Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Fingolimod,cytokine,chemokine,RRMS
Brief summary
The main purpose of this study was to measure the serum levels of cytokines and chemokines that are known to increase during multiple sclerosis relapses. Cytokines are a broad and loose category of small proteins that are important in cell signaling. The second purpose of the study was to test the cytokine/chemokine changes measured in the 3rd and 6th months on the efficacy parameters.
Interventions
66 relapsing remitting MS (RRMS) patients were recruited. Patients who met all inclusion and none of the exclusion criteria were treated by Fingolimod 0.5 mg.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A 6-month, multicenter, prospective, interventional, single arm, open label study investigating the effects of fingolimod administered according to local label recommendations on Cytokine and Chemokine Levels in Relapsing Remitting Multiple Sclerosis Patients
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Written informed consent must be obtained before the beginning of te study 2. Nonresponder RRMS patients 3. Last relapse of the patient should be at least 2 months before study entry. 4. Last interferon or glatiramer acetate dose of the patient should be at least 1 month before study entry. Key
Exclusion criteria
1. Patients with secondary progressive MS. 2. Patients with known contraindications for fingolimod treatment. 3. Other coexistent autoimmune diseases 4. Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | Baseline | Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis. |
| Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | Baseline | Blood samples were taken at baseline and measurements were performed before treatment of fingolimod. |
| Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | Baseline | baseline peripheral blood flow cytometric analysis in study participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | Baseline, month 3, month 6 | Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits |
| Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Baseline, Month 3, Month 6 | Peripheral blood chemokine cytokine levels measured by flow cytometry in healthy controls at baseline and in RRMS patients between visits during fingolimod treatment |
| Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Baseline, Month 3, Month 6 | Peripheral blood chemokine cytokine levels measured by flow cytometry during fingolimod treatment in healthy controls at baseline and in RRMS patients between visits |
| Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Baseline, Month 3, Month 6 | Peripheral blood chemokine cytokine levels measured by flow cytometry at baseline and between visits during fingolimod treatment. Absolute counts of the cells were calculated according to the absolute lymphocyte counts and the percentages of cells. This allowed for a clear determination of cell counts and thus increased the reliability of the results. |
Countries
Turkey (Türkiye)
Participant flow
Pre-assignment details
60 healthy controls and 66 Relapsing-remitting multiple sclerosis (RRMS) patients were enrolled in the study. The healthy volunteers had only Visit 1 (Day 0). Fingolimod 0.5 mg capsule once daily was given on the same day to RRMS patients. Patients were treated for 6 months with 2 additional visits, Visit 2 and Visit 3.
Participants by arm
| Arm | Count |
|---|---|
| FTY720 Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. | 66 |
| Healthy Volunteers The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements | 60 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | FTY720 | Healthy Volunteers | Total |
|---|---|---|---|
| Age, Continuous | 35.75 Years STANDARD_DEVIATION 8.2 | 34.73 Years STANDARD_DEVIATION 9.62 | 35.27 Years STANDARD_DEVIATION 8.89 |
| Race/Ethnicity, Customized Turkish | 66 Participants | 60 Participants | 126 Participants |
| Sex: Female, Male Female | 46 Participants | 40 Participants | 86 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 66 |
| other Total, other adverse events | 7 / 66 | 7 / 66 |
| serious Total, serious adverse events | 3 / 66 | 3 / 66 |
Outcome results
Primary
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
baseline peripheral blood flow cytometric analysis in study participants
Time frame: Baseline
Population: Analysis was done in the healthy volunteers and RRMS patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | NK abs | 281.33 absolute cell count | Standard Error 39.106 |
| Healthy Controls | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | Hi CD16CD56 abs | 26.64 absolute cell count | Standard Error 4.399 |
| Healthy Controls | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | CD19 abs | 311.63 absolute cell count | Standard Error 57.592 |
| Healthy Controls | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | CD4CD25 (CD3 gate) | 26.08 absolute cell count | Standard Error 3.159 |
| Healthy Controls | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | NKT abs | 135.86 absolute cell count | Standard Error 16.627 |
