Rheumatoid Arthritis
Conditions
Brief summary
This multicenter prospective observational study will evaluate the quality of life in participants with rheumatoid arthritis (RA) who are initiated with rituximab (MabThera/Rituxan). Participants will be followed for 6 months from initiation of treatment.
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 participants of both genders who are 18 years or older * Diagnosis of RA for at least 6 months according to the criteria of the American College of Rheumatology (ACR) of 1987 for the RA classification * Participants with medically prescribed or being administered with unique rituximab infusion in the least 3 days, according to the approved label * Ability to meet the program's requirements and to voluntarily sign the Informed Consent Term.
Exclusion criteria
* Participants who have received any investigational medication within less than or equal to (\<=) 1 year before the first dose of the currently indicated treatment * Participants with an active infection * Participants with conditions that may interfere in the ability to understand the requests of data collection and to obey to the study's requirements * Functional Class IV defined based on the ACR functionality criteria for RA * Participants who can not or who do not want, for any reason, to answer the questionnaires.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Improvement of at Least 0.22 Units in Health Assessment Questionnaire (HAQ) at Week 24 | Week 24 | The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. The proportion of participants achieving a clinically important reduction of \>= 0.22 point in HAQ (disease-specific questionnaire) at Week 24 was evaluated. HAQ was assessed using the set of observed cases (OC) at each assessment time. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement. |
| Mean Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 24 | Baseline and Week 24 | SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline, Week 12, Week 24 | Erythrocyte Sedimentation Rate is an acute phase reactant and a measure of inflammation. |
| Mean Change From Baseline in C-reactive Protein (CRP). | Baseline, Week 12, Week 24 | CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as Rheumatoid Arthritis. |
| Mean Change From Baseline in Swollen Joint Count (SJC) | Baseline, Week 12, Week 24 | A swollen joint count is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). It reflects the amount of inflamed synovial tissue. |
| Mean Change From Baseline in Tender Joint Count (TJC) | Baseline, Week 12, Week 24 | A tender joint count is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). It is associated more with the level of pain. |
| Mean Change From Baseline in Patient Global Assessment (100 mm VAS) | Baseline, Week 12, Week 24 | The Physician's Global Assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity).Change from Baseline = scores at observation minus score at Baseline. An increase in score from Baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. |
| Mean Change From Baseline in Disease Activity Score 28 Joints (DAS28) Score | Baseline, Week 12, Week 24 | DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to disease activity. A DAS28 score of less than or equal to (=\<) 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity. |
| Change in Pain Scale (100-mm VAS) From Screening to Weeks 12 and 24 | Baseline, Week 12, Week 24 | Visual Analogue Scale (VAS) is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change from Screening=scores at observation minus score at Screening. An increase in score from Screening represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. The change in pain scale was analyzed for the set of observed cases (OC) at each assessment time. |
| Change in SF-36 Physical and Mental Component Scores From Screening to Week 12 | Baseline, Week 12 | SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time. |
| Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Baseline, Week 12, Week 24 | SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time. |
| Percentage of Participants Achieving a Clinically Important Reduction of >= 0.22 Point in HAQ Score at Week 12. | Week 12 | The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. The proportion of participants achieving a clinically important reduction of \>= 0.22 point in HAQ (disease-specific questionnaire) at Week 24 was evaluated. HAQ was assessed using the set of observed cases (OC) at each assessment time. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement. |
| Percentage of Participants Achieving a Clinically Important Increase of >=5 Points in the SF-36 Physical and Mental Component Scores at Weeks 12 and 24. | Week 12 and 24 | SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time. |
| Change in HAQ Score From Screening to Weeks 12 and 24 | Baseline, Week 12, Week 24 | The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. The number of participants achieving a clinically important reduction of \>= 0.22 point in HAQ (disease-specific questionnaire) at Week 24 was evaluated. HAQ was assessed using the set of observed cases (OC) at each assessment time. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement. |
| Number of Participants With Infusion Reactions, Infectious Events and / or Other Adverse Events in the 24 Weeks After the Start of Treatment. | Up to 24 Weeks | An infusion reaction is defined as an adverse event that occurs during infusion or within 24 hours after infusion of Rituximab. All infectious events, whether considered related or not to Rituximab, were collected for the safety analysis of the study. An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. |
Countries
Brazil
Participant flow
Recruitment details
A total of 95 participants were screened for eligibility between July 2009 and December 2011 at 16 centers in Brazil.
