Multiple Sclerosis, Relapsing Forms of Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, MS, RRMS, relapsing forms of multiple sclerosis, fingolimod, FTY720, Gilenya
Brief summary
This study collected follow-up data on approximately 90% of participants who were randomized and received one dose of study drug in FTY720D2201 (D2201). No study drug was given or required. Participants were required to be assessed at one or two visits, preferably at the original study site, but the option to be interviewed via phone or seen at home was provided. Information was gathered also on deceased participants. Assessments were performed only once within an 8 week period and included medical history, Multiple Sclerosis (MS) and Multiple Sclerosis Disease Modifying Therapy (MS DMT) history, Expanded Disability Status Scale (EDSS), Magnetic Resonance Imaging (MRI), and Multiple Sclerosis Functional Composite (MSFC).
Detailed description
This was a multicenter follow-up study of patients originally enrolled in the Phase 2 D2201 study. Patients did not receive any protocol specified treatment. The original D2201 study sites who agreed to participate in this study were required to locate their patients who were randomized in Study D2201 and asked them to return for a 10-year assessment, regardless of their current treatment status. Locating the patient may have required the use of search and advertising strategies to find those patients currently lost to follow-up, in accordance with local privacy legislation. Patients currently being followed within Study FTY720D2399 (NCT01201356) were asked to participate in Study FTY720D2201E2 and if patients gave consent, were enrolled concurrently in both studies.
Interventions
OTHERAssessments arm
Protocol required assessments not provided in standard of care
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed. * Randomized in study FTY720D2201 and received at least one dose of study drug.
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (BL) in Expanded Disability Status Scale (EDSS) | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With EDSS <4 or <6 | 10 years | 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. |
| Number of Participants Not Using a Wheelchair or Being Bedridden | 10 years | The number of participants not using a wheelchair or being bedridden was assessed. |
| Number of Participants Classified as Secondary Progressive MS (SPMS) | 10 years | 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. |
| Percentage of Participants With First Use of an Ambulatory Device | 10 years | 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. |
| Percentage of Participants With First Use of a Wheelchair | 10 years | First use of a wheelchair was considered from EDSS 7.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 7.0. |
| Change From Baseline in Multiple Sclerosis Fuctional Composite (MSFC) Component: Nine Hole Peg Test (9-HPT) | baseline from core study, CFTY720D2201 (NCT00333138), 10 years | 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. |
| Change From Baseline in MSFC Component: Paced Auditory Serial Addition Test (PASAT) Score | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 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. |
| Number of Participants With Disability Progression | 10 Years | 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. |
| Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z Score | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 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 | 10 years | Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI). |
| Change From Baseline in Total Volume of T2 Lesion | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement. |
| Third Ventricle Diameter | 10 years | Third ventricle diameter was assessed by MRI. |
| Change From Baseline in Third Ventricle Diameter | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | Third ventricle diameter was assessed by MRI. A negative change from baseline indicates improvement. |
| Percentage Brain Volume Change (PBVC) | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | PVBC was assessed by MRI. A negative change from baseline indicates improvement. |
| Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | 10 years | The correlation between FTY treatment duration and disability progression outcomes was assessed. The number presented in the table is the Pearson correlation coefficient, r. |
| Change From Baseline in MSFC Component: Timed 25-foot Walk Test Score | baseline from core study (CFTY720D2201 (NCT00333138)), 10 years | 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. |
Countries
Canada, Denmark, France, Germany, Italy, Poland, Portugal, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
This extension study was a multicenter follow-up study of participants who enrolled in FTY720D2201 (NCT02307838). Although participants in this study did not receive study treatment, the participant flow is based on the treatments receive in FTY720D2201.
Pre-assignment details
A total of 177 participants were enrolled into the study. However, 2 participants were erroneously enrolled into the study because they did not meet the inclusion criteria. Therefore, they were not included in any analyses, and as such, the participant flow is based on 175 participants.
Participants by arm
| Arm | Count |
|---|---|
| Continuous Participants had exposure to FTY720 (study drug or commercially) for at least 8 years. | 104 |
| Non-continuous Participants had exposure to FTY720 (study drug or commercially) for less than 8 years. | 16 |
| Non-continuous: Other DMTs Participants had exposure to FTY720 (study drug or commercially) for less than 8 years. Also, participants were exposed to high-efficacy DMTs for less than 2 years. This group may have included participants who did not report any DMTs at all. | 55 |
| Total | 175 |
Baseline characteristics
| Characteristic | Continuous | Non-continuous | Non-continuous: Other DMTs | Total |
|---|---|---|---|---|
| Age, Continuous | 37.4 Years STANDARD_DEVIATION 8.47 | 31.9 Years STANDARD_DEVIATION 9.05 | 38.9 Years STANDARD_DEVIATION 10.49 | 37.4 Years STANDARD_DEVIATION 9.34 |
| Sex: Female, Male Female | 63 Participants | 13 Participants | 41 Participants | 117 Participants |
| Sex: Female, Male Male | 41 Participants | 3 Participants | 14 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 104 | 0 / 16 | 1 / 55 |
| serious Total, serious adverse events | 0 / 104 | 0 / 16 | 0 / 55 |
Outcome results
Primary
Change From Baseline (BL) in Expanded Disability Status Scale (EDSS)
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.
