Rheumatoid Arthritis
Conditions
Brief summary
This single arm study will assess the safety of MabThera plus methotrexate in patients with rheumatoid arthritis who have had a lack of response to 1-5 DMARDs or biological agents. Patients will receive MabThera (1g i.v.) on days 1 and 15, concomitantly with methotrexate \>=15mg p.o./week. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGMethotrexate
\>=15 mg po/week
DRUGrituximab [MabThera/Rituxan]
1g iv on days 1 and 15
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * rheumatoid arthritis \>=6 months; * lack of response to 1-5 DMARDs or biological agents; * rheumatoid factor positive.
Exclusion criteria
* other chronic inflammatory articular disease or systemic rheumatic disease; * joint or bone surgery during 8 weeks prior to randomization; * previous treatment with any cell-depleting therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death | Up to Week 48 | An Adverse event (AE) was considered any unfavorable medical event in a participant of clinical research who received the study drug and that not necessarily had a causal relationship with this treatment. An AE could, therefore, being any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A serious adverse event (SAE) is any experience that suggested a significant risk, contraindication, caution, and at any dose fulfills at least one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment. |
| Number of Participants With AEs According to Degree of Intensity | Up to Week 48 | An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. The Intensity of AEs was classified as Grade 1, Grade 2, Grade 3 and Grade 4. Grade 1: Discomfort was noticed, but the normal daily activity was not interrupted. Grade 2: Discomfort was enough to reduce the normal daily activity. Grade 3: There was disability for work or develop normal daily activities. Grade 4: It represented an immediate threat to life (these events were reported as SAEs). |
| Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs | Up to Week 48 | An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A SAE is any experience that suggested a significant risk, contraindication, caution, and at any dose, fulfills, at least, one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment. Relationship between AEs and medication under investigation was evaluated through the classification Yes and No. A relationship classified as Yes implied a significant causal relationship with the medication under investigation which was evaluated based on enough evidences, facts or arguments. |
| Number of Participants With AEs of Special Interest During the Study | Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) | Adverse event of special interest during the study treatment and follow up period included infections. The participants with AEs of special interest were reported at Screening, End of treatment (EOT), and End of Follow-up (EOFU) visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets) | Screening (Days -28 to 0) and EOT (Week 24) | The mean leucocytes and platelets concentration for each participant was estimated at Screening, at EOT visit. |
| Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose) | Screening (Days -28 to 0) and EOT (Week 24) | The mean albumin and glucose concentration for each participant was estimated at Screening and at EOT visit. |
| Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Screening (Days -28 to 0) and EOT (Week 24) | The mean concentration of cholesterol, uric acid, urea, creatinine, calcium, total bilirubin and serum total proteins (STP) for each participant was estimated at Screening and at EOT visit. |
| Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Screening (Days -28 to 0) and EOT (Week 24) | The mean concentration of potassium, chlorine, sodium and phosphorus for each participant was estimated at Screening and at EOT. |
| Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | Screening (Days -28 to 0) and EOT (Week 24) | The mean aspartate transaminase (AST) and alanine transaminase (ALT), Alkaline phosphatase (AP), and Lactic dehydrogenase (LDH) concentration for each participant was estimated at Screening and at EOT visit. |
| Mean Duration of Morning Joint Stiffness | Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48) | The efficacy of rituximab was assessed by evaluating mean duration of morning joint stiffness. |
| Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration) | Screening (Days -28 to 0) and EOT (Week 24) | The values of hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) for each participant were estimated at Screening and at EOT visit. |
| Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | Week 1, Week 12, and Week 24 | American College of Rheumatology (ACR) criteria improvement consisting of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) reduction in tender joints and swollen joints, as well as for three of the additional five ACR core set variables: patient's assessment of pain using a Visual Analog Scale (VAS) with left end of the line 0=no pain to right end of the line 100=unbearable pain); patient's global assessment of disease activity and physician's global assessment of disease activity using a VAS (0=no disease activity to 100=maximum disease activity); health assessment questionnaire (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant; C-reactive protein and globular sedimentation velocity. |
| Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index) | Screening (Days -28 to 0), Week 1, Week 12, and Week 24 | Health Assessment Questionnaire - Disease Index (HAQ-DI) indicates how the disease affected participant's activities of daily life. It consisted of 20 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale, 0=without any difficulty to 3=unable to do. Sum of scores was divided by number of domains with a score for a total possible score of 0 (best/no difficulties to perform activities) to 3 (worst/ unable to perform activities at all). |