| Healthy Controls | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | Hi CD4CD25 (CD3 gate) | 2.83 absolute cell count | Standard Error 0.383 |
| Healthy Controls | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | CD3 abs | 2048.14 absolute cell count | Standard Error 263.209 |
| FTY720 | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | Hi CD4CD25 (CD3 gate) | 3.33 absolute cell count | Standard Error 0.253 |
| FTY720 | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | CD3 abs | 1610.94 absolute cell count | Standard Error 126.071 |
| FTY720 | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | CD19 abs | 327.63 absolute cell count | Standard Error 44.421 |
| FTY720 | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | NK abs | 623.57 absolute cell count | Standard Error 394.837 |
| FTY720 | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | NKT abs | 104.36 absolute cell count | Standard Error 15.08 |
| FTY720 | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | Hi CD16CD56 abs | 20.44 absolute cell count | Standard Error 3.506 |
| FTY720 | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | CD4CD25 (CD3 gate) | 27.08 absolute cell count | Standard Error 1.251 |
Comparison: CD3 absp-value: 0.256Wilcoxon (Mann-Whitney)
Comparison: CD19 absp-value: 0.587Wilcoxon (Mann-Whitney)
Comparison: NK absp-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: NKT absp-value: 0.096Wilcoxon (Mann-Whitney)
Comparison: Hi CD16CD56 absp-value: 0.27Wilcoxon (Mann-Whitney)
Comparison: CD4CD25p-value: 0.902Wilcoxon (Mann-Whitney)
Comparison: Hi CD4CD25p-value: 0.283Wilcoxon (Mann-Whitney)
Primary
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
Blood samples were taken at baseline and measurements were performed before treatment of fingolimod.
Time frame: Baseline
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CXCL13 | 110.8 pg/ml | Standard Error 22.3 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | VLA4 | 1.17 pg/ml | Standard Error 0.396 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL8 | 3.25 pg/ml | Standard Error 0.47 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CXCL10=IP-10 (CXCR3 ligand) | 16.09 pg/ml | Standard Error 1.76 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL-17A | 1.15 pg/ml | Standard Error 0.03 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CCL2=MCP-1 | 52.88 pg/ml | Standard Error 4.281 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL13 | 0.49 pg/ml | Standard Error 0.331 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL4 | 2.02 pg/ml | Standard Error 0.077 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL6 | 0.88 pg/ml | Standard Error 0.324 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | TNF alpha | 1.1 pg/ml | Standard Error 0.195 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL23 | 1.29 pg/ml | Standard Error 0.552 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL22 | 22.36 pg/ml | Standard Error 0.581 |
| Healthy Controls | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CCL5 (RANTES) | 212.26 pg/ml | Standard Error 22.48 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL22 | 22.41 pg/ml | Standard Error 0.547 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CCL5 (RANTES) | 404.31 pg/ml | Standard Error 55.189 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL-17A | 1.06 pg/ml | Standard Error 0.029 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CXCL13 | 139.68 pg/ml | Standard Error 46.631 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL6 | 66.53 pg/ml | Standard Error 65.411 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL8 | 3.57 pg/ml | Standard Error 0.553 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL13 | 0.3 pg/ml | Standard Error 0.15 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL23 | 3.04 pg/ml | Standard Error 0.924 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | VLA4 | 0.58 pg/ml | Standard Error 0.201 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CXCL10=IP-10 (CXCR3 ligand) | 18.18 pg/ml | Standard Error 2.405 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | CCL2=MCP-1 | 62.89 pg/ml | Standard Error 8.42 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | IL4 | 2.36 pg/ml | Standard Error 0.149 |
| FTY720 | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | TNF alpha | 1.06 pg/ml | Standard Error 0.1 |
Comparison: CCL5=RANTESp-value: 0Wilcoxon (Mann-Whitney)
Comparison: IL17Ap-value: 0.035Wilcoxon (Mann-Whitney)
Comparison: CXCL13p-value: 0.911Wilcoxon (Mann-Whitney)
Comparison: IL6p-value: 1Wilcoxon (Mann-Whitney)
Comparison: IL8p-value: 0.934Wilcoxon (Mann-Whitney)
Comparison: IL13p-value: 0.727Wilcoxon (Mann-Whitney)
Comparison: IL23p-value: 0.179Wilcoxon (Mann-Whitney)
Comparison: VLA4p-value: 0.208Wilcoxon (Mann-Whitney)
Comparison: CXCL10=IP-10 (CXCR3 ligand)p-value: 0.73Wilcoxon (Mann-Whitney)
Comparison: CCL2=MCP-1p-value: 0.725Wilcoxon (Mann-Whitney)
Comparison: IL4p-value: 0.057Wilcoxon (Mann-Whitney)
Comparison: TNF alphap-value: 0.724Wilcoxon (Mann-Whitney)
Comparison: IL22p-value: 0.662Wilcoxon (Mann-Whitney)
Primary
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis.
