Trial Outcomes & Findings for Safety of Switching From Rituximab to Ocrelizumab in MS Patients (NCT NCT02980042)

Results Overview

The investigators will report the proportion of infusions with \>= 1 IRR (infusion-related reaction) between the switching and comparator groups. Data was collected at Day 1, Day 15, and Week 24 and combined to determine the overall proportion of IRRs over the life of the study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

200 participants

Primary outcome timeframe

Day 1, Day 15, Week 24

Results posted on

2021-07-21

Participant Flow

Participant milestones

Participant milestones
Measure	Switching Group 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.
Overall Study STARTED	100	100
Overall Study COMPLETED	93	100
Overall Study NOT COMPLETED	7	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Switching Group 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.
Overall Study Lost to Follow-up	5	0
Overall Study Insurance issues/treatment plan changes	2	0

Baseline Characteristics

EDSS was not collected for the comparator group at baseline. EDSS is only available for the Switching group.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Switching Group n=100 Participants 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=100 Participants Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Total n=200 Participants Total of all reporting groups
Age, Continuous	45.30 years STANDARD_DEVIATION 11.01 • n=100 Participants	43.82 years STANDARD_DEVIATION 9.97 • n=100 Participants	44.56 years STANDARD_DEVIATION 10.50 • n=200 Participants
Sex: Female, Male Female	68 Participants n=100 Participants	75 Participants n=100 Participants	143 Participants n=200 Participants
Sex: Female, Male Male	32 Participants n=100 Participants	25 Participants n=100 Participants	57 Participants n=200 Participants
Race/Ethnicity, Customized Hispanic or Latino	8 Participants n=100 Participants	7 Participants n=100 Participants	15 Participants n=200 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	92 Participants n=100 Participants	89 Participants n=100 Participants	181 Participants n=200 Participants
Race/Ethnicity, Customized Other	4 Participants n=100 Participants	5 Participants n=100 Participants	9 Participants n=200 Participants
Race/Ethnicity, Customized Black/African American	5 Participants n=100 Participants	12 Participants n=100 Participants	17 Participants n=200 Participants
Race/Ethnicity, Customized White	90 Participants n=100 Participants	82 Participants n=100 Participants	172 Participants n=200 Participants
Race/Ethnicity, Customized Asian	1 Participants n=100 Participants	0 Participants n=100 Participants	1 Participants n=200 Participants
Race/Ethnicity, Customized Native American	0 Participants n=100 Participants	1 Participants n=100 Participants	1 Participants n=200 Participants
Expanded Disability Status Scale (EDSS)	3.5 units on a scale n=100 Participants • EDSS was not collected for the comparator group at baseline. EDSS is only available for the Switching group.	—	3.5 units on a scale n=100 Participants • EDSS was not collected for the comparator group at baseline. EDSS is only available for the Switching group.
Patient Determined Disease Steps (PDDS)	3 units on a scale n=100 Participants • PDDS was not collected for the comparator group. PDDS is only available for the Switching group.	—	3 units on a scale n=100 Participants • PDDS was not collected for the comparator group. PDDS is only available for the Switching group.
Disease Duration	11.20 years STANDARD_DEVIATION 7.91 • n=100 Participants	11.32 years STANDARD_DEVIATION 7.97 • n=100 Participants	11.26 years STANDARD_DEVIATION 7.92 • n=200 Participants
Number of Years on rituximab	2.38 years STANDARD_DEVIATION 1.37 • n=100 Participants	2.44 years STANDARD_DEVIATION 1.45 • n=100 Participants	2.41 years STANDARD_DEVIATION 1.41 • n=200 Participants

PRIMARY outcome

Timeframe: Day 1, Day 15, Week 24

Population: The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. There were a total of 300 infusions in the Switching group and 200 in the Comparator group. Proportion of IRRs are taken out of total number of infusions.

The investigators will report the proportion of infusions with \>= 1 IRR (infusion-related reaction) between the switching and comparator groups. Data was collected at Day 1, Day 15, and Week 24 and combined to determine the overall proportion of IRRs over the life of the study.

Outcome measures

Outcome measures
Measure	Switching Group n=300 Infusions 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=200 Infusions Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Proportion of Infusions With >= 1 IRR Between the Switching and Comparator Groups	10 percentage of infusions with IRRs	14 percentage of infusions with IRRs	—

PRIMARY outcome

Timeframe: Pre-study (Enrollment), Day 1, Day 15, Week 24

Population: Participants in the comparator group were assessed to have had two pre-study infusions at time of enrollment. A retrospective chart review was conducted to determine the number of IRRs experienced during these previous infusions. The collected number of IRRs was used as a comparison measure against the switching group.

The investigators will report the difference in the total number of IRRs after each infusion of ocrelizumab compared to combined rituximab infusions in the comparator group.