Pre-assignment details
Out of 95 participants, 72 who answered at least one short form 36 (SF-36) questionnaire made up the Intent-to-treat (ITT) population
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Participants with rheumatoid arthritis, who were treated with rituximab according to standard medical practice, were included in this cohort. | 72 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Infusion reaction at first infusion | 1 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Participant didn't perform visit Week 12 | 1 |
| Overall Study | Participant didn't perform visit Week 24 | 1 |
| Overall Study | Protocol Violation | 6 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 65 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 72 |
| serious Total, serious adverse events | 2 / 72 |
Outcome results
Primary
Mean Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 24
SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time.
Time frame: Baseline and Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = number of participants analyzed for a given component of SF-36.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 24 | Physical component score, n = 36 | 14.6 scores on a scale | Standard Error 2.5 |
| Rituximab | Mean Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 24 | Mental component score, n = 38 | 9.8 scores on a scale | Standard Error 3.8 |
Comparison: Physical component score at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA).p-value: <0.001ANOVA
Comparison: Mental component score at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA).p-value: =0.014ANOVA
Primary
Percentage of Participants Achieving an Improvement of at Least 0.22 Units in Health Assessment Questionnaire (HAQ) at Week 24
The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. The proportion of participants achieving a clinically important reduction of \>= 0.22 point in HAQ (disease-specific questionnaire) at Week 24 was evaluated. HAQ was assessed using the set of observed cases (OC) at each assessment time. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement.
Time frame: Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Percentage of Participants Achieving an Improvement of at Least 0.22 Units in Health Assessment Questionnaire (HAQ) at Week 24 | 57.9 Percentage |
Secondary
Change in HAQ Score From Screening to Weeks 12 and 24
The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. The number of participants achieving a clinically important reduction of \>= 0.22 point in HAQ (disease-specific questionnaire) at Week 24 was evaluated. HAQ was assessed using the set of observed cases (OC) at each assessment time. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Change in HAQ Score From Screening to Weeks 12 and 24 | Week 12 (n = 40) | -0.22 Units on a scale | Standard Error 0.08 |
| Rituximab | Change in HAQ Score From Screening to Weeks 12 and 24 | Week 24 (n = 38) | -0.31 Units on a scale | Standard Error 0.09 |
Comparison: Change in HAQ score from screening to Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.011ANOVA
Comparison: Change in HAQ score from screening to Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.001ANOVA
Secondary
Change in Pain Scale (100-mm VAS) From Screening to Weeks 12 and 24
Visual Analogue Scale (VAS) is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change from Screening=scores at observation minus score at Screening. An increase in score from Screening represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. The change in pain scale was analyzed for the set of observed cases (OC) at each assessment time.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Change in Pain Scale (100-mm VAS) From Screening to Weeks 12 and 24 | Week 12 (n = 40) | -17.9 Units on a scale | Standard Error 3.7 |
| Rituximab | Change in Pain Scale (100-mm VAS) From Screening to Weeks 12 and 24 | Week 24 (n = 37) | -20.7 Units on a scale | Standard Error 3.6 |
Comparison: Change in pain scale from screening to Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Comparison: Change in pain scale from screening to Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Secondary
Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24
SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed for a particular domain of SF-36.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, Physical functioning domain, n = 39 | 7.2 scores on a scale | Standard Error 4.3 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, Physical functioning domain, n = 38 | 7.6 scores on a scale | Standard Error 2.7 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, Role physical domain, n = 39 | 15.4 scores on a scale | Standard Error 5.5 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, Role physical domain, n = 38 | 21.6 scores on a scale | Standard Error 4.7 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, Bodily pain domain, n = 40 | 14.2 scores on a scale | Standard Error 4.1 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, Bodily pain domain, n = 37 | 17.6 scores on a scale | Standard Error 3.2 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, General health domain, n = 40 | 6.7 scores on a scale | Standard Error 3.7 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, General health domain, n = 37 | 7.7 scores on a scale | Standard Error 4.1 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, Vitality domain, n = 40 | 6.9 scores on a scale | Standard Error 2.8 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, Vitality domain, n = 38 | 7.4 scores on a scale | Standard Error 3.7 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, Social functioning domain, n = 40 | 15 scores on a scale | Standard Error 4.4 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, Social functioning domain, n = 38 | 15.5 scores on a scale | Standard Error 4.9 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, Role emotional domain, n = 39 | 12.4 scores on a scale | Standard Error 4.8 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, Role emotional domain, n = 38 | 7.7 scores on a scale | Standard Error 5.3 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 12, Mental health domain, n = 40 | 8 scores on a scale | Standard Error 3.4 |
