseline in Tender Joint Count | Baseline, Week 24, Week 52 | A tender joint count (TJC) is the most specific clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. 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. |
| Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | Baseline, Week 24, Week 52 | Clinical Disease Activity Index (CDAI) was calculated as the sum of the following parameters: SJC + TJC + VAS Patient Global Assessment of Disease Activity + VAS Physician Global Assessment of Disease Activity. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity'. CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Simplified Disease Activity Index (SDAI) was calculated as the sum of the following parameters: SJC +TJC + Patient Global Assessment of Disease Activity + Physician Global Assessment of Disease Activity + CRP. SDAI scores ranged from 0 to 86, with higher scores also indicating increased disease activity. |
| Mean Change From Baseline in Physician Global Assessment Score | Baseline, Week 24, Week 52 | The Physician's Global Assessment of disease activity was assessed using a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). Change from baseline = scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. |
| Loss of Efficacy or Development of Intolerance to Biologic Therapy | Up to Week 52 | Events that are clearly consistent with the expected pattern of progression of the underlying disease may contribute to lack of efficacy. Lack of efficacy was one of the reasons for termination of biology therapy. The number of participants showing lack of efficacy to biologic therapy is presented. |
| Proportion of Participants Who Terminated Biologic Treatment | Up to Week 52 | The proportion of participants who discontinued biologic treatment was compared between tocilizumab-treated and TNF inhibitor-treated participants. |
| Reasons for Treatment Discontinuation | Up to Week 52 | The reasons for discontinuation of tocilizumab or TNF inhibitor is presented. |
| Mean Change From Baseline in Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 52 | Baseline and Week 52 | Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker (ESR in mm/h, or CRP in mg/L). For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of \</= 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity. |
| Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy | Up to Week 52 | An infusion reaction was defined as an adverse event (AE) occurring during and within 24 hours after the infusion, which may include hypersensitivity reactions or anaphylactic reactions. Injection site reactions were included in the summaries for infusion reactions. |
| Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | Up to Week 52 | An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. |
| Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study | Up to Week 52 | Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events. Based on seriousness criteria, they were categorized as serious and non-serious adverse events of special interest. |
| Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score | Baseline, Week 24, Week 52 | The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. |
| Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score | Baseline, Week 24, Week 52 | Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. 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. |
| Mean Change From Baseline in Visual Analogue Scale Pain Score | Baseline, Week 24, Week 52 | VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change from baseline =scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. |
| Shift From Baseline in Morning Stiffness | Baseline, Week 24, Week 52 | Shift tables presenting the number of participants in each bivariate category Week (W) 0 versus Week 24 and Week 52, with regards to morning stiffness at the different time points, was presented for each treatment arm. For participants who experienced joint stiffness while waking up in the morning, duration of morning stiffness was categorized as follows: Less than 30 minutes (min), Between 30 and 60 minutes, Between 60 and 120 minutes, Between 120 to 240 minutes, More than 240 minutes and the whole day. Baseline = BL |
| Change From Baseline in Patient Global Assessment of Disease Activity | Baseline, Week 24, Week 52 | The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A negative change from Baseline indicated improvement. |
| Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Up to end of treatment | The total number of participants who discontinued biologic therapy at the end of each study period (Week 0 - 24, Week 24 - 52, Week 52 - 57 and Week 57 - end of treatment) is presented. Participants who did not have a biologic therapy discontinuation or discontinued before having one, were considered as 'censored' at the date study termination. |
Countries
Argentina, Belgium, Colombia, Ecuador, Germany, Greece, Guatemala, Italy, Mexico, Panama, Portugal, Spain, Switzerland, Ukraine, United Kingdom, Uruguay
Participant flow
Recruitment details
This observational study was conducted at 158 sites in 16 countries from 9 February 2012 to 20 February 2015.
Pre-assignment details
A total of 1250 participants were screened for entry into the study, with 1225 participants enrolled in the study. One participant whose randomization status was unknown withdrew informed consent.
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants with rheumatoid arthritis who were currently being treated with tocilizumab as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. Tocilizumab administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed tocilizumab for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks. | 423 |
| TNF Inhibitor Participants with rheumatoid arthritis who were currently being treated with a TNF inhibitor as a first biologic therapy and were non-responders or intolerant to csDMARD therapy. The TNF inhibitor administration occurred as per routine practice and following the local prescribing information. Participants were observed for 52 weeks after initiation of the first biologic therapy. Participants who stopped treatment with the prescribed TNF inhibitor for reasons of inefficacy or intolerance continued to be observed for the planned period of 52 weeks. | 793 |
| Total | 1,216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 13 |
| Overall Study | Change of jobs | 0 | 1 |
| Overall Study | Incorrect medication received | 1 | 0 |
| Overall Study | Intolerance to the biologic treatment | 0 | 1 |
| Overall Study | Investigator did not wish to participate | 1 | 1 |
| Overall Study | Lack of Efficacy | 4 | 16 |
| Overall Study | Lost to Follow-up | 32 | 36 |
| Overall Study | Moved to other rheumatologic site | 0 | 1 |
| Overall Study | Participant consented to another study | 0 | 2 |
| Overall Study | Participant decision to stop treatment | 1 | 0 |
| Overall Study | Participant did not attend a visit | 1 | 0 |
| Overall Study | Participant did not complete last visit | 0 | 2 |
| Overall Study | Participant moved to another city | 2 | 0 |
| Overall Study | Participant moved to Scotland | 1 | 0 |
| Overall Study | Participant recruited after closing date | 0 | 1 |
| Overall Study | Participant transferred to another city | 1 | 0 |
| Overall Study | Participant went to United States | 1 | 0 |
| Overall Study | Participant will not return for visits | 0 | 2 |
| Overall Study | Participant withdrew informed consent | 8 | 10 |
| Overall Study | Probable overlap of RA with fibromyalgia | 1 | 0 |
| Overall Study | Refused to continue treatment | 7 | 0 |
| Overall Study | Screen failure | 1 | 0 |
| Overall Study | Site stopped participation | 5 | 1 |
Baseline characteristics
| Characteristic | Tocilizumab | TNF Inhibitor | Total |
|---|---|---|---|
| Age, Continuous | 54.26 years STANDARD_DEVIATION 12.75 | 55.16 years STANDARD_DEVIATION 13.05 | 54.85 years STANDARD_DEVIATION 12.95 |
| Sex: Female, Male Female | 351 Participants | 615 Participants | 966 Participants |
| Sex: Female, Male Male | 72 Participants | 178 Participants | 250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 132 / 423 | 231 / 793 |
| serious Total, serious adverse events | 22 / 423 | 64 / 793 |
Outcome results
Primary
Mean Change From Baseline in Calculated Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 24
Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker \[erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/h), or C-reactive protein (CRP) in milligram/liter (mg/L)\]. For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of less than or equal to (\</=) 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Baseline and Week 24
Population: Participants belonging to the safety population who had first biologic administration within 60 days after the last Rheumatoid Arthritis (RA) disease activity assessment were included in the effectiveness analysis population. Data of participants available at the time of the assessment were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tocilizumab | Mean Change From Baseline in Calculated Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 24 | -2.795 Units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Calculated Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 24 | -1.945 Units on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor: Analysis is based on an analysis of covariance (ANCOVA) model with change from baseline in DAS28-ESR at 24 weeks as dependent variable; therapy, site country, and treatment as fixed effects; DAS28-ESR at baseline as covariates.p-value: <0.00195% CI: [-1.112, -0.589]ANCOVA
Secondary
Change From Baseline in Patient Global Assessment of Disease Activity
The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Change From Baseline in Patient Global Assessment of Disease Activity | Change from BL to Week 24, n = 225, 423 | -29.633 scores on a scale |
| Tocilizumab | Change From Baseline in Patient Global Assessment of Disease Activity | Change from BL to Week 52, n = 206, 378 | -31.919 scores on a scale |
| TNF Inhibitor | Change From Baseline in Patient Global Assessment of Disease Activity | Change from BL to Week 24, n = 225, 423 | -24.525 scores on a scale |
| TNF Inhibitor | Change From Baseline in Patient Global Assessment of Disease Activity | Change from BL to Week 52, n = 206, 378 | -24.153 scores on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in Patient's Global Assessment of Disease as dependent variable; therapy and treatment as fixed effects; Patient's Global Assessment of Disease at baseline as covariates.p-value: 0.0195% CI: [-9.017, -1.2]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in Patient's Global Assessment of Disease as dependent variable; therapy and treatment as fixed effects; Patient's Global Assessment of Disease at baseline as covariates.p-value: <0.00195% CI: [-12.161, -3.372]ANCOVA
Secondary
Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period
The total number of participants who discontinued biologic therapy at the end of each study period (Week 0 - 24, Week 24 - 52, Week 52 - 57 and Week 57 - end of treatment) is presented. Participants who did not have a biologic therapy discontinuation or discontinued before having one, were considered as 'censored' at the date study termination.
