Trial Outcomes & Findings for Safety and Tolerability of Rituxan With Methotrexate and Etanercept or Methotrexate and Adalimumab in Patients With Active Rheumatoid Arthritis (NCT NCT00298272)

Last Updated: 2015-09-28

Results Overview

An infection was considered serious if it required intravenous (IV) antibiotics or met the regulatory definition of a serious adverse event (SAE). An SAE was any event that resulted in death, resulted in a congenital anomaly in a child of a participant in the study, caused or prolonged an inpatient hospitalization, resulted in significant or persistent disability, or was considered by the investigator to be an important medical event that may have required intervention to prevent any of the above-listed outcomes.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Through Week 24

Results posted on

2015-09-28

Participant Flow

Participants were enrolled at 17 sites in the United States.

After 24 weeks, participants continued post-treatment follow-up (PTFU) visits through Week 56, and entered a 48-week Safety Follow-Up (SFU). At any time between Week 24 and Week 40 of PTFU, eligible participants could enter the rituximab open label (OL) arm, and "restart" the 56-week treatment/follow-up schedule prior to the 48-week SFU.

Participant milestones

Participant milestones
Measure	Double-blind/Open Label Rituximab The double-blind rituximab treatment group received rituximab 500 mg by intravenous (IV) infusion on Day 1 and Day 15. After 24 weeks (primary endpoint completion), participants continued post-treatment follow-up (PTFU) visits through Week 56, and entered a 48-week Safety Follow-Up (SFU). At any time between Week 24 and Week 40 of PTFU, eligible participants could enter the rituximab open label (OL) arm, and "restart" the 56-week treatment/follow-up schedule (rituximab 500 mg by IV infusion on Day 1 and Day 15) prior to the 48-week SFU.	Double-blind Placebo/Open Label Rituximab The double-blind placebo treatment group received saline solution IV on Day 1 and Day 15. After 24 weeks (primary endpoint completion), participants continued post-treatment follow-up (PTFU) visits through Week 56, and entered a 48-week Safety Follow-Up (SFU). At any time between Week 24 and Week 40 of PTFU, eligible participants could enter the rituximab open label (OL) arm, and "restart" the 56-week treatment/follow-up schedule (rituximab 500 mg by IV infusion on Day 1 and Day 15) prior to the 48-week SFU.
Double-blind Phase STARTED	36	18
Double-blind Phase Safety Population	33	18
Double-blind Phase Completed to Week 24	31	18
Double-blind Phase Completed to Week 56	8	3
Double-blind Phase COMPLETED	28	18
Double-blind Phase NOT COMPLETED	8	0
Open Label Retreatment Phase STARTED	22	16
Open Label Retreatment Phase Completed to Week 24	22	15
Open Label Retreatment Phase Completed to Week 56	13	12
Open Label Retreatment Phase COMPLETED	13	12
Open Label Retreatment Phase NOT COMPLETED	9	4
Safety Follow-up Phase STARTED	22	17
Safety Follow-up Phase COMPLETED	18	13
Safety Follow-up Phase NOT COMPLETED	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-blind/Open Label Rituximab The double-blind rituximab treatment group received rituximab 500 mg by intravenous (IV) infusion on Day 1 and Day 15. After 24 weeks (primary endpoint completion), participants continued post-treatment follow-up (PTFU) visits through Week 56, and entered a 48-week Safety Follow-Up (SFU). At any time between Week 24 and Week 40 of PTFU, eligible participants could enter the rituximab open label (OL) arm, and "restart" the 56-week treatment/follow-up schedule (rituximab 500 mg by IV infusion on Day 1 and Day 15) prior to the 48-week SFU.	Double-blind Placebo/Open Label Rituximab The double-blind placebo treatment group received saline solution IV on Day 1 and Day 15. After 24 weeks (primary endpoint completion), participants continued post-treatment follow-up (PTFU) visits through Week 56, and entered a 48-week Safety Follow-Up (SFU). At any time between Week 24 and Week 40 of PTFU, eligible participants could enter the rituximab open label (OL) arm, and "restart" the 56-week treatment/follow-up schedule (rituximab 500 mg by IV infusion on Day 1 and Day 15) prior to the 48-week SFU.
Double-blind Phase Adverse Event	2	0
Double-blind Phase Failure to Return	2	0
Double-blind Phase Protocol Violation	2	0
Double-blind Phase Withdrawal by Subject	2	0
Open Label Retreatment Phase Adverse Event	1	2
Open Label Retreatment Phase Insufficient Therapeutic Response	2	1
Open Label Retreatment Phase Failure to Return	1	0
Open Label Retreatment Phase Protocol Violation	2	1
Open Label Retreatment Phase Withdrawal by Subject	1	0
Open Label Retreatment Phase Administrative/Other Reason	2	0
Safety Follow-up Phase Failure to Return	1	1
Safety Follow-up Phase Withdrawal by Subject	2	2
Safety Follow-up Phase Administrative/Other Reason	1	1