| Mean Values of C Reactive Protein | Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48) | C Reactive Protein (CRP) is a component of ACR. CRP is a marker of inflammation. |
| Mean Values of Globular Sedimentation Velocity | Screening ((Days -28 to 0), Week 1, Week 12, and Week 24 | Globular sedimentation velocity is a component of ACR. |
| Mean Values of Pain and Activity Based on Visual Analogue Scale | Screening ((Days -28 to 0), Week 1, Week 12, and Week 24 | Pain assessment was assessed by using a VAS (0=no pain to 100=unbearable pain). Disease activity was also evaluated by participants and investigators by using a VAS (0=no disease activity to 100=maximum disease activity). |
| Mean Value of Inflamed Joints | Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) | The efficacy of rituximab was assessed by evaluating inflamed joints. |
| Mean Value of Painful Joints | Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) | The efficacy of rituximab was assessed by evaluating painful joints. |
| Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Screening (Days -28 to 0) and EOT (Week 24) | The hematology parameters (hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, and basophils) for each participant were estimated at Screening and at EOT. |
| Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume) | Screening (Days -28 to 0) and EOT (Week 24) | Mean corpuscular volume (MCV) is the average volume of red cells. The mean MCV concentration for each participant was estimated at Screening and EOT. |
| Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes) | Screening (Days -28 to 0) and EOT (Week 24) | The mean erythrocyte concentration for each participant was estimated at Screening and at EOT. |
Countries
Argentina, Brazil, Chile, Colombia, Ecuador, El Salvador, Mexico, Peru, Uruguay, Venezuela
Participant flow
Recruitment details
A total of 246 participants were enrolled in study conducted from 20 February 2006 to 05 December 2008 across 56 study centers in 10 Latin American countries.
Pre-assignment details
Out of 246 participants, fourteen did not receive study drug and were not included in analysis population.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Eligible participants receiving Rituximab 1 g/dose IV on Day 1 and Day 15 followed by previous pre-medication (methylprednisolone 100 mg IV, antihistamine and antipyretic) and concomitant treatment of Methotrexate at least 15 mg PO weekly were observed during the study period of 24 weeks. After treatment completion, participants were followed-up for safety up to 24 weeks. | 232 |
| Total | 232 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Treatment failure | 25 |
| Overall Study | Withdrawal Informed Consent | 6 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 207 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 189 / 232 |
| serious Total, serious adverse events | 12 / 232 |
Outcome results
Primary
Number of Participants With AEs According to Degree of Intensity
An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. The Intensity of AEs was classified as Grade 1, Grade 2, Grade 3 and Grade 4. Grade 1: Discomfort was noticed, but the normal daily activity was not interrupted. Grade 2: Discomfort was enough to reduce the normal daily activity. Grade 3: There was disability for work or develop normal daily activities. Grade 4: It represented an immediate threat to life (these events were reported as SAEs).
Time frame: Up to Week 48
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With AEs According to Degree of Intensity | Grade 1 AEs | 170 participants |
| Rituximab | Number of Participants With AEs According to Degree of Intensity | Grade 2 AEs | 102 participants |
| Rituximab | Number of Participants With AEs According to Degree of Intensity | Grade 3 AEs | 30 participants |
| Rituximab | Number of Participants With AEs According to Degree of Intensity | Grade 4 AEs | 12 participants |
Primary
Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs
An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A SAE is any experience that suggested a significant risk, contraindication, caution, and at any dose, fulfills, at least, one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment. Relationship between AEs and medication under investigation was evaluated through the classification Yes and No. A relationship classified as Yes implied a significant causal relationship with the medication under investigation which was evaluated based on enough evidences, facts or arguments.
Time frame: Up to Week 48
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs | Any drug related AE | 97 participants |
| Rituximab | Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs | Any drug related SAE | 0 participants |
| Rituximab | Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs | Any AE leading to discontinuation | 2 participants |
Primary
Number of Participants With AEs of Special Interest During the Study
Adverse event of special interest during the study treatment and follow up period included infections. The participants with AEs of special interest were reported at Screening, End of treatment (EOT), and End of Follow-up (EOFU) visit.
Time frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With AEs of Special Interest During the Study | Screening | 5 participants |
| Rituximab | Number of Participants With AEs of Special Interest During the Study | EOT | 12 participants |
| Rituximab | Number of Participants With AEs of Special Interest During the Study | EOFU | 12 participants |
Primary
Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death
An Adverse event (AE) was considered any unfavorable medical event in a participant of clinical research who received the study drug and that not necessarily had a causal relationship with this treatment. An AE could, therefore, being any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A serious adverse event (SAE) is any experience that suggested a significant risk, contraindication, caution, and at any dose fulfills at least one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment.
