Rheumatoid Arthritis
Conditions
Brief summary
This multicenter, prospective, observational study will assess the efficacy of MabThera/Rituxan (rituximab) and alternative TNF-inhibitors in patients with rheumatoid arthritis who are non-responders or intolerant to a single previous TNF-inhibitor. Data will be collected from each patient from the time of change in biologic therapy for 12 months.
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 * Patients with rheumatoid arthritis (RA) who have not responded or have been intolerant to a single TNF-inhibitor therapy * Initiated on treatment with MabThera/Rituxan or an alternative TNF-inhibitor therapy, in accordance with the relevant Summary of Product Characteristics
Exclusion criteria
* Patients whose second biologic therapy is given as part of a clinical trial studying RA treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month 6 | Baseline (Day of change in biologic therapy [<=Day 1]) and Month 6 | The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour \[mm/hr\]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in TJC at Months 6 and 12 | Baseline, Month 6, and Month 12 | The TJC is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). A total of 28 joints were assessed for tenderness. Decrease in score indicated an improvement in disease activity. |
| Least Squares Mean Change From Baseline in SJC at Months 6 and 12 | Baseline, Month 6, and Month 12 | The SJC is the most specific clinical method to quantify abnormalities in participants with RA. A total of 28 joints were assessed for swelling. Decrease in the score indicated improvement in disease activity. |
| Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12 | Baseline, Month 6, and Month 12 | C-reactive protein (CRP) is an inflammation marker. Normal range is from 0-10 milligram/Liter. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement in disease activity. |
| Least Squares Mean Change From Baseline in ESR at Months 6 and 12 | Baseline, Month 6, and Month 12 | The ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells sediment in a period of one hour. Normal range is 0-30 mm/hr. A reduction in the level of ESR is considered as an improvement in disease activity. |
| Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12 | Baseline, Month 6, and Month 12 | Physician global assessment of disease was measured on a 0 to 100 millimeter (mm) visual analog scale (VAS), with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease. |
| Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12 | Baseline, Month 6, and Month 12 | Patient Global Assessment of Disease was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease. |
| Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12 | Baseline, Month 6, and Month 12 | Participants were asked to assess their pain intensity (severity of pain) on a 100-millimeter (mm) VAS with the left edge (0 mm) defined as no pain and the right edge (100 mm) defined as severest pain. Higher scores indicate worsening of disease. |
| Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12 | Baseline, Month 6, and Month 12 | Health Assessment Questionnaire-Disability Index (HAQ-DI) is participant reported assessment of ability to perform tasks in 8 categories of daily living activities as dress/groom, arise, eat, walk, reach, grip, hygiene, and common activities over past week. Each item was scored on a 4-point scale from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible score range was 0-3, where 0 = least difficulty and 3 = extreme difficulty. |
| Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12 | Baseline (Day of change in biologic therapy [<=Day 1]) and Month 12 | The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour \[mm/hr\]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity. |
| Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy | Month 6 and Month 12 | Percentage of participants who remained on their second biologic therapy at 6 and 12 months after start of second biologic therapy were reported. |
| Reasons for Stopping the Second Biologic Therapy and Subsequent Therapy Choice | Up to 12 months | — |
| Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | Up to 12 Months | An Adverse event is defined as any unfavorable and unintended medical occurrence/sign (including an abnormal laboratory finding), symptom or disease in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above. |
| Number of Participants With Reasons for Discontinuation of the First TNFi Therapy | Day 1 (Study entry visit) | The reasons for discontinuation of first TNFi therapy included inefficacy, intolerance and other reasons. The other reasons included complete remission and participants' non-compliance. |
| Number of Participants With Previous TNFi Therapy | Day 1 (Study entry visit) | The previous TNFi therapy included adalimumab, etanercept, infliximab, and others (certolizumab, and golimumab). Number of participants with previous TNFi therapy history was reported. |
| Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Day 1 (Study entry visit) | The previous disease-modifying anti-rheumatic drugs therapy included auranofin, aurothioglucose, aurotioprol, azathioprine, chloroquine, ciclosporin, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, methotrexate sodium, minocycline, penicillamine, sodium aurothiomalate, sodium aurotiosulfate, sulfasalazine, and tiopronin. Number of participants with previous disease-modifying anti-rheumatic drugs therapy was reported. |
| Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Baseline | The factors included participant characteristics and the reasons that led to the selection of second biologic therapy following an insufficient response or intolerance to a single previous TNFi. The participant characteristics included participant's option for treatment and option for follow-up. The other reasons included RA disease (rheumatoid factor \[RF\] and cyclic citrullinated peptide \[CCP\] status), primary failure, and new treatment characteristics (rapidity of action, route of administration, frequency of administration, low infectious risk, and no lymphoma risk). Participants were included in more than one of these factors. |
| Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12 | Baseline, Month 6, and Month 12 | Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes. Participants with available data at the time of assessment were included in the analysis. |
Countries
Canada, Colombia, France, Germany, Greece, Italy, Mexico, Monaco, Norway, Portugal, Spain, United Kingdom
Participant flow
Recruitment details
This observational study was conducted in 11 countries from 02 June 2009 to 19 March 2012.