Baseline Characteristics

Safety and Tolerability of Rituxan With Methotrexate and Etanercept or Methotrexate and Adalimumab in Patients With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind/Open Label Rituximab n=33 Participants The double-blind rituximab treatment group received rituximab 500 mg by intravenous (IV) infusion on Day 1 and Day 15. After 24 weeks (primary endpoint completion), participants continued post-treatment follow-up (PTFU) visits through Week 56, and entered a 48-week Safety Follow-Up (SFU). At any time between Week 24 and Week 40 of PTFU, eligible participants could enter the rituximab open label (OL) arm, and "restart" the 56-week treatment/follow-up schedule (rituximab 500 mg by IV infusion on Day 1 and Day 15) prior to the 48-week SFU.	Double-blind Placebo/Open Label Rituximab n=18 Participants The double-blind placebo treatment group received saline solution IV on Day 1 and Day 15. After 24 weeks (primary endpoint completion), participants continued post-treatment follow-up (PTFU) visits through Week 56, and entered a 48-week Safety Follow-Up (SFU). At any time between Week 24 and Week 40 of PTFU, eligible participants could enter the rituximab open label (OL) arm, and "restart" the 56-week treatment/follow-up schedule (rituximab 500 mg by IV infusion on Day 1 and Day 15) prior to the 48-week SFU.	Total n=51 Participants Total of all reporting groups
Age, Continuous	49.7 Years STANDARD_DEVIATION 12.1 • n=5 Participants	50.4 Years STANDARD_DEVIATION 11.4 • n=7 Participants	50.0 Years STANDARD_DEVIATION 11.7 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	17 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Years since rheumatoid arthritis (RA) diagnosis	10.3 Years STANDARD_DEVIATION 6.7 • n=5 Participants	10.7 Years STANDARD_DEVIATION 7.5 • n=7 Participants	10.5 Years STANDARD_DEVIATION 6.9 • n=5 Participants
Number of Prior Tumor Necrosis Factor (TNF) Inhibitors 1	32 participants n=5 Participants	18 participants n=7 Participants	50 participants n=5 Participants
Number of Prior Tumor Necrosis Factor (TNF) Inhibitors 2	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
C-Reactive Protein	0.97 mg/dL n=5 Participants	0.83 mg/dL n=7 Participants	0.92 mg/dL n=5 Participants
Swollen and Tender Joints Swollen joints	16.9 Joint counts n=5 Participants	14.2 Joint counts n=7 Participants	16.0 Joint counts n=5 Participants
Swollen and Tender Joints Tender joints	25.6 Joint counts n=5 Participants	22.8 Joint counts n=7 Participants	24.6 Joint counts n=5 Participants

PRIMARY outcome

Timeframe: Through Week 24

Population: The Safety Population consisted of all participants who received any part of an infusion of rituximab or placebo.

Outcome measures

Outcome measures
Measure	Rituximab n=33 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=18 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Proportion of Participants With at Least One Serious Infection Through Week 24	0.03 proportion of participants	0.00 proportion of participants

PRIMARY outcome

Timeframe: Through Week 24

Population: The Safety Population consisted of all participants who received any part of an infusion of rituximab or placebo.

Infections were defined as adverse events that map to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of "infections and infestations" and also included other infectious events that do not map to this SOC (e.g., cholecystitis, pleurisy, conjunctivitis, acne, tongue ulceration). Participants with multiple infections were calculated only once. The severity of all reported adverse events, including infections, was graded and reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events. This scale defines the severity of an adverse event as follows: Grade 1 = a mild adverse event, Grade 2 = a moderate adverse event, Grade 3 = a severe adverse event, and Grade 4 = a life-threatening or disabling adverse event.

Outcome measures

Outcome measures
Measure	Rituximab n=33 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=18 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Number of Participants With Any Infections or Any Grade 3/4 Infections Through Week 24 Any Infection	18 participants	11 participants
Number of Participants With Any Infections or Any Grade 3/4 Infections Through Week 24 Any Grade 3/4 Infection	3 participants	0 participants

PRIMARY outcome

Timeframe: Week 24

Population: Participants in the Safety Population with at least 1 infection. The Safety Population consisted of all participants who received any part of an infusion of rituximab or placebo.

Outcome measures

Outcome measures
Measure	Rituximab n=18 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=11 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Maximum Duration of Infections Through Week 24	12.6 days Standard Deviation 9.6 • Interval 151.6 to 306.44	14.5 days Standard Deviation 5.2 • Interval 215.7 to 465.23

PRIMARY outcome

Timeframe: Through Week 24

Population: The Safety Population consisted of all participants who received any part of an infusion of rituximab or placebo.

An AE was any sign (including an abnormal laboratory result that the investigator determined to be clinically significant), symptom, or diagnosis/disease that is unfavorable or unintended, that was new, or if pre-existing, worsened in a participant and that did not necessarily have a causal relationship with the treatment. An SAE was any event that resulted in death, resulted in a congenital anomaly in a child of a participant in the study, caused or prolonged an inpatient hospitalization, resulted in significant or persistent disability, or was considered by the investigator to be an important medical event that may have required intervention to prevent any of the above-listed outcomes.