Time frame: Up to Week 48
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death | Any AE | 189 participants |
| Rituximab | Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death | Any SAE | 12 participants |
| Rituximab | Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death | Death | 0 participants |
Secondary
Mean Duration of Morning Joint Stiffness
The efficacy of rituximab was assessed by evaluating mean duration of morning joint stiffness.
Time frame: Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Duration of Morning Joint Stiffness | Screening | 120.1 Minutes | Standard Deviation 96.3 |
| Rituximab | Mean Duration of Morning Joint Stiffness | EOT | 16.0 Minutes | Standard Deviation 36.5 |
| Rituximab | Mean Duration of Morning Joint Stiffness | EOFU | 19.9 Minutes | Standard Deviation 42.4 |
Secondary
Mean Value of Inflamed Joints
The efficacy of rituximab was assessed by evaluating inflamed joints.
Time frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Value of Inflamed Joints | Inflamed joints, Screening | 17.5 number of inflamed joints | Standard Deviation 8.6 |
| Rituximab | Mean Value of Inflamed Joints | Inflamed joints, EOT | 3.8 number of inflamed joints | Standard Deviation 4.9 |
| Rituximab | Mean Value of Inflamed Joints | Inflamed joints, EOFU | 4.4 number of inflamed joints | Standard Deviation 5.7 |
Secondary
Mean Value of Painful Joints
The efficacy of rituximab was assessed by evaluating painful joints.
Time frame: Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Value of Painful Joints | Painful joints, EOT | 3.8 number of painful joints | Standard Deviation 4.9 |
| Rituximab | Mean Value of Painful Joints | Painful joints, EOFU | 4.4 number of painful joints | Standard Deviation 5.7 |
| Rituximab | Mean Value of Painful Joints | Painful joints, Screening | 17.5 number of painful joints | Standard Deviation 8.6 |
Secondary
Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index)
Health Assessment Questionnaire - Disease Index (HAQ-DI) indicates how the disease affected participant's activities of daily life. It consisted of 20 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale, 0=without any difficulty to 3=unable to do. Sum of scores was divided by number of domains with a score for a total possible score of 0 (best/no difficulties to perform activities) to 3 (worst/ unable to perform activities at all).
Time frame: Screening (Days -28 to 0), Week 1, Week 12, and Week 24
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index) | Screening; n = 106 | 2.6 Scores on scale | Standard Deviation 1.3 |
| Rituximab | Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index) | Week 1; n = 114 | 2.5 Scores on scale | Standard Deviation 1.4 |
| Rituximab | Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index) | Week 12; n = 107 | 1.25 Scores on scale | Standard Deviation 1 |
| Rituximab | Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index) | Week 24; n = 105 | 1.0 Scores on scale | Standard Deviation 1 |
Secondary
Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit
The mean aspartate transaminase (AST) and alanine transaminase (ALT), Alkaline phosphatase (AP), and Lactic dehydrogenase (LDH) concentration for each participant was estimated at Screening and at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | AST, Screening | 21.6 International units/liter | Standard Deviation 9.7 |
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | AST, EOT | 22.0 International units/liter | Standard Deviation 9.5 |
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | ALT, Screening | 24.1 International units/liter | Standard Deviation 14.9 |
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | ALT, EOT | 25.9 International units/liter | Standard Deviation 14.9 |
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | AP, Screening | 137.7 International units/liter | Standard Deviation 71.6 |
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | AP, EOT | 138.2 International units/liter | Standard Deviation 81.7 |
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | LDH, Screening | 311.0 International units/liter | Standard Deviation 149.1 |
| Rituximab | Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit | LDH, EOT | 300.5 International units/liter | Standard Deviation 125.4 |
Secondary
Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose)
The mean albumin and glucose concentration for each participant was estimated at Screening and at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose) | Albumin, Screening | 3.9 g/dL | Standard Deviation 0.5 |
| Rituximab | Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose) | Albumin, EOT | 4.1 g/dL | Standard Deviation 0.4 |
| Rituximab | Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose) | Glucose, Screening | 86.1 g/dL | Standard Deviation 12.3 |
| Rituximab | Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose) | Glucose, EOT | 88.1 g/dL | Standard Deviation 26.5 |
Secondary
Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit.