Pre-assignment details
Of 1239 enrolled participants, 9 had no information on second biologic treatment/reasons for discontinuing prior tumor necrosis factor inhibitor (TNFi), 1111 had one previous TNFi,119 had more than one previous TNFi. Of 1111 participants, 728 were considered for primary effectiveness analysis (405 in Rituximab arm and 323 in Alternative TNFi arm).
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy. | 405 |
| Alternative TNFi Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy. | 323 |
| Total | 728 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 18 | 11 |
| Overall Study | Adverse Event | 6 | 16 |
| Overall Study | Death | 7 | 4 |
| Overall Study | Infusion reaction event | 5 | 5 |
| Overall Study | Insufficient Therapeutic Response | 13 | 28 |
| Overall Study | Lost to Follow-up | 26 | 22 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Rituximab | Alternative TNFi | Total |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 12.61 | 54.7 years STANDARD_DEVIATION 13.26 | 55.7 years STANDARD_DEVIATION 12.93 |
| Gender Female | 310 Participants | 259 Participants | 569 Participants |
| Gender Male | 95 Participants | 64 Participants | 159 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 604 | 79 / 507 |
| serious Total, serious adverse events | 82 / 604 | 56 / 507 |
Outcome results
Primary
Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month 6
The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour \[mm/hr\]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.
Time frame: Baseline (Day of change in biologic therapy [<=Day 1]) and Month 6
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month 6 | -1.5 scores on a scale | Standard Error 0.22 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month 6 | -1.1 scores on a scale | Standard Error 0.23 |
p-value: 0.0068ANCOVA
Secondary
Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi
The factors included participant characteristics and the reasons that led to the selection of second biologic therapy following an insufficient response or intolerance to a single previous TNFi. The participant characteristics included participant's option for treatment and option for follow-up. The other reasons included RA disease (rheumatoid factor \[RF\] and cyclic citrullinated peptide \[CCP\] status), primary failure, and new treatment characteristics (rapidity of action, route of administration, frequency of administration, low infectious risk, and no lymphoma risk). Participants were included in more than one of these factors.
Time frame: Baseline
Population: Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy and reason for changing biologic therapy was known.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Participant's option for treatment | 272 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Participant's option for follow-up | 91 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | RA Disease (RF and CCP Status) | 344 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Primary failure | 256 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Rapidity of action | 82 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Route of administration | 123 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Frequency of administration | 303 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Low infectious risk | 172 participants |
| Rituximab | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | No lymphoma risk | 120 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Low infectious risk | 62 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Route of administration | 289 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Participant's option for follow-up | 89 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Participant's option for treatment | 278 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | RA Disease (RF and CCP Status) | 216 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Frequency of administration | 174 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Primary failure | 135 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | No lymphoma risk | 17 participants |
| Alternative TNFi | Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi | Rapidity of action | 203 participants |
Secondary
Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12
C-reactive protein (CRP) is an inflammation marker. Normal range is from 0-10 milligram/Liter. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement in disease activity.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12 | Month 6 (n= 278, 227) | -29.1 milligram/Liter | Standard Error 7.95 |
| Rituximab | Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12 | Month 12 (n=251, 199) | -11.6 milligram/Liter | Standard Error 8.47 |
| Alternative TNFi | Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12 | Month 6 (n= 278, 227) | -29.9 milligram/Liter | Standard Error 8.43 |
| Alternative TNFi | Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12 | Month 12 (n=251, 199) | -15.3 milligram/Liter | Standard Error 8.91 |
Comparison: Comparison of least squares mean change from Baseline in CRP at Month 6p-value: 0.8758ANCOVA
Comparison: Comparison of least squares mean change from Baseline in CRP at Month 12p-value: 0.4849ANCOVA
Secondary
Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12
The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour \[mm/hr\]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.
