A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis

Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52

Rate of progression in structural joint damage (PJD) by change in modified joint space narrowing (JSN) from screening to Week 52. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.

Time frame: Baseline and week 52

Change From Baseline in the Modified Total Sharp Score at Week 24

The modified total sharp score is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.

Time frame: Baseline, Week 24

Change From Baseline in the Total Erosion Score at Week 24

Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The Total Erosion Score at Week 24 - Total Erosion Score at baseline is calculated.

Time frame: Baseline, Week 24

Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24

Joint Space Narrowing is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.

Time frame: Baseline, Week 24

Percentage of Participants Without Radiographic Progression at Week 24

Percentage of patients without radiographic progression at Week 24 defined as change in total modified Sharp score (TMSS) ≤ 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.

Time frame: Baseline, Week 24

Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52

To achieve an ACR50 response requires at least a 50% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 50% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Time frame: Week 52

Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52

DAS28-ESR is calculated from the following formula: (0.56 \* TJC) + (0.28 \* SJC) + (0.70 \* ln ESR) + (0.014 \* GH) TJC = tender joint count, based on 28 joints SJC = swollen joint count, based on 28 joints ESR = erythrocyte sedimentation rate in mm/h GH = patient's global assessment of disease activity A DAS28-ESR score of 5.1 or above is considered to indicate high disease activity. Patients can also be defined as having low disease activity (DAS28-ESR ≤ 3.2) or remission (DAS28-ESR \< 2.6).

Time frame: Baseline, Week 52

Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52

To achieve an ACR70 response requires at least a 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Time frame: Baseline, Week 52

Percentage of Participants With DAS28-ESR Remission at Week 52

The DAS28-4(ESR) score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28-4(ESR) scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6

Time frame: Week 52

Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52

European League Against Rheumatism (EULAR) criteria reflects an improvement in disease activity and an attainment of a lower degree of disease activity. A good response is defined as an improvement in the DAS28-ESR of \> 1.2 compared with baseline, and attainment of a DAS28-ESR of \< 3.2.

Time frame: Baseline, Week 52

The Percentage of Participants With Major Clinical Response at Week 52

Major clinical response is defined as a continuous six-month period of success by the ACR70. ACR70= 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in 3 of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Time frame: Week 52

Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52

The DAS28-4(ESR) score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28-4(ESR) scores range from 0 - 10. Low disease activity is defined as achieving a DAS28-ESR score of less than or equal to 3.2

Time frame: Week 52

Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52

To achieve an ACR20 response requires at least a 20% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 20% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Time frame: Baseline, Week 52

Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52

To achieve an ACR90 response requires at least a 90% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 90% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Time frame: Baseline, Week 52

Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.

Time frame: Baseline, Week 52

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip,and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A negative change from baseline indicates improvement.

Time frame: Baseline, Week 52

Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement. Means are adjusted for baseline value, Rheumatoid Factor status and region.

Time frame: Baseline, Week 52, Week 104

Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement. Means are adjusted for baseline value, Rheumatoid Factor status and region.

Time frame: Baseline, Weeks 52, Week 104

Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has at least two component questions. There are four possible responses for each component on a scale of 0 (without difficulty) to 3 (unable to do). Higher scores=greater dysfunction. Improved:HAQ-DI score change \<=-0.22 Unchanged:HAQ-DI score change -0.22 to 0.22 Worsened:HAQ score =\> 0.22

Time frame: Baseline, Week 52

Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52

MCID is defined as a change from baseline in SF-36 Physical Health Component Score of \>5.42. SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

Time frame: Baseline, Week 52

Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52

MCID is defined as a change from baseline in SF-36 Mental Health Component Score of \>6.33. SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

Time frame: Baseline, Week 52

Change From Baseline in the Modified Total Sharp Score at Week 104

The modified total sharp score is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.

Time frame: Baseline, Week 104

Change From Baseline in the Total Erosion Score at Week 104

Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The change from the score at baseline to week 104 is calculated.

Time frame: Baseline, Week 104

Percentage of Participants Without Radiographic Progression at Week 104

Percentage of patients without radiographic progression at Week 104, defined as change in total modified Sharp score (TMSS) ≤ 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.

Time frame: Baseline, Week 104

Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104

Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The score at baseline is compared to the score at week 104. No progression is defined as a change from score at screening to week 104 ≤0.

Time frame: Week 104

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A negative change from baseline indicates improvement.

Time frame: Baseline, Week 104