The mean concentration of cholesterol, uric acid, urea, creatinine, calcium, total bilirubin and serum total proteins (STP) for each participant was estimated at Screening and at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Cholesterol, Screening | 187.9 mg/dL | Standard Deviation 42.2 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Cholesterol, EOT | 196.6 mg/dL | Standard Deviation 42.7 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Uric acid, Screening | 4.0 mg/dL | Standard Deviation 1.2 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Uric acid, EOT | 4.0 mg/dL | Standard Deviation 1.1 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Urea, Screening | 29.3 mg/dL | Standard Deviation 10 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Urea, EOT | 30.2 mg/dL | Standard Deviation 11 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Creatinine, Screening | 0.7 mg/dL | Standard Deviation 0.2 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Creatinine, EOT | 0.7 mg/dL | Standard Deviation 0.2 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Calcium, Screening | 9.0 mg/dL | Standard Deviation 1.3 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Calcium, EOT | 9.0 mg/dL | Standard Deviation 1 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Total Bilirubin, Screening | 0.7 mg/dL | Standard Deviation 1.1 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | Total Bilirubin, EOT | 0.7 mg/dL | Standard Deviation 1.1 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | STP, Screening | 7.3 mg/dL | Standard Deviation 0.6 |
| Rituximab | Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. | STP, EOT | 7.1 mg/dL | Standard Deviation 0.6 |
Secondary
Mean Values of C Reactive Protein
C Reactive Protein (CRP) is a component of ACR. CRP is a marker of inflammation.
Time frame: Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48)
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of C Reactive Protein | Week 24 | 15.3 milligrams per liter | Standard Deviation 45.2 |
| Rituximab | Mean Values of C Reactive Protein | Screening | 28.0 milligrams per liter | Standard Deviation 45.3 |
| Rituximab | Mean Values of C Reactive Protein | Week 1 | 27.6 milligrams per liter | Standard Deviation 56.1 |
| Rituximab | Mean Values of C Reactive Protein | Week 12 | 13.6 milligrams per liter | Standard Deviation 25 |
Secondary
Mean Values of Globular Sedimentation Velocity
Globular sedimentation velocity is a component of ACR.
Time frame: Screening ((Days -28 to 0), Week 1, Week 12, and Week 24
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Globular Sedimentation Velocity | Screening | 43.7 millimeters per hour | Standard Deviation 22.8 |
| Rituximab | Mean Values of Globular Sedimentation Velocity | Week 1 | 41.1 millimeters per hour | Standard Deviation 23 |
| Rituximab | Mean Values of Globular Sedimentation Velocity | Week 12 | 26.8 millimeters per hour | Standard Deviation 17.8 |
| Rituximab | Mean Values of Globular Sedimentation Velocity | Week 24 | 24.6 millimeters per hour | Standard Deviation 19 |
Secondary
Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes)
The mean erythrocyte concentration for each participant was estimated at Screening and at EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes) | Erythrocytes, Screening | 4.5 10^12 cells/liter | Standard Deviation 1.2 |
| Rituximab | Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes) | Erythrocytes, EOT | 4.4 10^12 cells/liter | Standard Deviation 0.5 |
Secondary
Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume)
Mean corpuscular volume (MCV) is the average volume of red cells. The mean MCV concentration for each participant was estimated at Screening and EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The analysis was performed on safety population. Eligible participants who received one treatment dose of Rituximab, have completed the follow-up period, Visit 11, and end of follow-up period in safety conditions and also who had been withdrawn or not from the study were included in the safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume) | MCV, Screening | 85.8 femtoliters | Standard Deviation 8.5 |
| Rituximab | Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume) | MCV, EOT | 87.7 femtoliters | Standard Deviation 7 |
Secondary
Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils)
The hematology parameters (hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, and basophils) for each participant were estimated at Screening and at EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Hematocrit, Screening | 37.8 percentage of cells | Standard Deviation 4.2 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Hematocrit, EOT | 38.9 percentage of cells | Standard Deviation 4.3 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Neutrophils, Screening | 67.8 percentage of cells | Standard Deviation 9.4 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Neutrophils, EOT | 65.1 percentage of cells | Standard Deviation 9.9 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Lymphocytes, Screening | 24.0 percentage of cells | Standard Deviation 7.7 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Lymphocytes, EOT | 25.6 percentage of cells | Standard Deviation 8.7 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Monocytes, Screening | 4.3 percentage of cells | Standard Deviation 3.1 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Monocytes, EOT | 5.4 percentage of cells | Standard Deviation 3.6 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Eosinophils, Screening | 1.9 percentage of cells | Standard Deviation 2 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Eosinophils, EOT | 2.5 percentage of cells | Standard Deviation 2 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Basophils, Screening | 0.2 percentage of cells | Standard Deviation 0.3 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | Basophils, EOT | 0.3 percentage of cells | Standard Deviation 0.4 |
Secondary
Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration)
The values of hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) for each participant were estimated at Screening and at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration) | Hb, Screening | 12.4 g/deciliter (dL) | Standard Deviation 1.9 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration) | Hb, EOT | 12.8 g/deciliter (dL) | Standard Deviation 1.6 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration) | MCHC, Screening | 30.0 g/deciliter (dL) | Standard Deviation 3.6 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration) | MCHC, EOT | 30.9 g/deciliter (dL) | Standard Deviation 2.7 |
Secondary
Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets)
The mean leucocytes and platelets concentration for each participant was estimated at Screening, at EOT visit.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets) | Leucocytes, Screening | 8.6 10^9 cells/liter | Standard Deviation 2.6 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets) | Leucocytes, EOT | 7.7 10^9 cells/liter | Standard Deviation 2.3 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets) | Platelets, Screening | 351.6 10^9 cells/liter | Standard Deviation 112.5 |
| Rituximab | Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets) | Platelets, EOT | 310.6 10^9 cells/liter | Standard Deviation 97.1 |
Secondary
Mean Values of Pain and Activity Based on Visual Analogue Scale
Pain assessment was assessed by using a VAS (0=no pain to 100=unbearable pain). Disease activity was also evaluated by participants and investigators by using a VAS (0=no disease activity to 100=maximum disease activity).