Time frame: Baseline (Day of change in biologic therapy [<=Day 1]) and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12 | -1.5 scores on a scale | Standard Error 0.27 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12 | -1.2 scores on a scale | Standard Error 0.29 |
p-value: 0.0588ANCOVA
Secondary
Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12
Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes. Participants with available data at the time of assessment were included in the analysis.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12 | Month 6 (n= 233, 180) | -19.0 minutes | Standard Error 25.38 |
| Rituximab | Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12 | Month 12 (n=206, 156) | -16.7 minutes | Standard Error 25.81 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12 | Month 6 (n= 233, 180) | -4.3 minutes | Standard Error 27.37 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12 | Month 12 (n=206, 156) | -1.4 minutes | Standard Error 28.19 |
Comparison: Comparison of least squares mean change from Baseline in duration of morning stiffness at month 6p-value: 0.3253ANCOVA
Comparison: Comparison of least squares mean change from Baseline in duration of morning stiffness at month 12p-value: 0.3535ANCOVA
Secondary
Least Squares Mean Change From Baseline in ESR at Months 6 and 12
The ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells sediment in a period of one hour. Normal range is 0-30 mm/hr. A reduction in the level of ESR is considered as an improvement in disease activity.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in ESR at Months 6 and 12 | Month 12 (n=297, 215) | -11.6 mm/hr | Standard Error 4.58 |
| Rituximab | Least Squares Mean Change From Baseline in ESR at Months 6 and 12 | Month 6 (n= 343, 250) | -13.2 mm/hr | Standard Error 3.91 |
| Alternative TNFi | Least Squares Mean Change From Baseline in ESR at Months 6 and 12 | Month 12 (n=297, 215) | -8.6 mm/hr | Standard Error 4.9 |
| Alternative TNFi | Least Squares Mean Change From Baseline in ESR at Months 6 and 12 | Month 6 (n= 343, 250) | -7.0 mm/hr | Standard Error 4.22 |
Comparison: Comparison of least squares mean change from Baseline in ESR at Month 6p-value: 0.0086ANCOVA
Comparison: Comparison of least squares mean change from Baseline in ESR at Month 12p-value: 0.2918ANCOVA
Secondary
Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12
Health Assessment Questionnaire-Disability Index (HAQ-DI) is participant reported assessment of ability to perform tasks in 8 categories of daily living activities as dress/groom, arise, eat, walk, reach, grip, hygiene, and common activities over past week. Each item was scored on a 4-point scale from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible score range was 0-3, where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12 | Month 6 (n= 164, 131) | -0.6 scores on a scale | Standard Error 0.18 |
| Rituximab | Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12 | Month 12 (n=142, 112) | -0.3 scores on a scale | Standard Error 0.2 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12 | Month 6 (n= 164, 131) | -0.5 scores on a scale | Standard Error 0.19 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12 | Month 12 (n=142, 112) | -0.2 scores on a scale | Standard Error 0.22 |
Comparison: Comparison of least squares mean change from Baseline in HAQ-DI at Month 6p-value: 0.337ANCOVA
Comparison: Comparison of least squares mean change from Baseline in HAQ-DI at Month 12p-value: 0.1515ANCOVA
Secondary
Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12
Participants were asked to assess their pain intensity (severity of pain) on a 100-millimeter (mm) VAS with the left edge (0 mm) defined as no pain and the right edge (100 mm) defined as severest pain. Higher scores indicate worsening of disease.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12 | Month 6 (n= 236, 197) | -15.7 mm | Standard Error 6.48 |
| Rituximab | Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12 | Month 12 (n=194, 171) | -19.0 mm | Standard Error 6.58 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12 | Month 6 (n= 236, 197) | -10.8 mm | Standard Error 7.02 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12 | Month 12 (n=194, 171) | -10.0 mm | Standard Error 7.1 |
Comparison: Comparison of least squares mean change from Baseline in Participant's Visual Analogue Scale Pain Score at Months 6p-value: 0.2026ANCOVA
Comparison: Comparison of least squares mean change from Baseline in Participant's Visual Analogue Scale Pain Score at Months 12p-value: 0.0295ANCOVA
Secondary
Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12
Patient Global Assessment of Disease was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12 | Month 6 (n= 288, 219) | -17.0 mm | Standard Error 5.48 |
| Rituximab | Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12 | Month 12 (n= 242, 189) | -19.7 mm | Standard Error 5.85 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12 | Month 6 (n= 288, 219) | -10.2 mm | Standard Error 5.77 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12 | Month 12 (n= 242, 189) | -17.1 mm | Standard Error 6.24 |
