Each rituximab infusion was preceded by methylprednisolone 100 mg IV. Use of stable doses of oral corticosteroids was permitted (≤ 10 mg of prednisone or equivalent per day) as were stable doses of nonsteroidal anti-inflammatory drugs (NSAIDs).

An adverse event (AE) is any unfavorable and unintended sign, symptom, significantly abnormal laboratory finding, or disease temporally associated with the use of an investigational medical product or other protocol-imposed intervention. An AE was classified as an SAE if it: Resulted in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product; required or prolonged inpatient hospitalization; was life-threatening or considered a significant medical event by the investigator.

Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.

DAS 28-ESR was calculated using counts of tender and swollen joints (28 joints, 28TJC and 28SJC), a patient assessment (PA) of disease activity (DA) in previous 24 hours on a visual analog scale (no DA to maximum DA), and ESR at the current visit, using the following formula: 0.56 × 28TJC + 0.28 × 28SJC + 0.70 × ln(ESR) + 0.014 × PADA. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. DAS28-ESR Remission was defined as a DAS 28-ESR score of < 2.6. DAS28-ESR Low Disease Activity was defined as a DAS28-ESR score of ≤ 3.2.

Improvement in the post-baseline DAS 28-ESR score from baseline was used to determine the EULAR responses of moderate response and good response. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. For a post-baseline score ≤ 3.2, an improvement > 0.6 to ≤ 1.2 was a moderate response and ≥ 1.2 a good response. For a post-baseline score > 3.2 to ≤ 5.1, an improvement > 0.6 was a moderate response. For a post-baseline score > 5.1, an improvement ≥ 1.2 was a moderate response. A good response could not be achieved for post-baseline scores > 3.2.

The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.

Stage II patients received 2 doses of rituximab 500 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 500 mg given 14 days apart. Concomitant biological and non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.

Total of all reporting groups

Stage II patients received 2 doses of rituximab 500 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 500 mg given 14 days apart. Concomitant biological and non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.

The percentage of patients developing a SAE during or within 24 hours of a rituximab infusion is reported separately for each of the 2 infusions in the first course of treatment (Days 1 and 15) and the second course of treatment (optional retreatment during Weeks 24 to 40). See the Primary Outcome Measure for a definition of a SAE.

Safety population: All patients who were enrolled in the study and received any study drug (rituximab).

An adverse event (AE) is any unfavorable and unintended sign, symptom, significantly abnormal laboratory finding, or disease temporally associated with the use of an investigational medical product or other protocol-imposed intervention. An AE was classified as an SAE if it: Resulted in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product; required or prolonged inpatient hospitalization; was life-threatening or considered a significant medical event by the investigator.

Safety population: All patients who were enrolled in the study and received any study drug (rituximab).

Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.

Safety population: All patients who were enrolled in the study and received any study drug (rituximab).

DAS 28-ESR was calculated using counts of tender and swollen joints (28 joints, 28TJC and 28SJC), a patient assessment (PA) of disease activity (DA) in previous 24 hours on a visual analog scale (no DA to maximum DA), and ESR at the current visit, using the following formula: 0.56 × 28TJC + 0.28 × 28SJC + 0.70 × ln(ESR) + 0.014 × PADA. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. DAS28-ESR Remission was defined as a DAS 28-ESR score of < 2.6. DAS28-ESR Low Disease Activity was defined as a DAS28-ESR score of ≤ 3.2.

Safety population: All patients who were enrolled in the study and received any study drug (rituximab). There were 401 patients in the rituximab 1000 mg and 176 patients in the 500 mg safety populations. n = number of patients with non-missing DAS28-ESR last observation carried forward scores at Weeks 24 and 48 in the safety populations.

Improvement in the post-baseline DAS 28-ESR score from baseline was used to determine the EULAR responses of moderate response and good response. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. For a post-baseline score ≤ 3.2, an improvement > 0.6 to ≤ 1.2 was a moderate response and ≥ 1.2 a good response. For a post-baseline score > 3.2 to ≤ 5.1, an improvement > 0.6 was a moderate response. For a post-baseline score > 5.1, an improvement ≥ 1.2 was a moderate response. A good response could not be achieved for post-baseline scores > 3.2.

Safety population: All patients who were enrolled in the study and received any study drug (rituximab).

The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.

Safety population: All patients who were enrolled in the study and received any study drug (rituximab).

Stage II patients received 2 doses of rituximab 500 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 500 mg given 14 days apart. Concomitant biological and non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.