Time frame: Up to end of treatment
Population: The safety population was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 0 -24 | 36 participants |
| Tocilizumab | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 24 - 52 | 61 participants |
| Tocilizumab | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 52 - 57 | 62 participants |
| Tocilizumab | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 57 - End of treatment | 63 participants |
| TNF Inhibitor | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 57 - End of treatment | 216 participants |
| TNF Inhibitor | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 0 -24 | 119 participants |
| TNF Inhibitor | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 52 - 57 | 212 participants |
| TNF Inhibitor | Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | Week 24 - 52 | 208 participants |
p-value: <0.001Log Rank
Secondary
Loss of Efficacy or Development of Intolerance to Biologic Therapy
Events that are clearly consistent with the expected pattern of progression of the underlying disease may contribute to lack of efficacy. Lack of efficacy was one of the reasons for termination of biology therapy. The number of participants showing lack of efficacy to biologic therapy is presented.
Time frame: Up to Week 52
Population: The safety population included all recruited participants who received at least one dose of a TNF inhibitor or tocilizumab during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Loss of Efficacy or Development of Intolerance to Biologic Therapy | 15 participants |
| TNF Inhibitor | Loss of Efficacy or Development of Intolerance to Biologic Therapy | 106 participants |
Secondary
Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score
Clinical Disease Activity Index (CDAI) was calculated as the sum of the following parameters: SJC + TJC + VAS Patient Global Assessment of Disease Activity + VAS Physician Global Assessment of Disease Activity. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity'. CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Simplified Disease Activity Index (SDAI) was calculated as the sum of the following parameters: SJC +TJC + Patient Global Assessment of Disease Activity + Physician Global Assessment of Disease Activity + CRP. SDAI scores ranged from 0 to 86, with higher scores also indicating increased disease activity.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | CDAI, Change from BL to Week 24, n = 176, 286 | -20.251 units on a scale |
| Tocilizumab | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | CDAI, Change from BL to Week 52, n = 162, 267 | -22.846 units on a scale |
| Tocilizumab | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | SDAI, Change from BL to Week 24, n = 93, 193 | -21.394 units on a scale |
| Tocilizumab | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | SDAI, Change from BL to Week 52, n = 91, 169 | -22.294 units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | SDAI, Change from BL to Week 52, n = 91, 169 | -19.048 units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | CDAI, Change from BL to Week 24, n = 176, 286 | -16.776 units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | SDAI, Change from BL to Week 24, n = 93, 193 | -18.164 units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | CDAI, Change from BL to Week 52, n = 162, 267 | -18.246 units on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for CDAI score at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in CDAI the dependent variable; therapy and treatment as fixed effects; CDAI at baseline as the covariate.p-value: <0.00195% CI: [-5.481, -1.469]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for CDAI score at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in CDAI as the dependent variable; therapy and treatment as fixed effects; CDAI at baseline as the covariate.p-value: <0.00195% CI: [-6.708, -2.492]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for SDAI score at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in SDAI as the dependent variable; therapy and treatment as fixed effects; SDAI at baseline as the covariate.p-value: 0.01495% CI: [-5.806, -0.652]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for SDAI score at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in SDAI as the dependent variable; therapy and treatment as fixed effects; SDAI at baseline as the covariate.p-value: 0.02795% CI: [-6.121, -0.37]ANCOVA
Secondary
Mean Change From Baseline in C-reactive Protein
Blood samples were collected for C-reactive protein (CRP). CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in C-reactive Protein | Change from BL to Week 24, n = 177, 396 | -11.005 mg/L |