Time frame: Baseline
Population: Analysis was done in the healthy volunteers and RRMS patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL17+ (in CD4+CD25+) | 2.35 Percent of cells | Standard Error 0.264 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | Hi CD16CD56 % | 1.05 Percent of cells | Standard Error 0.183 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL10+ (in CD4+) | 1.64 Percent of cells | Standard Error 0.33 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD8 % (CD3 gate) | 35.11 Percent of cells | Standard Error 2.305 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL4+ (in CD4+) | 1.44 Percent of cells | Standard Error 0.294 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD19 % | 11.57 Percent of cells | Standard Error 1.018 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4-CD8-IL4+ (in CD4-CD8-) | 1.31 Percent of cells | Standard Error 0.31 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IFNg+ (in CD4+) | 7.42 Percent of cells | Standard Error 1.994 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL10+ (in CD8+) | 0.52 Percent of cells | Standard Error 0.089 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD4 % (Lymphogate) | 41.19 Percent of cells | Standard Error 2.483 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL4+ % (in CD8+) | 5.64 Percent of cells | Standard Error 3.74 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL17+ (in CD4+) | 1.23 Percent of cells | Standard Error 0.173 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL10+ (in CD4+CD25+) | 2.57 Percent of cells | Standard Error 0.228 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | NKT % | 5.65 Percent of cells | Standard Error 0.855 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL4+ (in CD4+CD25+) | 1.88 Percent of cells | Standard Error 0.34 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IFNg+ (in CD8+) | 16.45 Percent of cells | Standard Error 3.896 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+TNFa+ (in CD4+) | 46.86 Percent of cells | Standard Error 4.892 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD8 % (Lymphogate) | 23.23 Percent of cells | Standard Error 2.175 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL9+ (in CD4+) | 0.22 Percent of cells | Standard Error 0.109 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL17+ (in CD8+) | 1.71 Percent of cells | Standard Error 0.636 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+TNFa+ (in CD8+) | 35 Percent of cells | Standard Error 4.876 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | NK % | 11.04 Percent of cells | Standard Error 1.328 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL9+ (in CD8+) | 0.14 Percent of cells | Standard Error 0.087 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IFNg+ (in CD4+CD25+) | 7.1 Percent of cells | Standard Error 1.896 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | TNFa+ (in CD4+CD25+) | 52.82 Percent of cells | Standard Error 5.019 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD4 % (CD3 gate) | 57.38 Percent of cells | Standard Error 2.722 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL9+ (in CD4+CD25+) | 5.06 Percent of cells | Standard Error 4.497 |
| Healthy Controls | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3 % | 76.52 Percent of cells | Standard Error 1.494 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL9+ (in CD4+CD25+) | 0.59 Percent of cells | Standard Error 0.221 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3 % | 71.92 Percent of cells | Standard Error 1.134 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD19 % | 13.72 Percent of cells | Standard Error 1.336 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | NK % | 10.17 Percent of cells | Standard Error 1.169 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | NKT % | 5.19 Percent of cells | Standard Error 0.766 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | Hi CD16CD56 % | 0.93 Percent of cells | Standard Error 0.145 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD4 % (Lymphogate) | 44.91 Percent of cells | Standard Error 1.321 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD8 % (Lymphogate) | 22.91 Percent of cells | Standard Error 1.188 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD4 % (CD3 gate) | 62.99 Percent of cells | Standard Error 1.446 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD3CD8 % (CD3 