Time frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years
Population: The full analysis set (FAS) included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Change From Baseline (BL) in Expanded Disability Status Scale (EDSS) | 0.58 score on a scale | Standard Error 0.154 |
| Non-continuous | Change From Baseline (BL) in Expanded Disability Status Scale (EDSS) | 1.17 score on a scale | Standard Error 0.185 |
p-value: 0.015595% CI: [-1.07, -0.11]ANCOVA
Secondary
Change From Baseline in MSFC Component: Paced Auditory Serial Addition Test (PASAT) Score
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.
Time frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years
Population: The FAS was considered for the analysis. Only participants with both baseline and 10 year measurements were analyzed. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Change From Baseline in MSFC Component: Paced Auditory Serial Addition Test (PASAT) Score | 0.54 score on a scale | Standard Deviation 8.273 |
| Non-continuous | Change From Baseline in MSFC Component: Paced Auditory Serial Addition Test (PASAT) Score | -5.39 score on a scale | Standard Deviation 12.428 |
Secondary
Change From Baseline in MSFC Component: Timed 25-foot Walk Test Score
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.
Time frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years
Population: The FAS was considered for the analysis. Only participants with both baseline and 10 year measurements were analyzed. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Change From Baseline in MSFC Component: Timed 25-foot Walk Test Score | 1.32 score on a scale | Standard Deviation 11.632 |
| Non-continuous | Change From Baseline in MSFC Component: Timed 25-foot Walk Test Score | 3.89 score on a scale | Standard Deviation 16.07 |
Secondary
Change From Baseline in Multiple Sclerosis Fuctional Composite (MSFC) Component: Nine Hole Peg Test (9-HPT)
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.
Time frame: baseline from core study, CFTY720D2201 (NCT00333138), 10 years
Population: The full analysis set (FAS) included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Change From Baseline in Multiple Sclerosis Fuctional Composite (MSFC) Component: Nine Hole Peg Test (9-HPT) | 2.29 seconds | Standard Deviation 5.772 |
| Non-continuous | Change From Baseline in Multiple Sclerosis Fuctional Composite (MSFC) Component: Nine Hole Peg Test (9-HPT) | 5.06 seconds | Standard Deviation 14.523 |
Secondary
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z Score
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.
Time frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years
Population: The FAS was considered for the analysis. Only participants with both baseline measurements for each MSFC component and 10 year measurements were analyzed. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or MRI within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z Score | -0.11 Z score | Standard Deviation 0.536 |
| Non-continuous | Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z Score | -0.60 Z score | Standard Deviation 1.297 |
Secondary
Change From Baseline in Third Ventricle Diameter
Third ventricle diameter was assessed by MRI. A negative change from baseline indicates improvement.
Time frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years
Population: The FAS was considered for analysis. Only participants who had both baseline and 10 year measurements were analyzed. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or MRI within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Change From Baseline in Third Ventricle Diameter | 0.80 mm | Standard Deviation 0.848 |
| Non-continuous | Change From Baseline in Third Ventricle Diameter | 0.92 mm | Standard Deviation 0.784 |
Secondary
Change From Baseline in Total Volume of T2 Lesion
Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement.
Time frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years
Population: The FAS was considered for the analysis. Only participants from the FAS who had both baseline and 10 years measurements were included in the analysis. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or MRI within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Change From Baseline in Total Volume of T2 Lesion | 1031.7 mm^3 | Standard Deviation 3725.8 |
| Non-continuous | Change From Baseline in Total Volume of T2 Lesion | 3636.7 mm^3 | Standard Deviation 5259.84 |
Secondary
Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters
The correlation between FTY treatment duration and disability progression outcomes was assessed. The number presented in the table is the Pearson correlation coefficient, r.
Time frame: 10 years
Population: The FAS was considered for the analysis. Only participants who had 10 year correlation measurements were analyzed. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or MRI within study FTY720D2201.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | EDSS score at year 10 (n=101,71) | -0.12 Pearson correlation coeffcient |
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to 1st use of a cane/crutch/walker (n=13,15) | 0.35 Pearson correlation coeffcient |
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first documenting EDSS of >= 6.0 (n=12,11) | 0.27 Pearson correlation coeffcient |
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first use of a wheelchair (n=5,12) | 0.57 Pearson correlation coeffcient |
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first becoming bedridden (n=0,0) | NA Pearson correlation coeffcient |
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first SPMS classification (n=10,16) | 0.38 Pearson correlation coeffcient |
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Year 10 PASAT-3 score (n=93,56) | -0.14 Pearson correlation coeffcient |
| Continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Year 10 PASAT-3 score change from BL (n=93,56) | 0.01 Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Year 10 PASAT-3 score change from BL (n=93,56) | 0.39 Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | EDSS score at year 10 (n=101,71) | -0.09 Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first becoming bedridden (n=0,0) | NA Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to 1st use of a cane/crutch/walker (n=13,15) | 0.11 Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Year 10 PASAT-3 score (n=93,56) | 0.28 Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first documenting EDSS of >= 6.0 (n=12,11) | 0.00 Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first SPMS classification (n=10,16) | 0.32 Pearson correlation coeffcient |
| Non-continuous | Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters | Time to first use of a wheelchair (n=5,12) | 0.33 Pearson correlation coeffcient |
Secondary
Number of Participants Classified as Secondary Progressive MS (SPMS)
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.
Time frame: 10 years
Population: The full analysis set (FAS) included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous | Number of Participants Classified as Secondary Progressive MS (SPMS) | 10 Participants |
| Non-continuous | Number of Participants Classified as Secondary Progressive MS (SPMS) | 2 Participants |
| Non-continuous: Other DMTs | Number of Participants Classified as Secondary Progressive MS (SPMS) | 14 Participants |
Secondary
Number of Participants Not Using a Wheelchair or Being Bedridden
The number of participants not using a wheelchair or being bedridden was assessed.
Time frame: 10 years
Population: The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous | Number of Participants Not Using a Wheelchair or Being Bedridden | 99 Participants |
| Non-continuous | Number of Participants Not Using a Wheelchair or Being Bedridden | 13 Participants |
| Non-continuous: Other DMTs | Number of Participants Not Using a Wheelchair or Being Bedridden | 46 Participants |
Secondary
Number of Participants With Disability Progression
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.
Time frame: 10 Years
Population: The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous | Number of Participants With Disability Progression | 35 Participants |
| Non-continuous | Number of Participants With Disability Progression | 8 Participants |
| Non-continuous: Other DMTs | Number of Participants With Disability Progression | 29 Participants |
Secondary
Number of Participants With EDSS <4 or <6
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.
Time frame: 10 years
Population: The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Continuous | Number of Participants With EDSS <4 or <6 | EDSS <4 | 78 Participants |
| Continuous | Number of Participants With EDSS <4 or <6 | EDSS <6 | 90 Participants |
| Non-continuous | Number of Participants With EDSS <4 or <6 | EDSS <4 | 10 Participants |
| Non-continuous | Number of Participants With EDSS <4 or <6 | EDSS <6 | 13 Participants |
| Non-continuous: Other DMTs | Number of Participants With EDSS <4 or <6 | EDSS <4 | 31 Participants |
| Non-continuous: Other DMTs | Number of Participants With EDSS <4 or <6 | EDSS <6 | 41 Participants |
Secondary
Percentage Brain Volume Change (PBVC)
PVBC was assessed by MRI. A negative change from baseline indicates improvement.
Time frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years
Population: The FAS was considered for the analysis. Only participants with both baseline and 10 year measurements were analyzed. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or MRI within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Percentage Brain Volume Change (PBVC) | -9.28 Percent change | Standard Deviation 4.412 |
| Non-continuous | Percentage Brain Volume Change (PBVC) | -9.87 Percent change | Standard Deviation 2.909 |
Secondary
Percentage of Participants With First Use of an Ambulatory Device
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.
Time frame: 10 years
Population: The FAS was considered for the analysis. Only participants with evaluable data were included in the analysis. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous | Percentage of Participants With First Use of an Ambulatory Device | 12.4 Percentage of participants |
| Non-continuous | Percentage of Participants With First Use of an Ambulatory Device | 17.6 Percentage of participants |
Secondary
Percentage of Participants With First Use of a Wheelchair
First use of a wheelchair was considered from EDSS 7.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 7.0.
Time frame: 10 years
Population: The full analysis set (FAS) included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or magnetic resonance imaging (MRI) within study FTY720D2201.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous | Percentage of Participants With First Use of a Wheelchair | 4.9 Percentage of participants |
| Non-continuous | Percentage of Participants With First Use of a Wheelchair | 16.9 Percentage of participants |
Secondary
Third Ventricle Diameter
Third ventricle diameter was assessed by MRI.
Time frame: 10 years
Population: The FAS was considered for the analysis. Only participants with 10 year measurements were analyzed. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or MRI within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Third Ventricle Diameter | 5.28 mm | Standard Deviation 2.047 |
| Non-continuous | Third Ventricle Diameter | 5.57 mm | Standard Deviation 2.648 |
Secondary
Total Volume in T2 Lesion
Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI).
Time frame: 10 years
Population: The FAS was considered for the analysis. Only participants with measurements at 10 years were included in the analysis. The FAS included all participants who received at least one dose of study drug during FTY720D2201 and had at least one pre-treatment assessment in EDSS or MRI within study FTY720D2201.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous | Total Volume in T2 Lesion | 8685.4 mm^3 | Standard Deviation 7743.05 |
| Non-continuous | Total Volume in T2 Lesion | 11279.0 mm^3 | Standard Deviation 12570.11 |