| . | IT-MSC . | IV-MSC . | Sham treatment . | MSC-IT versus sham, P . | MSC-IV versus sham, P . | MSC-IT versus MSC-IV, P . |
|---|---|---|---|---|---|---|
| Primary end point | ||||||
| Treatment failurea at 6 mob | 6.7% (2/30) | 9.7% (3/31) | 41.9% (13/31) | 0.0003* | 0.0008* | NS |
| Treatment failurec at 6 mob | 31.0% (9/29) | 27.6% (8/29) | 76.7% (23/30) | 0.0004 | 0.0002 | NS |
| Secondary end points | ||||||
| Change in EDSS | ||||||
At 3 mo Median (IQR) | −0.29 ± 0.3 −0.5 (−0.5, 0) | −0.12 ± 0.4 0 (−0.5, 0) | +0.24 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0010 | 0.0624 |
At 6 mo Median (IQR) | −0.20 ± 0.3 0 (−0.5, 0) | −0.13 ± 0.4 0 (−0.5, 0) | +0.30 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0002 | 0.3280 |
| Treatment failurec at 3 mo | 16.1% (5/31) | 24.1% (7/29) | 73.3% (22/30) | <0.0001* | 0.0002* | NS |
| Change in ambulation score | ||||||
At 3 mo Median (IQR) | −0.93 ± 1.1 −1 (−2, 0) | −0.28 ± 1.2 0 (−1, 0) | +1.1 ± 1.2 +1 (0, +2)] | <0.0001 | 0.1938 | 0.0375 |
At 6 mo Median (IQR) | −0.97 ± 1.7 −1 (−1.75, 0) | −0.35 ± 1.1 0 (−1, 0) | +1.3 ± 1.3 +1 (0, +2) | 0.0009 | 0.0938 | 0.1239 |
| Change in sum of functional scores | ||||||
At 3 mo Median (IQR) | −2.81 ± 2.4 −3 (−4, −2) | −1.50 ± 2.1 −1 (−2.25, 0) | +0.48 ± 1.7 +1 (−0.5, +1) | <0.0001 | 0.0009 | 0.0177 |
At 6 mo Median (IQR) | −2.93 ± 2.4 −3 (−4, −2) | −1.29 ± 2.3 −1 (−2, 0) | +0.84 ± 2.1 +1 (−0.5, +2)] | <0.0001 | 0.0006 | 0.0127 |
| Relapses per patient, n, mean ± SD | 0.06 ± 0.25 | 0.28 ± 0.58 | 0.56 ± 0.67 | 0.0005 | 0.052 | 0.074 |
| Proportion/patients relapse-free (n) | 93.8% (30/32) | 78.1% (25/32) | 53.1% (17/32) | 0.001 | 0.1 | |
| T25FW % changes over 6 mo | −5.3 ± 16.3 | −6.4 ± 17.7 | +14.0 ± 25.4 | 0.0017 | 0.0009 | 0.81 |
| 9-HPT % changes over 6 mo | ||||||
| Dominant hand | −3.0 ± 10.1 | −2.1 ± 5.1 | +0.5 ± 8.9 | 0.129 | 0.300 | 0.43 |
| Non-dominant hand | −5.5 ± 7.9 | −1.6 ± 7.5 | +1.3 ± 11.2 | 0.0136 | 0.391 | 0.043 |
| MRI: % monthly changes in FLAIR T2 lesion volume at 6 mo (median) | −0.024 ± 0.053 (−0.004) | −0.016 ± 0.036 (−0.004) | +0.003 ± 0.029 (−0.0) | 0.029 | 0.123 | 0.50 |
| MRI: mean number of Gd-enhancing lesionsb (total lesion number) | 0.17 ± 0.47 (9) | 0.97 ± 1.93 (49) | 0.55 ± 1.03 (30) | 0.0636 | 0.9086 | 0.0776 |
| MRI: % total brain volume change versus baselineb, mean ± SD | ||||||