gate) | 31.20 Percent of cells | Standard Error 1.351 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IFNg+ (in CD4+) | 3.61 Percent of cells | Standard Error 1.037 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL17+ (in CD4+) | 1.27 Percent of cells | Standard Error 0.298 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IFNg+ (in CD8+) | 5.47 Percent of cells | Standard Error 2.463 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL17+ (in CD8+) | 4.20 Percent of cells | Standard Error 0.923 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IFNg+ (in CD4+CD25+) | 1.98 Percent of cells | Standard Error 0.469 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL17+ (in CD4+CD25+) | 2.06 Percent of cells | Standard Error 0.41 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL10+ (in CD4+) | 0.72 Percent of cells | Standard Error 0.196 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL4+ (in CD4+) | 0.96 Percent of cells | Standard Error 0.41 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4-CD8-IL4+ (in CD4-CD8-) | 2.62 Percent of cells | Standard Error 1.125 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL10+ (in CD8+) | 0.31 Percent of cells | Standard Error 0.096 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL4+ % (in CD8+) | 1.87 Percent of cells | Standard Error 0.538 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL10+ (in CD4+CD25+) | 1.81 Percent of cells | Standard Error 0.464 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | IL4+ (in CD4+CD25+) | 0.50 Percent of cells | Standard Error 0.105 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+TNFa+ (in CD4+) | 23.72 Percent of cells | Standard Error 4.707 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD4+IL9+ (in CD4+) | 0.54 Percent of cells | Standard Error 0.163 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+TNFa+ (in CD8+) | 11.78 Percent of cells | Standard Error 2.679 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | CD8+IL9+ (in CD8+) | 0.90 Percent of cells | Standard Error 0.245 |
| FTY720 | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | TNFa+ (in CD4+CD25+) | 23.29 Percent of cells | Standard Error 4.43 |
Comparison: CD3 %p-value: 0.017Wilcoxon (Mann-Whitney)
Comparison: CD19 %p-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: NK %p-value: 0.657Wilcoxon (Mann-Whitney)
Comparison: NKT %p-value: 0.439Wilcoxon (Mann-Whitney)
Comparison: Hi CD16CD56 %p-value: 0.449Wilcoxon (Mann-Whitney)
Comparison: CD3CD4p-value: 0.356Wilcoxon (Mann-Whitney)
Comparison: CD3CD8p-value: 0.787Wilcoxon (Mann-Whitney)
Comparison: CD3CD4p-value: 0.121Wilcoxon (Mann-Whitney)
Comparison: CD3CD8p-value: 0.209Wilcoxon (Mann-Whitney)
Comparison: CD4+IFNg+ (in CD4+)p-value: 0.069Wilcoxon (Mann-Whitney)
Comparison: CD4+IL17+ (in CD4+)p-value: 0.402Wilcoxon (Mann-Whitney)
Comparison: CD8+IFNg+ (in CD8+)p-value: 0.017Wilcoxon (Mann-Whitney)
Comparison: CD8+IL17+ (in CD8+)p-value: 0.017Wilcoxon (Mann-Whitney)
Comparison: IFNg+ (in CD4+CD25+)p-value: 0.026Wilcoxon (Mann-Whitney)
Comparison: IL17+ (in CD4+CD25+)p-value: 0.168Wilcoxon (Mann-Whitney)
Comparison: CD4+IL10+ (in CD4+)p-value: 0.004Wilcoxon (Mann-Whitney)
Comparison: CD4+IL4+ (in CD4+)p-value: 0.013Wilcoxon (Mann-Whitney)
Comparison: CD4-CD8-IL4+ (in CD4-CD8-)p-value: 0.171Wilcoxon (Mann-Whitney)
Comparison: CD8+IL10+ (in CD8+)p-value: 0.013Wilcoxon (Mann-Whitney)
Comparison: CD8+IL4+ (in CD8+)p-value: 0.013Wilcoxon (Mann-Whitney)
Comparison: IL10+ (in CD4+CD25+)p-value: 0.007Wilcoxon (Mann-Whitney)
Comparison: IL4+ (in CD4+CD25+)p-value: 0.001Wilcoxon (Mann-Whitney)
Comparison: CD4+TNFa+ (in CD4+)p-value: 0.002Wilcoxon (Mann-Whitney)
Comparison: CD4+IL9+ (in CD4+)p-value: 0.107Wilcoxon (Mann-Whitney)
Comparison: CD8+TNFa+ (in CD8+)p-value: 0Wilcoxon (Mann-Whitney)
Comparison: CD8+IL9+ (in CD8+)p-value: 0.022Wilcoxon (Mann-Whitney)
Comparison: TNFa+ (in CD4+CD25+)p-value: 0.001Wilcoxon (Mann-Whitney)
Comparison: IL9+ (in CD4+CD25+)p-value: 0.127Wilcoxon (Mann-Whitney)
Secondary
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Peripheral blood chemokine cytokine levels measured by flow cytometry at baseline and between visits during fingolimod treatment. Absolute counts of the cells were calculated according to the absolute lymphocyte counts and the percentages of cells. This allowed for a clear determination of cell counts and thus increased the reliability of the results.