| Tocilizumab | Mean Change From Baseline in C-reactive Protein | Change from BL to Week 52, n = 173, 348 | -6.332 mg/L |
| TNF Inhibitor | Mean Change From Baseline in C-reactive Protein | Change from BL to Week 24, n = 177, 396 | -4.333 mg/L |
| TNF Inhibitor | Mean Change From Baseline in C-reactive Protein | Change from BL to Week 52, n = 173, 348 | -5.216 mg/L |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for CRP at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in CRP as a dependent variable; therapy and treatment as fixed effects; CRP at baseline as the covariate.p-value: <0.00195% CI: [-10.271, -3.074]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for CRP at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in CRP as the dependent variable; therapy and treatment as fixed effects; CRP at baseline as the covariate.p-value: 0.65995% CI: [-6.074, 3.842]ANCOVA
Secondary
Mean Change From Baseline in Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 52
Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker (ESR in mm/h, or CRP in mg/L). For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of \</= 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Baseline and Week 52
Population: The effectiveness analysis population was used for analysis. Data of participants available at the time of the assessment were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tocilizumab | Mean Change From Baseline in Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 52 | -3.015 units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 52 | -2.105 units on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor: Analysis is based on an ANCOVA model with change from baseline to 12 months in DAS28-ESR as dependent variable; therapy and treatment as fixed effects; DAS28-ESR at baseline as covariates.p-value: <0.00195% CI: [-1.204, -0.617]ANCOVA
Secondary
Mean Change From Baseline in Erythrocyte Sedimentation Rate
Blood samples were collected for ESR, which is an acute phase reactant and a measure of inflammation. BL = baseline.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Erythrocyte Sedimentation Rate | Change from BL to Week 24, n = 225, 456 | -22.732 mm/hr |
| Tocilizumab | Mean Change From Baseline in Erythrocyte Sedimentation Rate | Change from BL to Week 52, n = 215, 411 | -21.515 mm/hr |
| TNF Inhibitor | Mean Change From Baseline in Erythrocyte Sedimentation Rate | Change from BL to Week 24, n = 225, 456 | -9.502 mm/hr |
| TNF Inhibitor | Mean Change From Baseline in Erythrocyte Sedimentation Rate | Change from BL to Week 52, n = 215, 411 | -8.868 mm/hr |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for ESR at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in ESR as a dependent variable; therapy and treatment as fixed effects; ESR at baseline as the covariate.p-value: <0.00195% CI: [-15.513, -10.947]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for ESR at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in ESR, as the dependent variable; therapy and treatment as fixed effects; ESR at baseline as the covariate.p-value: <0.00195% CI: [-15.419, -9.876]ANCOVA
Secondary
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. 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.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score | Change from BL to Week 24, n = 64, 86 | -7.153 scores on a scale |
| Tocilizumab | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score | Change from BL to Week 52, n = 50, 77 | -4.566 scores on a scale |
| TNF Inhibitor | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score | Change from BL to Week 24, n = 64, 86 | -3.260 scores on a scale |
| TNF Inhibitor | Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score | Change from BL to Week 52, n = 50, 77 | -1.779 scores on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in FACIT-F score as dependent variable; therapy and treatment as fixed effects; FACIT-F score at baseline as covariates.p-value: 0.03295% CI: [-7.457, -0.329]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in FACIT-F score as dependent variable; therapy and treatment as fixed effects; FACIT-F score at baseline as covariates.p-value: 0.16895% CI: [-6.763, 1.189]ANCOVA
Secondary
Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score
The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score | Change from BL to Week 24, n = 169, 301 | -0.591 Scores on a scale |
| Tocilizumab | Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score | Change from BL to Week 52, n = 152, 255 | -0.593 Scores on a scale |
| TNF Inhibitor | Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score | Change from BL to Week 24, n = 169, 301 | -0.445 Scores on a scale |
