Observational Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JC Virus Antibody Negative Participants

Overall disease activity-free is defined as no relapses, no disability progression (RRMS), and absence of MRI disease activity (no gadolinium [gd])+ lesions, no new or enlarging T2-hyperintense lesions). A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. Sustained disability progression defined by at least a 1.0-point increase on the EDSS from a Baseline EDSS ≥1.0 that is sustained for 12 or 24 weeks, or at least a 1.5-point increase on the EDSS from a Baseline EDSS <1.0 that is sustained for 12 or 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10, with higher scores indicating more disability.

Clinical disease activity-free is defined as no sustained EDSS progression and no relapses at Month 36 and 48.

A clinical relapse is a new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.

A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. The ARR will be calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365.

Sustained improvement in disability is defined as participants with Baseline EDSS of at least 2.0 who experience a ≥1.0 decrease in EDSS that is sustained for 24 weeks.

Low-contrast visual acuity testing captures the minimum size at which individuals can perceive letters of a particular contrast level (shade of gray on white background). Using the low-contrast Sloan letter charts at 2.5% and 1.25% low contrast levels, participants will be asked to read each of the 2 charts at a 2-meter distance using a standardized testing protocol.

High contrast acuity testing is important to help determine the smallest letters a person can read on a standardized visual acuity chart or on a card held 14 - 20 feet away. A visual acuity test is a routine part of an eye examination.

SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best).

The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteeism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.

The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a participant-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a participant's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health.

Expanded Disability Status Scale (EDSS) is a method of quantifying disability in 8 Functional Systems (FS) and allows neurologists to assign a Functional System Score (FSS) in each of these. The FSS include pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. Each of the FSS is an ordinal clinical rating scale ranging from 0 to 5 or 6, with higher scores indicating more disability. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Each of the FSS and the EDSS are single-item scales and there is no composite or summed score.