Time frame: Baseline, Month 3, Month 6
Population: Intent to treat. Data analyzed in RRMS patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL10+ (in CD4+) | 1.64 absolute cell count | Standard Error 0.33 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL17+ (in CD4+) | 1.23 absolute cell count | Standard Error 0.173 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+TNFa+ (in CD8+) | 35 absolute cell count | Standard Error 4.876 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL17+ (in CD4+CD25+) | 2.35 absolute cell count | Standard Error 0.264 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IFNg+ (in CD4+CD25+) | 7.1 absolute cell count | Standard Error 1.896 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IFNg+ (in CD8+) | 16.45 absolute cell count | Standard Error 3.896 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (Lymphogate) | 23.23 absolute cell count | Standard Error 2.175 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL17+ (in CD8+) | 1.71 absolute cell count | Standard Error 0.636 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | TNFa+ (in CD4+CD25+) | 52.82 absolute cell count | Standard Error 0.019 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL9+ (in CD4+) | 0.22 absolute cell count | Standard Error 0.109 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+TNFa+ (in CD4+) | 46.86 absolute cell count | Standard Error 4.892 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (CD3 gate) | 57.38 absolute cell count | Standard Error 2.722 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (Lymphogate) | 41.19 absolute cell count | Standard Error 2.483 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL4+ (in CD4+CD25+) | 1.88 absolute cell count | Standard Error 0.34 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL10+ (in CD4+CD25+) | 2.57 absolute cell count | Standard Error 0.228 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (CD3 gate) | 35.11 absolute cell count | Standard Error 2.305 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL9+ (in CD4+CD25+) | 5.06 absolute cell count | Standard Error 4.497 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL10+ (in CD8+) | 0.52 absolute cell count | Standard Error 0.089 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4-CD8-IL4+ (in CD4-CD8-) | 1.31 absolute cell count | Standard Error 0.31 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IFNg+ (in CD4+) | 7.42 absolute cell count | Standard Error 1.994 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL9+ (in CD8+) | 0.14 absolute cell count | Standard Error 0.087 |
| Healthy Controls | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL4+ (in CD4+) | 1.44 absolute cell count | Standard Error 2.94 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL9+ (in CD4+) | 0.54 absolute cell count | Standard Error 0.163 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (Lymphogate) | 44.91 absolute cell count | Standard Error 1.321 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (Lymphogate) | 22.91 absolute cell count | Standard Error 1.188 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (CD3 gate) | 62.99 absolute cell count | Standard Error 1.446 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (CD3 gate) | 31.2 absolute cell count | Standard Error 1.351 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IFNg+ (in CD4+) | 3.61 absolute cell count | Standard Error 1.037 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL17+ (in CD4+) | 1.27 absolute cell count | Standard Error 0.298 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IFNg+ (in CD8+) | 5.47 absolute cell count | Standard Error 2.463 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL17+ (in CD8+) | 4.2 absolute cell count | Standard Error 0.923 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IFNg+ (in CD4+CD25+) | 1.98 absolute cell count | Standard Error 0.469 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL17+ (in CD4+CD25+) | 2.06 absolute cell count | Standard Error 0.41 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL10+ (in CD4+) | 0.72 absolute cell count | Standard Error 0.196 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL4+ (in CD4+) | 0.96 absolute cell count | Standard Error 0.41 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4-CD8-IL4+ (in CD4-CD8-) | 2.62 absolute cell count | Standard Error 1.125 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL10+ (in CD8+) | 0.31 absolute cell count | Standard Error 0.096 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL10+ (in CD4+CD25+) | 1.81 absolute cell count | Standard Error 0.464 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL4+ (in CD4+CD25+) | 0.5 absolute cell count | Standard Error 0.105 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+TNFa+ (in CD4+) | 23.72 absolute cell count | Standard Error 4.707 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+TNFa+ (in CD8+) | 11.78 absolute cell count | Standard Error 2.679 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL9+ (in CD8+) | 0.9 absolute cell count | Standard Error 0.245 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | TNFa+ (in CD4+CD25+) | 23.29 absolute cell count | Standard Error 4.43 |