| At 3 mo | +0.45 ± 1.36 | −0.29 ± 1.16 | −3.58 ± 17.2 | 0.09 | 0.93 | 0.03 |
| At 6 mo | +0.28 ± 1.18 | −0.13 ± 1.48 | +0.29 ± 1.67 | 0.74 | 0.29 | 0.30 |
| PASAT cognitive test % change | ||||||
| At 3 mo | +69.9 ± 204.4 | +37.8 ± 320.0 | −36.1 ± 143.7 | 0.0007 | 0.240 | 0.014 |
| At 6 mo | +11.9 ± 166.2 | +129.5 ± 545.0 | −6.5 ± 203.2 | 0.327 | 0.939 | 0.334 |
| Cognitive test score change at 3 mo (z-scores) | ||||||
| OWAT (KAVE) | +0.474 ± 0.83 | +0.122 ± 0.80 | −0.282 ± 0.60 | 0.013 | 0.12 | |
| SDMT | +0.1 ± 0.7 | −0.3 ± 0.9 | −0.1 ± 0.6 | 0.18 | 0.20 | 0.02 |
| OCT-RNFL (G) % changes over 6 mo (median) | ||||||
| Right eye | −0.2 ± 3.2 (0) | +0.1 ± 2.4 (0) | −0.3 ± 2.7 (−0.4) | 0.844 | 0.429 | 0.57 |
| Left eye | +1.0 ± 2.6 | +0.1 ± 3.2 | −0.7 ± 3.1 | 0.038 | 0.417 | 0.273 |
| % VEP latency changes at 6 mo | ||||||
| Left eye | 0.4 ± 6.6 | 0.7 ± 6.3 | 3.6 ± 15.9 | 0.36 | 0.26 | |
| Right eye | 0.8 ± 5.2 | −1.8 ± 6.9 | 1.8 ± 5.8 | 0.63 | 0.034 | |
| Functional MRI annual changes in motor network, z-scores | ||||||
| Over 3 mo | +0.108 ± 1.06 | +0.036 ± 0.88 | −0.504 ± 1.06 | 0.0675 | 0.0312 | 0.74 |
| Over 6 mo | +0.156 ± 0.684 | −0.06 ± 0.816 | −0.288 ± 0.612 | 0.0425 | 0.0774 | 0.80 |
| Immunology: CD4+/CD25+high T cells % change at 6 mo versus baseline | 307.2 ± 487.5 | 249.5 ± 382.8 | 123.6 ± 281.9 | 0.05 | 0.11 | 0.62 |
| NEDA over 6 mo | 58.6% (17/29) | 40.6% (13/32) | 9.7% (3/31) | <0.0001 | 0.0048 | 0.160 |
| NEDA-4 (including <−0.4% annual change in total brain volume) | 44.8% (13/29) | 28.1% (9/32) | 9.7% (3/31) | 0.005 | 0.12 | 0.17 |
| . | IT-MSC . | IV-MSC . | Sham treatment . | MSC-IT versus sham, P . | MSC-IV versus sham, P . | MSC-IT versus MSC-IV, P . |
|---|---|---|---|---|---|---|
| Primary end point | ||||||
| Treatment failurea at 6 mob | 6.7% (2/30) | 9.7% (3/31) | 41.9% (13/31) | 0.0003* | 0.0008* | NS |
| Treatment failurec at 6 mob | 31.0% (9/29) | 27.6% (8/29) | 76.7% (23/30) | 0.0004 | 0.0002 | NS |
| Secondary end points | ||||||
| Change in EDSS | ||||||
At 3 mo Median (IQR) | −0.29 ± 0.3 −0.5 (−0.5, 0) | −0.12 ± 0.4 0 (−0.5, 0) | +0.24 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0010 | 0.0624 |
At 6 mo Median (IQR) | −0.20 ± 0.3 0 (−0.5, 0) | −0.13 ± 0.4 0 (−0.5, 0) | +0.30 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0002 | 0.3280 |
| Treatment failurec at 3 mo | 16.1% (5/31) | 24.1% (7/29) | 73.3% (22/30) | <0.0001* | 0.0002* | NS |