| TNF Inhibitor | Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score | Change from BL to Week 52, n = 152, 255 | -0.430 Scores on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in HAQ-DI as dependent variable; therapy and treatment as fixed effects; HAQ-DI at baseline as covariates.p-value: 0.0295% CI: [-0.269, -0.024]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in HAQ-DI as dependent variable; therapy and treatment as fixed effects; HAQ-DI at baseline as covariates.p-value: 0.0295% CI: [-0.301, -0.026]ANCOVA
Secondary
Mean Change From Baseline in Physician Global Assessment Score
The Physician's Global Assessment of disease activity was assessed using a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). Change from baseline = scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Physician Global Assessment Score | Change from BL to Week 24, n = 183, 300 | -35.581 scores on a scale |
| Tocilizumab | Mean Change From Baseline in Physician Global Assessment Score | Change from BL to Week 52, n = 174, 287 | -37.359 scores on a scale |
| TNF Inhibitor | Mean Change From Baseline in Physician Global Assessment Score | Change from BL to Week 24, n = 183, 300 | -26.551 scores on a scale |
| TNF Inhibitor | Mean Change From Baseline in Physician Global Assessment Score | Change from BL to Week 52, n = 174, 287 | -27.122 scores on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for Physician Global Assessment score at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in Physician Global Assessment of Disease Activity as the dependent variable; therapy and treatment as fixed effects; Physician Global Assessment of Disease Activity at baseline as covariates.p-value: <0.00195% CI: [-12.655, -5.404]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for Physician Global Assessment score at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in Physician Global Assessment of Disease Activity as the dependent variable; therapy and treatment as fixed effects; Physician Global Assessment of Disease Activity at baseline as covariates.p-value: <0.00195% CI: [-14.13, -6.345]ANCOVA
Secondary
Mean Change From Baseline in Swollen Joint Count
A swollen joint count (SJC) is the most specific clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. 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: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Swollen Joint Count | Change from BL to Week 24, n = 288, 554 | -5.698 Number of swollen joints |
| Tocilizumab | Mean Change From Baseline in Swollen Joint Count | Change from BL to Week 52, n = 258, 503 | -6.313 Number of swollen joints |
| TNF Inhibitor | Mean Change From Baseline in Swollen Joint Count | Change from BL to Week 24, n = 288, 554 | -5.122 Number of swollen joints |
| TNF Inhibitor | Mean Change From Baseline in Swollen Joint Count | Change from BL to Week 52, n = 258, 503 | -5.561 Number of swollen joints |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for SJC at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in SJC as the dependent variable; therapy and treatment as fixed effects; SJC at baseline as the covariate.p-value: 0.02495% CI: [-1.078, -0.075]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for SJC at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in SJC, as the dependent variable; therapy and treatment as fixed effects; SJC, at baseline as the covariate.p-value: 0.00295% CI: [-1.238, -0.267]ANCOVA
Secondary
Mean Change From Baseline in Tender Joint Count
A tender joint count (TJC) is the most specific clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. 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: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Tender Joint Count | Change from BL to Week 24, n = 289, 554 | -7.922 Number of tender joints |
| Tocilizumab | Mean Change From Baseline in Tender Joint Count | Change from BL to Week 52, n = 259, 501 | -8.421 Number of tender joints |
| TNF Inhibitor | Mean Change From Baseline in Tender Joint Count | Change from BL to Week 24, n = 289, 554 | -7.302 Number of tender joints |
| TNF Inhibitor | Mean Change From Baseline in Tender Joint Count | Change from BL to Week 52, n = 259, 501 | -7.205 Number of tender joints |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for TJC at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in TJC as the dependent variable; therapy and treatment as fixed effects; TJC at baseline as the covariate.p-value: 0.12395% CI: [-1.408, 0.169]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor for TJC at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in TJC as the dependent variable; therapy and treatment as fixed effects; TJC at baseline as the covariate.p-value: 0.00495% CI: [-2.039, -0.393]ANCOVA
Secondary
Mean Change From Baseline in Visual Analogue Scale Pain Score
VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change from baseline =scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis. n = the number of participants available for assessment at a given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Change From Baseline in Visual Analogue Scale Pain Score | Change from BL to Week 24, n = 204, 378 | -29.308 units on a scale |
| Tocilizumab | Mean Change From Baseline in Visual Analogue Scale Pain Score | Change from BL to Week 52, n = 183, 336 | -32.957 units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Visual Analogue Scale Pain Score | Change from BL to Week 24, n = 204, 378 | -23.647 units on a scale |
| TNF Inhibitor | Mean Change From Baseline in Visual Analogue Scale Pain Score | Change from BL to Week 52, n = 183, 336 | -23.155 units on a scale |
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor at Week 24: Analysis is based on an ANCOVA model with change from baseline to 6 months in participant's VAS score as dependent variable; therapy and treatment as fixed effects; participant's VAS score at baseline as covariates.p-value: 0.00995% CI: [-9.912, -1.411]ANCOVA
Comparison: Treatment Difference between Tocilizumab and TNF inhibitor at Week 52: Analysis is based on an ANCOVA model with change from baseline to 12 months in participant's VAS score as dependent variable; therapy and treatment as fixed effects; participant's VAS score at baseline as covariates.p-value: <0.00195% CI: [-14.245, -5.36]ANCOVA
Secondary
Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy
An infusion reaction was defined as an adverse event (AE) occurring during and within 24 hours after the infusion, which may include hypersensitivity reactions or anaphylactic reactions. Injection site reactions were included in the summaries for infusion reactions.
Time frame: Up to Week 52
Population: The safety population was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy | Participants with Non-Serious infusion reaction | 33 participants |
| Tocilizumab | Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy | Participants with Serious infusion reaction | 4 participants |
| TNF Inhibitor | Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy | Participants with Non-Serious infusion reaction | 75 participants |
| TNF Inhibitor | Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy | Participants with Serious infusion reaction | 3 participants |
Secondary
Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time frame: Up to Week 52
Population: The safety population was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | Participants with AE | 208 participants |
| Tocilizumab | Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | Participants with SAE | 22 participants |
| Tocilizumab | Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | Participants with non-serious AE | 196 participants |
| TNF Inhibitor | Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | Participants with AE | 449 participants |
| TNF Inhibitor | Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | Participants with SAE | 64 participants |
| TNF Inhibitor | Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | Participants with non-serious AE | 421 participants |
Secondary
Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study
Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events. Based on seriousness criteria, they were categorized as serious and non-serious adverse events of special interest.
Time frame: Up to Week 52
Population: The safety population was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study | Participants with Serious AESI | 13 participants |
| Tocilizumab | Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study | Participants with Non-Serious AESI | 22 participants |
| TNF Inhibitor | Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study | Participants with Serious AESI | 27 participants |
| TNF Inhibitor | Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study | Participants with Non-Serious AESI | 16 participants |
Secondary
Proportion of Participants Who Terminated Biologic Treatment
The proportion of participants who discontinued biologic treatment was compared between tocilizumab-treated and TNF inhibitor-treated participants.
Time frame: Up to Week 52
Population: The safety population was used for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Proportion of Participants Who Terminated Biologic Treatment | 14.9 Percentage of participants |
| TNF Inhibitor | Proportion of Participants Who Terminated Biologic Treatment | 27.4 Percentage of participants |
Secondary
Reasons for Treatment Discontinuation
The reasons for discontinuation of tocilizumab or TNF inhibitor is presented.