| FTY720 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL9+ (in CD4+CD25+) | 0.59 absolute cell count | Standard Error 0.221 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL4+ (in CD4+) | 1.45 absolute cell count | Standard Error 0.294 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (CD3 gate) | 59.52 absolute cell count | Standard Error 2.534 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL10+ (in CD4+) | 1.51 absolute cell count | Standard Error 0.422 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+TNFa+ (in CD4+) | 29.45 absolute cell count | Standard Error 5.681 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL10+ (in CD8+) | 0.25 absolute cell count | Standard Error 0.107 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (Lymphogate) | 32.93 absolute cell count | Standard Error 1.967 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IFNg+ (in CD4+) | 7.85 absolute cell count | Standard Error 2.197 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL9+ (in CD4+) | 0.4 absolute cell count | Standard Error 0.098 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL9+ (in CD8+) | 0.13 absolute cell count | Standard Error 0.061 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IFNg+ (in CD8+) | 5.73 absolute cell count | Standard Error 1.968 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+TNFa+ (in CD8+) | 20.93 absolute cell count | Standard Error 5.361 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL17+ (in CD8+) | 9.22 absolute cell count | Standard Error 3.105 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL9+ (in CD4+CD25+) | 0.72 absolute cell count | Standard Error 0.213 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL10+ (in CD4+CD25+) | 2.88 absolute cell count | Standard Error 0.471 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4-CD8-IL4+ (in CD4-CD8-) | 1.77 absolute cell count | Standard Error 0.267 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IFNg+ (in CD4+CD25+) | 7.07 absolute cell count | Standard Error 1.719 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (CD3 gate) | 23.26 absolute cell count | Standard Error 2.726 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL17+ (in CD4+) | 1.26 absolute cell count | Standard Error 0.224 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (Lymphogate) | 13.64 absolute cell count | Standard Error 1.712 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL17+ (in CD4+CD25+) | 1.85 absolute cell count | Standard Error 0.31 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | TNFa+ (in CD4+CD25+) | 30.39 absolute cell count | Standard Error 5.391 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL4+ (in CD4+CD25+) | 1.22 absolute cell count | Standard Error 0.224 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IFNg+ (in CD4+) | 13.97 absolute cell count | Standard Error 2.972 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL10+ (in CD4+) | 2.14 absolute cell count | Standard Error 0.486 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL4+ (in CD4+) | 2.32 absolute cell count | Standard Error 0.43 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (CD3 gate) | 59.66 absolute cell count | Standard Error 2.642 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL9+ (in CD8+) | 0.14 absolute cell count | Standard Error 0.068 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4-CD8-IL4+ (in CD4-CD8-) | 2.64 absolute cell count | Standard Error 0.909 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL9+ (in CD4+) | 0.47 absolute cell count | Standard Error 0.143 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL10+ (in CD8+) | 0.67 absolute cell count | Standard Error 0.169 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (CD3 gate) | 24 absolute cell count | Standard Error 2.788 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL10+ (in CD4+CD25+) | 4.03 absolute cell count | Standard Error 0.793 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL4+ (in CD4+CD25+) | 1.49 absolute cell count | Standard Error 0.316 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD8 (Lymphogate) | 32.22 absolute cell count | Standard Error 2.169 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | TNFa+ (in CD4+CD25+) | 40.4 absolute cell count | Standard Error 4.907 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+TNFa+ (in CD4+) | 49.96 absolute cell count | Standard Error 5.832 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3CD4 (Lymphogate) | 13.9 absolute cell count | Standard Error 1.522 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IFNg+ (in CD8+) | 14.7 absolute cell count | Standard Error 3.834 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL17+ (in CD8+) | 2.23 absolute cell count | Standard Error 0.505 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4+IL17+ (in CD4+) | 2.02 absolute cell count | Standard Error 0.342 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+TNFa+ (in CD8+) | 41.53 absolute cell count | Standard Error 6.18 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IFNg+ (in CD4+CD25+) | 9.31 absolute cell count | Standard Error 1.699 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL17+ (in CD4+CD25+) | 2.7 absolute cell count | Standard Error 0.451 |
