This is an Extension Study of the Roche P-trials to Investigate Safety and Effectiveness of Ocrelizumab in Participants With Multiple Sclerosis (MS)

Disability progression was defined as an increase of ≥ 1.0 point from the baseline Expanded Disability Status Scale (EDSS) score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as Functional Systems Score (FSSs). Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using Kaplan-Meier(K-M) method.

Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using K-M method.

Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using K-M method.

Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. isability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using K-M method.

Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. isability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, & ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. isability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated &scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated &scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at two scheduled visits at least 48 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at two scheduled visits at least 48 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.

The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel & bladder, visual, & cerebral) rated &scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations & information concerning ambulation & use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Participants were considered stable when the change from baseline in score was between -0.5 and +0.5, worsened when the change was > 0.5, and improved when the change in score was < -0.5. Percentages are rounded off.

The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel & bladder, visual, & cerebral) rated &scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations & information concerning ambulation & use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Participants were considered stable when the change from baseline in score was between -0.5 and +0.5 and worsened when the change was > 0.5. Percentages are rounded off.

The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel & bladder, visual, & cerebral) rated &scored as Functional Systems Score (FSSs). Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations & information concerning ambulation & use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM).

The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel & bladder, visual, & cerebral) rated &scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations & information concerning ambulation & use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Estimates are from analysis based on MMRM.

Sustained T25FWT was defined as a 24-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Median was analysed using K-M method.

Sustained T25FWT was defined as a 48-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Median was analysed using K-M method.

Sustained 9HPT was defined as a 24-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Median was analysed using K-M method.

Sustained 9HPT was defined as a 48-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Median was analysed using K-M method.

Sustained T25FWT was defined as a 24-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Percentage is rounded off.

Sustained T25FWT was defined as a 48-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Percentage is rounded off.

Sustained 9HPT was defined as a 24-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Percentage is rounded off.

Sustained 9HPT was defined as a 48-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Percentage is rounded off.

Disease activity was defined as at least one the following events: protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to MS. Symptoms must persist for > 24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications), and immediately be preceded by neurological stability for at least 30 days.); 24 weeks CDP based on increases in EDSS; a new T1 Gadolinium (Gd)-enhanced lesion; or a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI). The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated & scored as Functional Systems Score (FSSs). Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using K-M method.

A protocol-defined MS relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for >24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/ FSS, consistent with an increase of at least: ≥0.5 points on EDSS scale or ≥2 points on one of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual. or ≥1 point on two or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).

ARR=total number of relapses for all participants divided by the total years of drug exposure (from first day of infusion in parent study until LIBERTO week 96). Protocol-defined MS relapse=occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for >24 hours & not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/FSS, consistent with an increase of at least: ≥0.5 points on EDSS scale or ≥2 points on 1 of the FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual or ≥1 point on 2 or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual. EDSS scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Adjusted ARR is reported.

A protocol-defined MS relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for >24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/ FSS, consistent with an increase of at least: ≥0.5 points on EDSS scale or ≥2 points on one of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual. or ≥1 point on two or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death).

Percentage of participants with NEDA where disease activity = at least 1 of the following events: protocol defined relapse (PDR); 24 weeks CDP based on increases in EDSS while on treatment with ocrelizumab; a T1 Gd-enhanced lesion on MRI; or a new and/or enlarging T2 hyperintense lesion on MRI. PRD as defined in outcome measure 22. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS was 5.5 or less, and ≥ 0.5 when BS was above 5.5. Participants with EDSS of 0, progression was defined aschange of ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated & scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death).

Percentage of participants with NEDA where disease activity = at least 1 of the following events: protocol defined relapse (PDR); 24 weeks CDP based on increases in EDSS while on treatment with ocrelizumab; a T1 Gd-enhanced lesion on MRI; or a new and/or enlarging T2 hyperintense lesion on MRI. PRD as defined in outcome measure 22. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS was 5.5 or less, and ≥ 0.5 when BS was above 5.5. Participants with EDSS of 0, progression was defined aschange of ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated & scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death).