Outcome measures

Outcome measures
Measure	Switching Group n=100 Infusions 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=200 Infusions Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group. Pre-study infusions	—	28 Infusions	—
Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group. Day 1	14 Infusions	—	—
Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group. Day 15	4 Infusions	—	—
Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group. Week 24	12 Infusions	—	—

PRIMARY outcome

Timeframe: Day 1, pre-study infusions

Population: The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions prior to enrollment (as assessed via retrospective chart review). This analysis is comparing IRRs of the Switching group's Day 1 infusion, with the comparator group's pre-study infusion 1 and 2.

The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .

Outcome measures

Outcome measures
Measure	Switching Group n=100 Infusions 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=200 Infusions Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions No Infusion Reaction	86 Infusions	172 Infusions	—
Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 1 Infusion Reaction	8 Infusions	3 Infusions	—
Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 2 Infusion Reaction	6 Infusions	25 Infusions	—
Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 3, 4, or 5 Infusion Reaction	0 Infusions	0 Infusions	—

PRIMARY outcome

Timeframe: Day 15, pre-study infusions

Population: The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. Proportion of IRRs are taken out of total number of infusions. This analysis is comparing IRRs of the Switching group's Day 15 infusion, with the comparator group's pre-study infusion 1 and 2.

The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion.

Outcome measures

Outcome measures
Measure	Switching Group n=100 Infusions 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=200 Infusions Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions No Infusion Reaction	96 Infusions	172 Infusions	—
Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 1 Infusion Reaction	0 Infusions	3 Infusions	—
Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 2 Infusion Reaction	4 Infusions	25 Infusions	—
Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 3, 4, and 5 Infusion Reaction	0 Infusions	0 Infusions	—

PRIMARY outcome

Timeframe: Week 24, pre-study infusions

Population: The Switching group received 3 infusions (Day 1, Day 15 and week 24), and the Comparator group received 2 infusions. Proportion of IRRs are taken out of total number of infusions. This analysis is comparing IRRs of the Switching group's Week 24 infusion, with the comparator group's pre-study infusion 1 and 2.

The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .

Outcome measures

Outcome measures
Measure	Switching Group n=100 Infusions 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=200 Infusions Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions No Infusion Reaction	88 Infusions	172 Infusions	—
Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 1 Infusion Reaction	9 Infusions	3 Infusions	—
Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 2 Infusion Reaction	3 Infusions	25 Infusions	—
Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions Grade 3, 4, and 5 Infusion Reaction	0 Infusions	0 Infusions	—

PRIMARY outcome

Timeframe: Day 1, Day 15, Week 24

We will also compare the proportion of patients with an IRR following day 1 infusion versus the proportion of patients with an IRR at day 15 and month 6 infusions of ocrelizumab in the switching group.

Outcome measures

Outcome measures
Measure	Switching Group n=100 Participants 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=100 Participants Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion n=100 Participants 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Proportion of Patients With an IRR at Day 1 Versus Day 15 and Week 24 Infusions	14 Participants	4 Participants	12 Participants

SECONDARY outcome

Timeframe: Day 1 and Week 24

Population: Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.

Proportion of ocrelizumab patients who test positive for ocrelizumab anti-drug anti-bodies

Outcome measures

Outcome measures
Measure	Switching Group n=100 Participants 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=100 Participants Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Presence of Ocrelizumab Anti-drug Anti-bodies	1.00 percentage of patients Interval 0.03 to 5.45	1.00 percentage of patients Interval 0.03 to 5.45	—

SECONDARY outcome

Timeframe: Day 1 and Week 24

Population: Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.

Proportion of patients who test positive for rituximab anti-drug anti-bodies.

Outcome measures

Outcome measures
Measure	Switching Group n=100 Participants 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=100 Participants Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Presence of Rituximab Anti-drug Anti-bodies	16.00 percentage of patients Interval 8.81 to 23.19	7.00 percentage of patients Interval 2.86 to 13.89	—

SECONDARY outcome

Timeframe: Day 1, Week 24, 1 Year

Population: Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.

Proportion of patients with CD19% \<= 1%.

Outcome measures

Outcome measures
Measure	Switching Group n=98 Participants 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells	Comparator Group n=100 Participants Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line Rituximab: A chimeric monoclonal antibody against CD20.	Switching Group - Week 24 Infusion n=93 Participants 600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line. Ocrelizumab: A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
B Cell Depletion (CD19)	57.14 percentage of patients Interval 47.35 to 66.94	92.00 percentage of patients Interval 84.84 to 96.48	90.32 percentage of patients Interval 82.42 to 95.48

SECONDARY outcome

Timeframe: Day 1, Week 24, 1 Year

Population: Reporting proportions of patients. 95% confidence intervals calculating using either the standard Z score method or the exact Clopper-Pearson method as necessary.

Proportion of patients with CD20% \<= 1%