| Visit 3 | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | IL9+ (in CD4+CD25+) | 1.3 absolute cell count | Standard Error 0.507 |
Secondary
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Peripheral blood chemokine cytokine levels measured by flow cytometry in healthy controls at baseline and in RRMS patients between visits during fingolimod treatment
Time frame: Baseline, Month 3, Month 6
Population: Intent to treat. Data analyzed in RRMS patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 % | 76.52 percent of cell count | Standard Error 1.494 |
| Healthy Controls | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 % | 11.57 percent of cell count | Standard Error 0.018 |
| Healthy Controls | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK % | 0.427 percent of cell count | Standard Error 1.328 |
| Healthy Controls | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT % | 5.65 percent of cell count | Standard Error 0.855 |
| Healthy Controls | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 % | 1.05 percent of cell count | Standard Error 0.183 |
| Healthy Controls | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL4+ % (in CD8+) | 5.64 percent of cell count | Standard Error 3.74 |
| FTY720 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL4+ % (in CD8+) | 1.87 percent of cell count | Standard Error 0.538 |
| FTY720 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT % | 5.19 percent of cell count | Standard Error 0.766 |
| FTY720 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 % | 71.92 percent of cell count | Standard Error 1.134 |
| FTY720 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK % | 10.17 percent of cell count | Standard Error 1.169 |
| FTY720 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 % | 13.72 percent of cell count | Standard Error 1.336 |
| FTY720 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 % | 0.93 percent of cell count | Standard Error 0.145 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 % | 6.13 percent of cell count | Standard Error 0.847 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK % | 34.48 percent of cell count | Standard Error 2.758 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT % | 15.55 percent of cell count | Standard Error 1.726 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL4+ % (in CD8+) | 3.13 percent of cell count | Standard Error 0.964 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 % | 5.29 percent of cell count | Standard Error 1.296 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 % | 57.61 percent of cell count | Standard Error 2.401 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 % | 6.20 percent of cell count | Standard Error 1.423 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD8+IL4+ % (in CD8+) | 1.91 percent of cell count | Standard Error 1.225 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 % | 5.14 percent of cell count | Standard Error 0.427 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT % | 17.66 percent of cell count | Standard Error 1.985 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 % | 59.29 percent of cell count | Standard Error 2.318 |
| Visit 3 | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK % | 33.91 percent of cell count | Standard Error 2.238 |
Secondary
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Peripheral blood chemokine cytokine levels measured by flow cytometry during fingolimod treatment in healthy controls at baseline and in RRMS patients between visits
Time frame: Baseline, Month 3, Month 6
Population: Intent to treat. Data analyzed in RRMS patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 abs | 2048.14 pg/ml | Standard Error 263.209 |
| Healthy Controls | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4CD25 (CD3 gate) | 26.08 pg/ml | Standard Error 3.159 |
| Healthy Controls | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 abs | 26.64 pg/ml | Standard Error 4.399 |
| Healthy Controls | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 abs | 311.63 pg/ml | Standard Error 57.592 |
| Healthy Controls | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD4CD25 (CD3 gate) | 2.83 pg/ml | Standard Error 0.383 |
| Healthy Controls | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK abs | 281.33 pg/ml | Standard Error 39.106 |
| Healthy Controls | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT abs | 135.86 pg/ml | Standard Error 16.627 |
| FTY720 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4CD25 (CD3 gate) | 27.03 pg/ml | Standard Error 1.251 |
| FTY720 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT abs | 104.36 pg/ml | Standard Error 15.08 |
| FTY720 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK abs | 623.57 pg/ml | Standard Error 394.837 |
| FTY720 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 abs | 20.44 pg/ml | Standard Error 3.506 |
| FTY720 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD4CD25 (CD3 gate) | 3.33 pg/ml | Standard Error 0.253 |
| FTY720 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 abs | 327.63 pg/ml | Standard Error 44.421 |
| FTY720 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 abs | 1610.94 pg/ml | Standard Error 126.071 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT abs | 88.45 pg/ml | Standard Error 12.725 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 abs | 339.74 pg/ml | Standard Error 43.44 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 abs | 32.9 pg/ml | Standard Error 5.347 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK abs | 203.66 pg/ml | Standard Error 30.487 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 abs | 29.35 pg/ml | Standard Error 8.73 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4CD25 (CD3 gate) | 9.24 pg/ml | Standard Error 1.407 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD4CD25 (CD3 gate) | 2.03 pg/ml | Standard Error 0.302 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NK abs | 181.97 pg/ml | Standard Error 20.715 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD4CD25 (CD3 gate) | 1.77 pg/ml | Standard Error 0.267 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD4CD25 (CD3 gate) | 9.22 pg/ml | Standard Error 1.399 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD19 abs | 26.56 pg/ml | Standard Error 2.879 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | CD3 abs | 314.75 pg/ml | Standard Error 30.15 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | Hi CD16CD56 abs | 30.04 pg/ml | Standard Error 6.59 |
| Visit 3 | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients | NKT abs | 88.98 pg/ml | Standard Error 11.046 |
Secondary
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits
Time frame: Baseline, month 3, month 6
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL17A | 1.06 pg/ml | Standard Error 0.029 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CXCL10=IP-10 (CXCR3 ligand) | 18.18 pg/ml | Standard Error 2.405 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CCL5= RANTES | 404.31 pg/ml | Standard Error 55.189 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL6 | 66.53 pg/ml | Standard Error 65.411 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | VLA4 | 0.58 pg/ml | Standard Error 0.201 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL23 | 3.04 pg/ml | Standard Error 0.924 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | TNF | 1.06 pg/ml | Standard Error 0.1 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CXCL13=BLC | 139.68 pg/ml | Standard Error 46.631 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL4 | 2.36 pg/ml | Standard Error 0.149 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL8 | 3.57 pg/ml | Standard Error 0.553 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL22 | 22.41 pg/ml | Standard Error 0.69 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CCL2=MCP-1 | 62.89 pg/ml | Standard Error 8.42 |
| Healthy Controls | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL13 | 0.3 pg/ml | Standard Error 0.15 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL23 | 2.01 pg/ml | Standard Error 0.629 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | TNF | 1.26 pg/ml | Standard Error 0.196 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CXCL13=BLC | 105.42 pg/ml | Standard Error 20.61 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL6 | 49.98 pg/ml | Standard Error 49.263 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL8 | 3.84 pg/ml | Standard Error 0.482 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL13 | 0.35 pg/ml | Standard Error 0.208 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CCL5= RANTES | 384.12 pg/ml | Standard Error 52.649 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | VLA4 | 0.76 pg/ml | Standard Error 0.356 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CXCL10=IP-10 (CXCR3 ligand) | 18.46 pg/ml | Standard Error 2.356 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CCL2=MCP-1 | 74.38 pg/ml | Standard Error 10.011 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL4 | 1.94 pg/ml | Standard Error 0.099 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL17A | 1.09 pg/ml | Standard Error 0.04 |
| FTY720 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL22 | 22.45 pg/ml | Standard Error 0.843 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CXCL10=IP-10 (CXCR3 ligand) | 20.54 pg/ml | Standard Error 3.008 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL8 | 4.29 pg/ml | Standard Error 0.541 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL17A | 1.04 pg/ml | Standard Error 0.033 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CCL2=MCP-1 | 92.73 pg/ml | Standard Error 13.626 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL6 | 149.62 pg/ml | Standard Error 144.622 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | TNF | 1.12 pg/ml | Standard Error 0.139 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL4 | 2.12 pg/ml | Standard Error 0.145 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL23 | 2.15 pg/ml | Standard Error 0.699 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CCL5= RANTES | 480.34 pg/ml | Standard Error 63.874 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | CXCL13=BLC | 105.86 pg/ml | Standard Error 22.053 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | VLA4 | 0.82 pg/ml | Standard Error 0.36 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL13 | 0.48 pg/ml | Standard Error 0.289 |
| Visit 3 | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | IL22 | 22.99 pg/ml | Standard Error 0.739 |