| Rituximab | Change in SF-36 Domain Scores From Screening to Week (Wk) 12 and 24 | Wk 24, Mental health domain, n = 38 | 8.8 scores on a scale | Standard Error 3.9 |
Comparison: Role physical domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.008ANOVA
Comparison: Physical functioning domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.102ANOVA
Comparison: Physical functioning domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.008ANOVA
Comparison: Role physical domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Comparison: Bodily pain domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.002ANOVA
Comparison: Bodily pain domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Comparison: General health domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.077ANOVA
Comparison: General health domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.068ANOVA
Comparison: Vitality domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.018ANOVA
Comparison: Vitality domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.053ANOVA
Comparison: Social functioning domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.002ANOVA
Comparison: Social functioning domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.003ANOVA
Comparison: Role emotional domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.015ANOVA
Comparison: Role emotional domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.154ANOVA
Comparison: Mental health domain at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.024ANOVA
Comparison: Mental health domain at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.029ANOVA
Secondary
Change in SF-36 Physical and Mental Component Scores From Screening to Week 12
SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time.
Time frame: Baseline, Week 12
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed for a particular component of SF-36.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Change in SF-36 Physical and Mental Component Scores From Screening to Week 12 | SF-36 Physical component score (n = 39) | 11.2 scores on a scale | Standard Error 3.1 |
| Rituximab | Change in SF-36 Physical and Mental Component Scores From Screening to Week 12 | SF-36 Mental component score (n = 39) | 10.9 scores on a scale | Standard Error 3.1 |
Comparison: Physical component score at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.001ANOVA
Comparison: Mental component score at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.001ANOVA
Secondary
Mean Change From Baseline in C-reactive Protein (CRP).
CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as Rheumatoid Arthritis.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Change From Baseline in C-reactive Protein (CRP). | Week 24 (n = 36) | -0.5 mg/L | Standard Error 1 |
| Rituximab | Mean Change From Baseline in C-reactive Protein (CRP). | Week 12 (n = 37) | -0.3 mg/L | Standard Error 0.9 |
Comparison: Mean change from Baseline in CRP at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.744ANOVA
Comparison: Mean change from Baseline in CRP at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.646ANOVA
Secondary
Mean Change From Baseline in Disease Activity Score 28 Joints (DAS28) Score
DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to disease activity. A DAS28 score of less than or equal to (=\<) 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Change From Baseline in Disease Activity Score 28 Joints (DAS28) Score | Week 12 (n = 48) | -1.5 Units on a scale | Standard Error 0.2 |
| Rituximab | Mean Change From Baseline in Disease Activity Score 28 Joints (DAS28) Score | Week 24 (n = 46) | -1.7 Units on a scale | Standard Error 0.2 |
Comparison: Mean change from Baseline in DAS28 at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Comparison: Mean change from Baseline in DAS28 at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Secondary
Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
Erythrocyte Sedimentation Rate is an acute phase reactant and a measure of inflammation.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 12 (n = 48) | -7.5 mm/hr | Standard Error 3.1 |
| Rituximab | Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 24 (n = 46) | -11.5 mm/hr | Standard Error 3.7 |
Comparison: Mean change from Baseline in ESR at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.021ANOVA
Comparison: Mean change from Baseline in ESR at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: =0.003ANOVA
Secondary
Mean Change From Baseline in Patient Global Assessment (100 mm VAS)
The Physician's Global Assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity).Change from Baseline = scores at observation minus score at Baseline. An increase in score from Baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Change From Baseline in Patient Global Assessment (100 mm VAS) | Week 12 (n = 58) | -25.6 Units on a scale | Standard Error 3.2 |
| Rituximab | Mean Change From Baseline in Patient Global Assessment (100 mm VAS) | Week 24 (n = 56) | -23.6 Units on a scale | Standard Error 3.3 |
Comparison: Mean change from Baseline in patient global assessment at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Comparison: Mean change from Baseline in patient global assessment at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Secondary
Mean Change From Baseline in Swollen Joint Count (SJC)
A swollen joint count is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). It reflects the amount of inflamed synovial tissue.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Change From Baseline in Swollen Joint Count (SJC) | Week 12 (n = 58) | -5.2 Number of swollen joints | Standard Error 0.6 |
| Rituximab | Mean Change From Baseline in Swollen Joint Count (SJC) | Week 24 (n = 56) | -5.1 Number of swollen joints | Standard Error 0.7 |
Comparison: Mean change from Baseline in SJC at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Comparison: Mean change from Baseline in SJC at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Secondary
Mean Change From Baseline in Tender Joint Count (TJC)
A tender joint count is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). It is associated more with the level of pain.