Outcome measures

Outcome measures
Measure	Rituximab n=33 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=18 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Week 24 Any AE	31 participants	15 participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Week 24 Any SAE	2 participants	0 participants

PRIMARY outcome

Timeframe: Through Week 24

Population: The Safety Population consisted of all participants who received any part of an infusion of rituximab or placebo.

The following immunological assessments were conducted: autoantibody concentrations for RF, anti-cyclic-citrullinated peptide (CCP) antibody concentrations, quantitative immunoglobulin levels, and lymphocyte assessments of T- and B-cell populations, determined using whole blood expanded fluorescent-activated cell sorter (FACS) analysis. The following laboratory assessments were performed: hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC) with differential, and platelet counts; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total protein, albumin, total bilirubin, blood urea nitrogen (BUN), uric acid, creatinine, random glucose, potassium, sodium, chloride, calcium, and phosphorous; blood, protein, and glucose (microscopic examination, if abnormal and applicable).

Outcome measures

Outcome measures
Measure	Rituximab n=33 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=18 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Number of Participants With Clinically Significant Immunological and Laboratory Assessment Findings	0 participants	0 participants

SECONDARY outcome

Timeframe: Week 24

Population: The Safety Population consisted of all participants who received any part of an infusion of rituximab or placebo. Missing data were imputed using the nonresponder method, in which a participant with missing data at the visit being analyzed was considered a nonresponder.

An ACR20 response is defined as a 20% reduction in the number of both swollen and tender joints, and a 20% reduction in the score or results of at least 3 of the following 5 core set measurement tools: 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.

Outcome measures

Outcome measures
Measure	Rituximab n=33 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=18 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Proportion of Participants Achieving an American College of Rheumatology 20 (ACR20) Response at Week 24	0.30 proportion of participants	0.17 proportion of participants

SECONDARY outcome

Timeframe: Week 24

An ACR50 response is defined as a 50% reduction in the number of both swollen and tender joints, and a 50% reduction in the score or results of at least 3 of the following 5 core set measurement tools: 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.

Outcome measures

Outcome measures
Measure	Rituximab n=33 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=18 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Proportion of Participants Achieving an American College of Rheumatology 50 (ACR50) Response at Week 24	0.12 proportion of participants	0.06 proportion of participants

SECONDARY outcome

Timeframe: Week 24

An ACR70 response is defined as a 70% reduction in the number of both swollen and tender joints, and a 70% reduction in the score or results of at least 3 of the following 5 core set measurement tools: 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.

Outcome measures

Outcome measures
Measure	Rituximab n=33 Participants The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Placebo n=18 Participants The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Proportion of Participants Achieving an American College of Rheumatology 70 (ACR70) Response at Week 24	0.00 proportion of participants	0.00 proportion of participants

Adverse Events

Double-Blind Rituximab

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Double-Blind Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Cumulative Rituximab

Serious events: 8 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-Blind Rituximab n=33 participants at risk The rituximab treatment group received rituximab 500 mg by intravenous infusion (IV) on Day 1 and Day 15. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Double-Blind Placebo n=18 participants at risk The placebo treatment group received saline solution IV on Day 1 and Day 15. Prior to each infusion of placebo, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.	Cumulative Rituximab n=49 participants at risk The cumulative rituximab treatment group included all participants who received rituximab at any time during the study, including participants who received rituximab in the double-blind period and did not participate in the OL period, those who received placebo in the double-blind period and rituximab in the OL, and those who received rituximab in the double-blind and OL periods. Prior to rituximab infusion, participants were premedicated with methylprednisolone 100 mg IV. Participants were also to receive a stable dose of folate ≥5 mg weekly.
Cardiac disorders Coronary Artery Occlusion	3.0% 1/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Infections and infestations Pneumonia	3.0% 1/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Infections and infestations Arthritis Infective	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	8.2% 4/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Infections and infestations Cellulitis	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Infections and infestations Osteomyelitis	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Blood and lymphatic system disorders Neutropenia	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Nervous system disorders Dizziness	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Nervous system disorders Headache	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Respiratory, thoracic and mediastinal disorders Interstitial Lung Disease	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Gastrointestinal disorders Impaired Gastric Emptying	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Gastrointestinal disorders Nausea	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
Musculoskeletal and connective tissue disorders Systemic Lupus Erythematosus	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).
General disorders Asthenia	0.00% 0/33 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	0.00% 0/18 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).	2.0% 1/49 • For Double-Blind Rituximab and Double-Blind Placebo reporting groups, nonserious AE data and SAE data are presented through the Week 24 treatment phase (primary endpoint completion). See Additional Description (below) for Cumulative Rituximab time frame. For Cumulative Rituximab reporting group, nonserious AEs were captured only through Week 56. Serious adverse events (SAEs) were captured during treatment and post-treatment periods, through the safety follow-up (SFU) period (48 weeks) and the extended safety follow-up (ESFU; 1760 days).

Other adverse events

Additional Information

Biogen Idec Study Medical Director

Biogen Idec

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER