Long-term Follow-up of Fingolimod Phase II Study Patients

EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A negative change from baseline indicates improvement.

Disability progression is defined as: 1.5-point increase from baseline in participants with baseline EDSS score = 0.0; OR 1-point increase in EDSS from baseline in participants with baseline EDSS score of 1.0 to 5.0 inclusive; OR 0.5-point increase in EDSS from baseline in participants with baseline EDSS score >5.0.

EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A positive change from baseline indicates improvement.

The number of participants not using a wheelchair or being bedridden was assessed.

SPMS follows an initial relapsing-remitting course. Most people who are diagnosed with relapsing-remitting multiple sclerosis (RRMS) will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function (accumulation of disability) over time. Participants who were classified as SPMS were assessed.

First use of an ambulatory device was considered from EDSS 6.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 6.0.

First use of a wheelchair was considered from EDSS 7.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 7.0.

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Both the dominant and non-dominant hands are tested twice (two consecutive trials of the dominant hand, followed immediately by two consecutive trials of the non-dominant hand). The time limit per trial is 300 seconds. The right and left hand scores were the time in seconds it took to insert and remove 9 pegs ((the average scores from the four trials on the 9-HPT (the two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged)). A negative change from baseline indicates improvement.

The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. The PASAT is the last measure administered at each visit. It is presented on audio compact disc (CD) to control the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test result is the number of correct sums given (out of 60 possible). A positive change from baseline indicates improvement.

The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The patient is directed to one end of a clearly marked 25-foot (7.62 m) course and is instructed to walk 25 feet (7.62 meter) as quickly as possible, but safely. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. The test scores were the time in seconds it took to walk the 25 feet. A negative change from baseline indicates improvement.

MSFC is a composite measure encompassing information from the nine-hole peg test (arm dimension), timed 25 foot walk (leg dimension) and PASAT. The MSFC composite Z score was calculated as follows: (1) the average scores from the four trials on the 9-HPT (the two trials for each hand were averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals were averaged); (2) the average scores of two 25-Foot Timed Walk trials; (3) the number correct from the PASAT-3. The MSFC is based on the concept that scores for these three dimensions-arm, leg, and cognitive function are combined to create a single score (the MSFC) that can be used to detect change over time in a group of multiple sclerosis patients. This was done by creating Z-scores for each component of the MSFC, and averaging them to create an overall composite Z score.

Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI).

Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement.

Third ventricle diameter was assessed by MRI.

Third ventricle diameter was assessed by MRI. A negative change from baseline indicates improvement.

PVBC was assessed by MRI. A negative change from baseline indicates improvement.

The correlation between FTY treatment duration and disability progression outcomes was assessed. The number presented in the table is the Pearson correlation coefficient, r.