Time frame: Up to Week 52
Population: The safety population was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Reasons for Treatment Discontinuation | Adverse event | 24 participants |
| Tocilizumab | Reasons for Treatment Discontinuation | Lack of efficacy | 15 participants |
| Tocilizumab | Reasons for Treatment Discontinuation | Other | 24 participants |
| TNF Inhibitor | Reasons for Treatment Discontinuation | Adverse event | 87 participants |
| TNF Inhibitor | Reasons for Treatment Discontinuation | Lack of efficacy | 106 participants |
| TNF Inhibitor | Reasons for Treatment Discontinuation | Other | 23 participants |
Secondary
Shift From Baseline in Morning Stiffness
Shift tables presenting the number of participants in each bivariate category Week (W) 0 versus Week 24 and Week 52, with regards to morning stiffness at the different time points, was presented for each treatment arm. For participants who experienced joint stiffness while waking up in the morning, duration of morning stiffness was categorized as follows: Less than 30 minutes (min), Between 30 and 60 minutes, Between 60 and 120 minutes, Between 120 to 240 minutes, More than 240 minutes and the whole day. Baseline = BL
Time frame: Baseline, Week 24, Week 52
Population: The effectiveness analysis population was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, the whole day | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, 30-60 min | 9 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, < 30 min | 6 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, 60-120 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, < 30 min | 12 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, 120-240 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, 60-120 min | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, 30-60 min | 6 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, < 30 min | 17 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, 60-120 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, 30-60 min | 9 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, 60-120 min | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, 120-240 min | 3 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, < 30 min | 13 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, < 30 min | 20 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, 30-60 min | 8 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, 60-120 min | 4 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, < 30 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, 30-60 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, the whole day | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, 60-120 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, < 30 min | 14 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, 60-120 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, 30-60 min | 6 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, < 30 min | 22 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, 60-120 min | 5 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, 120-240 min | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, the whole day | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, 30-60 min | 17 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, < 30 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, 30-60 min | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, 30-60 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, < 30 min | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, 60-120 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, 60-120 min | 4 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, 120-240 min | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, 30-60 min | 3 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24 < 30 min | 19 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, 60-120 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, < 30 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, 30-60 min | 1 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, 60-120 min | 2 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, 120-240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, > 240 min | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, the whole day | 0 participants |
| Tocilizumab | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, 30-60 min | 2 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, 60-120 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, < 30 min | 19 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, 30-60 min | 8 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, 120-240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, > 240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 24, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24 < 30 min | 49 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, 30-60 min | 30 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, 60-120 min | 3 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, 120-240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, > 240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 24, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, < 30 min | 34 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, 30-60 min | 22 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, 60-120 min | 7 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, 120-240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, > 240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 24, the whole day | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, < 30 min | 10 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, 30-60 min | 9 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, 60-120 min | 8 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, 120-240 min | 4 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, > 240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 24, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, < 30 min | 7 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, 30-60 min | 2 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, 60-120 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, 120-240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, > 240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 24, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, < 30 min | 2 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, 30-60 min | 2 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, 60-120 min | 5 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, 120-240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, > 240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 24, the whole day | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, < 30 min | 13 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, 30-60 min | 4 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, 60-120 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, 120-240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, > 240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, < 30 min; W 52, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, < 30 min | 43 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, 30-60 min | 19 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, 60-120 min | 5 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, 120-240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, > 240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 30-60 min; W 52, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, < 30 min | 33 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, 30-60 min | 21 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, 60-120 min | 4 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, 120-240 min | 3 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, > 240 min | 2 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 60-120 min; W 52, the whole day | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, < 30 min | 9 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, 30-60 min | 6 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, 60-120 min | 8 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, 120-240 min | 3 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, > 240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, between 120-240 min; W 52, the whole day | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, < 30 min | 5 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, 30-60 min | 4 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, 60-120 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, 120-240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, > 240 min | 0 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, more than 240 min; W 52, the whole day | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, < 30 min | 3 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, 30-60 min | 2 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, 60-120 min | 2 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, 120-240 min | 1 participants |
| TNF Inhibitor | Shift From Baseline in Morning Stiffness | BL, the whole day; W 52, > 240 min | 0 participants |