Comparison: Comparison of least squares mean change from Baseline in Patient Global Assessment of Disease at Month 6p-value: 0.0443ANCOVA
Comparison: Comparison of least squares mean change from Baseline in Patient Global Assessment of Disease at Month 12p-value: 0.4802ANCOVA
Secondary
Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12
Physician global assessment of disease was measured on a 0 to 100 millimeter (mm) visual analog scale (VAS), with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12 | Month 6 (n= 203, 169) | -21.0 mm | Standard Error 6.13 |
| Rituximab | Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12 | Month 12 (n= 169, 144) | -21.8 mm | Standard Error 6.69 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12 | Month 6 (n= 203, 169) | -14.8 mm | Standard Error 6.65 |
| Alternative TNFi | Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12 | Month 12 (n= 169, 144) | -14.3 mm | Standard Error 7.3 |
Comparison: Comparison of least squares mean change from Baseline in Physician Global Assessment of Disease at Month 6p-value: 0.0764ANCOVA
Comparison: Comparison of least squares mean change from Baseline in Physician Global Assessment of Disease at Month 12p-value: 0.0587ANCOVA
Secondary
Least Squares Mean Change From Baseline in SJC at Months 6 and 12
The SJC is the most specific clinical method to quantify abnormalities in participants with RA. A total of 28 joints were assessed for swelling. Decrease in the score indicated improvement in disease activity.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in SJC at Months 6 and 12 | Month 6 (n= 339, 256) | -3.3 swollen joints | Standard Error 0.93 |
| Rituximab | Least Squares Mean Change From Baseline in SJC at Months 6 and 12 | Month 12 (n= 283, 215) | -2.7 swollen joints | Standard Error 0.99 |
| Alternative TNFi | Least Squares Mean Change From Baseline in SJC at Months 6 and 12 | Month 6 (n= 339, 256) | -2.8 swollen joints | Standard Error 0.97 |
| Alternative TNFi | Least Squares Mean Change From Baseline in SJC at Months 6 and 12 | Month 12 (n= 283, 215) | -2.4 swollen joints | Standard Error 1.04 |
Comparison: Comparison of least squares mean change from Baseline in SJC at Month 6p-value: 0.4168ANCOVA
Comparison: Comparison of least squares mean change from Baseline in SJC at Month 12p-value: 0.5867ANCOVA
Secondary
Least Squares Mean Change From Baseline in TJC at Months 6 and 12
The TJC is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). A total of 28 joints were assessed for tenderness. Decrease in score indicated an improvement in disease activity.
Time frame: Baseline, Month 6, and Month 12
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as 'n'.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Least Squares Mean Change From Baseline in TJC at Months 6 and 12 | Month 6 (n= 338, 255) | -5.7 tender joints | Standard Error 1.2 |
| Rituximab | Least Squares Mean Change From Baseline in TJC at Months 6 and 12 | Month 12 (n= 281, 216) | -4.7 tender joints | Standard Error 1.29 |
| Alternative TNFi | Least Squares Mean Change From Baseline in TJC at Months 6 and 12 | Month 6 (n= 338, 255) | -4.5 tender joints | Standard Error 1.24 |
| Alternative TNFi | Least Squares Mean Change From Baseline in TJC at Months 6 and 12 | Month 12 (n= 281, 216) | -3.7 tender joints | Standard Error 1.36 |
Comparison: Comparison of least squares mean change from Baseline in TJC at Month 6p-value: 0.1126ANCOVA
Comparison: Comparison of least squares mean change from Baseline in TJC at Month 12p-value: 0.2342ANCOVA
Secondary
Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death
An Adverse event is defined as any unfavorable and unintended medical occurrence/sign (including an abnormal laboratory finding), symptom or disease in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Time frame: Up to 12 Months
Population: Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy and reason for changing biologic therapy was known.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | Any AE | 291 participants |
| Rituximab | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | Any SAE | 82 participants |
| Rituximab | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | AE leading to withdrawal | 17 participants |
| Rituximab | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | Death | 7 participants |
| Alternative TNFi | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | Death | 4 participants |
| Alternative TNFi | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | Any AE | 241 participants |
| Alternative TNFi | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | AE leading to withdrawal | 39 participants |
| Alternative TNFi | Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death | Any SAE | 56 participants |
Secondary
Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy
The previous disease-modifying anti-rheumatic drugs therapy included auranofin, aurothioglucose, aurotioprol, azathioprine, chloroquine, ciclosporin, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, methotrexate sodium, minocycline, penicillamine, sodium aurothiomalate, sodium aurotiosulfate, sulfasalazine, and tiopronin. Number of participants with previous disease-modifying anti-rheumatic drugs therapy was reported.