Time frame: Screening ((Days -28 to 0), Week 1, Week 12, and Week 24
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Pain, Screening | 6.9 Scores on scale | Standard Deviation 1.9 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Pain, Week 1 | 6.9 Scores on scale | Standard Deviation 1.9 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Pain, Week 12 | 3.6 Scores on scale | Standard Deviation 2.4 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Pain, Week 24 | 3.0 Scores on scale | Standard Deviation 2.2 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (participant), Screening | 6.6 Scores on scale | Standard Deviation 2.3 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (participant), Week 1 | 5.9 Scores on scale | Standard Deviation 2.5 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (participant), Week 12 | 4.7 Scores on scale | Standard Deviation 2.8 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (participant), Week 24 | 3.9 Scores on scale | Standard Deviation 2.7 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (investigator), Screening | 6.4 Scores on scale | Standard Deviation 2 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (investigator), Week 1 | 6.3 Scores on scale | Standard Deviation 2.1 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (investigator), Week 12 | 3.9 Scores on scale | Standard Deviation 3.9 |
| Rituximab | Mean Values of Pain and Activity Based on Visual Analogue Scale | Activity (investigator), Week 24 | 3.0 Scores on scale | Standard Deviation 2.5 |
Secondary
Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit
The mean concentration of potassium, chlorine, sodium and phosphorus for each participant was estimated at Screening and at EOT.
Time frame: Screening (Days -28 to 0) and EOT (Week 24)
Population: The safety population included all eligible participants who received one treatment dose of rituximab and have completed the follow up period (Week 48) regardless of whether withdrawn or not from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Sodium, Screening | 140.1 millimoles per liter | Standard Deviation 3.3 |
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Sodium, EOT | 140.4 millimoles per liter | Standard Deviation 3.3 |
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Potassium, Screening | 4.2 millimoles per liter | Standard Deviation 0.4 |
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Potassium, EOT | 4.2 millimoles per liter | Standard Deviation 0.4 |
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Chlorine, Screening | 103.1 millimoles per liter | Standard Deviation 4.2 |
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Chlorine, EOT | 103.3 millimoles per liter | Standard Deviation 4.2 |
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Phosphorus, Screening | 3.7 millimoles per liter | Standard Deviation 0.6 |
| Rituximab | Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit | Phosphorus, EOT | 3.8 millimoles per liter | Standard Deviation 0.7 |
Secondary
Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria
American College of Rheumatology (ACR) criteria improvement consisting of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) reduction in tender joints and swollen joints, as well as for three of the additional five ACR core set variables: patient's assessment of pain using a Visual Analog Scale (VAS) with left end of the line 0=no pain to right end of the line 100=unbearable pain); patient's global assessment of disease activity and physician's global assessment of disease activity using a VAS (0=no disease activity to 100=maximum disease activity); health assessment questionnaire (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant; C-reactive protein and globular sedimentation velocity.
Time frame: Week 1, Week 12, and Week 24
Population: All eligible participants who received one treatment dose of rituximab were considered for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 20, Week 1 | 1 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 20, Week 12 | 84 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 20, Week 24 | 88 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 50, Week 1 | 0 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 50, Week 12 | 50 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 50, Week 24 | 62 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 70, Week 1 | 0 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 70, Week 12 | 33 participants |
| Rituximab | Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria | ACR 70, Week 24 | 42 participants |