Percentage of participants with NEP =no progression sustained for at least 24 weeks on: CDP; 20% increase in timed T25FWT; 20% increase in timed 9HPT yearly & over the course of the study. CDP= increase of ≥ 1.0 point from the baseline EDSS score when BS= 5.5 or less, & ≥ 0.5 when the BS= above 5.5. For participants with an EDSS of 0, progression=change ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated & scored as FSSs. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). In T25FWT test participants walked to a 25 foot course as quickly & safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. In T25FWT & 9-HPT the longer it took complete test= higher scores, indicating deterioration.

Percentage of participants with NEPAD=no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse & no enlarging or new T2/ T1 Gd-enhancing lesion yearly & over the course of treatment. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS= 5.5 or less, & ≥ 0.5 when BS= above 5.5. Participants with EDSS of 0, progression=change ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated & scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death). In T25FWT test participants walked 25-foot course as quickly & safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place & remove pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the amount of time (in seconds) required was recorded. In T25FWT & 9-HPT the longer it took to complete test= higher scores, indicating deterioration.

SDMT test consists of a sequence of 110 symbols to be displayed in a maximum 90 seconds and a reference key legend (3 versions are available) with 9 symbols in a given order and their respective matching digits from 1 to 9. This test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds time. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement.

SDMT test consists of a sequence of 110 symbols to be displayed in a maximum 90 seconds and a reference key legend (3 versions are available) with 9 symbols in a given order and their respective matching digits from 1 to 9. This test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and a minimum of 0. Higher scores indicate improvement.

The rate was calculated by dividing the total number of T1 Gd-enhanced lesions for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. >1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (<2.5 vs >=2.5).

The rate was calculated by dividing the total number of new and/or enlarging T2 lesions for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. >1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (<2.5 vs >=2.5).

Estimates are from analysis based on mixed-effect model of repeated measures (MMRM)

The rate was calculated by dividing the total number of FLAIR for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. >1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (<2.5 vs >=2.5).

For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE week 8 has been reported.

For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE week 8 has been reported.

For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE Week 8 has been reported.

The WPAI employment status questionnaire is a PRO consisting of 6 items that assess working status, specifically the impact of MS on absenteeism, presentism, work productivity loss and activity impairment over the past 7 days. Four sub scores are calculated and presented as a percentage. Absenteeism = percent work time missed due to problem; Presenteeism = percent impairment while working due to problem; Work productivity= percent overall work impairment due to problem; Activity Impairment = percent activity Impairment due to problem). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.

The WPAI employment status questionnaire is a PRO consisting of 6 items that assess working status, specifically the impact of MS on absenteeism, presentism, work productivity loss and activity impairment over the past 7 days. Four sub scores are calculated and presented as a percentage. Absenteeism = percent work time missed due to problem; Presenteeism = percent impairment while working due to problem; Work productivity= percent overall work impairment due to problem; Activity Impairment = percent activity Impairment due to problem). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.

The SymptoMScreen comprises 12 distinct domains representing common MS symptoms: mobility, dexterity, vision, fatigue, cognition, bladder function, sensation, dizziness, spasticity, body pain, depression, and anxiety. Limitations associated with each symptom are rated on a 7-point Likert scale ranging from 0 ("not affected at all") to 6 ("total limitation; I am unable to perform most daily activities"). Domain scores are summed to generate a total score ranging from 0 to 72, with higher scores indicating greater symptom-related limitations.

The SymptoMScreen comprises 12 distinct domains representing common MS symptoms: mobility, dexterity, vision, fatigue, cognition, bladder function, sensation, dizziness, spasticity, body pain, depression, and anxiety. Limitations associated with each symptom are rated on a 7-point Likert scale ranging from 0 ("not affected at all") to 6 ("total limitation; I am unable to perform most daily activities"). Domain scores are summed to generate a total score ranging from 0 to 72, with higher scores indicating greater symptom-related limitations.

The MSIS-29 version 2 (MSIS-29v2) is a 29-item patient-reported outcome (PRO) measure designed to assess the physical and psychological impact of MS. The Physical Scale consists of 20 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw physical impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better health-related quality of life (HRQoL).

The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Physical Scale consists of 20 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw physical impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.

The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Psychological Scale consists of 9 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.

The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Psychological Scale consists of 9 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.