Time frame: Day 1 (Study entry visit)
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Tiopronin | 0 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Chloroquine | 27 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Sodium aurotiosulfate | 0 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Ciclosporin | 25 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Auranofin | 5 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Gold | 27 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Sodium aurothiomalate | 17 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Hydroxychloroquine | 96 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Aurothioglucose | 0 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Infliximab | 1 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Sulfasalazine | 107 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Leflunomide | 144 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Aurotioprol | 4 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Methotrexate | 199 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Penicillamine | 7 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Methotrexate sodium | 3 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Azathioprine | 20 participants |
| Rituximab | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Minocycline | 0 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Azathioprine | 9 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Penicillamine | 5 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Sodium aurothiomalate | 4 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Sodium aurotiosulfate | 1 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Sulfasalazine | 86 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Tiopronin | 1 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Auranofin | 6 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Aurothioglucose | 1 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Aurotioprol | 4 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Minocycline | 3 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Chloroquine | 11 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Ciclosporin | 27 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Gold | 20 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Hydroxychloroquine | 99 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Infliximab | 0 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Leflunomide | 126 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Methotrexate | 180 participants |
| Alternative TNFi | Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy | Methotrexate sodium | 1 participants |
Secondary
Number of Participants With Previous TNFi Therapy
The previous TNFi therapy included adalimumab, etanercept, infliximab, and others (certolizumab, and golimumab). Number of participants with previous TNFi therapy history was reported.
Time frame: Day 1 (Study entry visit)
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points are denoted as 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Previous TNFi Therapy | Golimumab (Simponi) | 0 participants |
| Rituximab | Number of Participants With Previous TNFi Therapy | Adalimumab (Humira) | 131 participants |
| Rituximab | Number of Participants With Previous TNFi Therapy | Etanercept (Enbrel) | 176 participants |
| Rituximab | Number of Participants With Previous TNFi Therapy | Infliximab (Remicade) | 95 participants |
| Rituximab | Number of Participants With Previous TNFi Therapy | Certolizumab pegol (Cimzia) | 3 participants |
| Alternative TNFi | Number of Participants With Previous TNFi Therapy | Certolizumab pegol (Cimzia) | 0 participants |
| Alternative TNFi | Number of Participants With Previous TNFi Therapy | Infliximab (Remicade) | 42 participants |
| Alternative TNFi | Number of Participants With Previous TNFi Therapy | Adalimumab (Humira) | 116 participants |
| Alternative TNFi | Number of Participants With Previous TNFi Therapy | Golimumab (Simponi) | 3 participants |
| Alternative TNFi | Number of Participants With Previous TNFi Therapy | Etanercept (Enbrel) | 162 participants |
Secondary
Number of Participants With Reasons for Discontinuation of the First TNFi Therapy
The reasons for discontinuation of first TNFi therapy included inefficacy, intolerance and other reasons. The other reasons included complete remission and participants' non-compliance.
Time frame: Day 1 (Study entry visit)
Population: The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Reasons for Discontinuation of the First TNFi Therapy | Other reasons | 5 participants |
| Rituximab | Number of Participants With Reasons for Discontinuation of the First TNFi Therapy | Inefficacy | 311 participants |
| Rituximab | Number of Participants With Reasons for Discontinuation of the First TNFi Therapy | Intolerance | 89 participants |
| Alternative TNFi | Number of Participants With Reasons for Discontinuation of the First TNFi Therapy | Inefficacy | 236 participants |
| Alternative TNFi | Number of Participants With Reasons for Discontinuation of the First TNFi Therapy | Intolerance | 79 participants |
| Alternative TNFi | Number of Participants With Reasons for Discontinuation of the First TNFi Therapy | Other reasons | 8 participants |
Secondary
Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy
Percentage of participants who remained on their second biologic therapy at 6 and 12 months after start of second biologic therapy were reported.
Time frame: Month 6 and Month 12
Population: Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy (i.e,Treatment Group) and reason for changing biologic therapy was known.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy | NA Percentage of participants |
| Alternative TNFi | Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy | NA Percentage of participants |
Secondary
Reasons for Stopping the Second Biologic Therapy and Subsequent Therapy Choice
Time frame: Up to 12 months
Population: Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy (ie,Treatment Group) and reason for changing biologic therapy was known.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Reasons for Stopping the Second Biologic Therapy and Subsequent Therapy Choice | NA Number of participants |
| Alternative TNFi | Reasons for Stopping the Second Biologic Therapy and Subsequent Therapy Choice | NA Number of participants |