Time frame: Baseline, Week 12, Week 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = the number of participants analyzed at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab | Mean Change From Baseline in Tender Joint Count (TJC) | Week 12 (n = 58) | -6 Number of tender joints | Standard Error 0.8 |
| Rituximab | Mean Change From Baseline in Tender Joint Count (TJC) | Week 24 (n = 56) | -7 Number of tender joints | Standard Error 0.9 |
Comparison: Mean change from Baseline in TJC at Week 12: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Comparison: Mean change from Baseline in TJC at Week 24: The statistical hypothesis (H0) that the change is equal to 0 is evaluated using the Repeated Measures Analysis of Variance (ANOVA)p-value: <0.001ANOVA
Secondary
Number of Participants With Infusion Reactions, Infectious Events and / or Other Adverse Events in the 24 Weeks After the Start of Treatment.
An infusion reaction is defined as an adverse event that occurs during infusion or within 24 hours after infusion of Rituximab. All infectious events, whether considered related or not to Rituximab, were collected for the safety analysis of the study. An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Up to 24 Weeks
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Infusion Reactions, Infectious Events and / or Other Adverse Events in the 24 Weeks After the Start of Treatment. | Infusion reactions | 15 participants |
| Rituximab | Number of Participants With Infusion Reactions, Infectious Events and / or Other Adverse Events in the 24 Weeks After the Start of Treatment. | Infectious events | 5 participants |
| Rituximab | Number of Participants With Infusion Reactions, Infectious Events and / or Other Adverse Events in the 24 Weeks After the Start of Treatment. | Adverse events | 21 participants |
Secondary
Percentage of Participants Achieving a Clinically Important Increase of >=5 Points in the SF-36 Physical and Mental Component Scores at Weeks 12 and 24.
SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores were computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. SF-36 was assessed using the set of observed cases (OC) at each assessment time.
Time frame: Week 12 and 24
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire. n = number of participants analyzed for a given component of SF-36.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Percentage of Participants Achieving a Clinically Important Increase of >=5 Points in the SF-36 Physical and Mental Component Scores at Weeks 12 and 24. | Physical component score, Week 12, n = 39 | 74.4 Percentage |
| Rituximab | Percentage of Participants Achieving a Clinically Important Increase of >=5 Points in the SF-36 Physical and Mental Component Scores at Weeks 12 and 24. | Physical component score, Week 24, n = 36 | 69.4 Percentage |
| Rituximab | Percentage of Participants Achieving a Clinically Important Increase of >=5 Points in the SF-36 Physical and Mental Component Scores at Weeks 12 and 24. | Mental component score, Week 12, n = 39 | 74.4 Percentage |
| Rituximab | Percentage of Participants Achieving a Clinically Important Increase of >=5 Points in the SF-36 Physical and Mental Component Scores at Weeks 12 and 24. | Mental component score, Week 24, n = 38 | 65.8 Percentage |
Secondary
Percentage of Participants Achieving a Clinically Important Reduction of >= 0.22 Point in HAQ Score at Week 12.
The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. The proportion of participants achieving a clinically important reduction of \>= 0.22 point in HAQ (disease-specific questionnaire) at Week 24 was evaluated. HAQ was assessed using the set of observed cases (OC) at each assessment time. An improvement of 0.22 units in HAQ-DI was considered to be a clinically significant improvement.
Time frame: Week 12
Population: The ITT population included all screened participants who answered at least one SF-36 questionnaire.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Percentage of Participants Achieving a Clinically Important Reduction of >= 0.22 Point in HAQ Score at Week 12. | 47.5 Percentage |