| Change in ambulation score | ||||||
At 3 mo Median (IQR) | −0.93 ± 1.1 −1 (−2, 0) | −0.28 ± 1.2 0 (−1, 0) | +1.1 ± 1.2 +1 (0, +2)] | <0.0001 | 0.1938 | 0.0375 |
At 6 mo Median (IQR) | −0.97 ± 1.7 −1 (−1.75, 0) | −0.35 ± 1.1 0 (−1, 0) | +1.3 ± 1.3 +1 (0, +2) | 0.0009 | 0.0938 | 0.1239 |
| Change in sum of functional scores | ||||||
At 3 mo Median (IQR) | −2.81 ± 2.4 −3 (−4, −2) | −1.50 ± 2.1 −1 (−2.25, 0) | +0.48 ± 1.7 +1 (−0.5, +1) | <0.0001 | 0.0009 | 0.0177 |
At 6 mo Median (IQR) | −2.93 ± 2.4 −3 (−4, −2) | −1.29 ± 2.3 −1 (−2, 0) | +0.84 ± 2.1 +1 (−0.5, +2)] | <0.0001 | 0.0006 | 0.0127 |
| Relapses per patient, n, mean ± SD | 0.06 ± 0.25 | 0.28 ± 0.58 | 0.56 ± 0.67 | 0.0005 | 0.052 | 0.074 |
| Proportion/patients relapse-free (n) | 93.8% (30/32) | 78.1% (25/32) | 53.1% (17/32) | 0.001 | 0.1 | |
| T25FW % changes over 6 mo | −5.3 ± 16.3 | −6.4 ± 17.7 | +14.0 ± 25.4 | 0.0017 | 0.0009 | 0.81 |
| 9-HPT % changes over 6 mo | ||||||
| Dominant hand | −3.0 ± 10.1 | −2.1 ± 5.1 | +0.5 ± 8.9 | 0.129 | 0.300 | 0.43 |
| Non-dominant hand | −5.5 ± 7.9 | −1.6 ± 7.5 | +1.3 ± 11.2 | 0.0136 | 0.391 | 0.043 |
| MRI: % monthly changes in FLAIR T2 lesion volume at 6 mo (median) | −0.024 ± 0.053 (−0.004) | −0.016 ± 0.036 (−0.004) | +0.003 ± 0.029 (−0.0) | 0.029 | 0.123 | 0.50 |
| MRI: mean number of Gd-enhancing lesionsb (total lesion number) | 0.17 ± 0.47 (9) | 0.97 ± 1.93 (49) | 0.55 ± 1.03 (30) | 0.0636 | 0.9086 | 0.0776 |
| MRI: % total brain volume change versus baselineb, mean ± SD | ||||||
| At 3 mo | +0.45 ± 1.36 | −0.29 ± 1.16 | −3.58 ± 17.2 | 0.09 | 0.93 | 0.03 |
| At 6 mo | +0.28 ± 1.18 | −0.13 ± 1.48 | +0.29 ± 1.67 | 0.74 | 0.29 | 0.30 |
| PASAT cognitive test % change | ||||||
| At 3 mo | +69.9 ± 204.4 | +37.8 ± 320.0 | −36.1 ± 143.7 | 0.0007 | 0.240 | 0.014 |
| At 6 mo | +11.9 ± 166.2 | +129.5 ± 545.0 | −6.5 ± 203.2 | 0.327 | 0.939 | 0.334 |
| Cognitive test score change at 3 mo (z-scores) | ||||||
| OWAT (KAVE) | +0.474 ± 0.83 | +0.122 ± 0.80 | −0.282 ± 0.60 | 0.013 | 0.12 | |
| SDMT | +0.1 ± 0.7 | −0.3 ± 0.9 | −0.1 ± 0.6 | 0.18 | 0.20 | 0.02 |
| OCT-RNFL (G) % changes over 6 mo (median) | ||||||
| Right eye | −0.2 ± 3.2 (0) | +0.1 ± 2.4 (0) | −0.3 ± 2.7 (−0.4) | 0.844 | 0.429 | 0.57 |
| Left eye | +1.0 ± 2.6 | +0.1 ± 3.2 | −0.7 ± 3.1 | 0.038 | 0.417 | 0.273 |
| % VEP latency changes at 6 mo | ||||||
| Left eye | 0.4 ± 6.6 | 0.7 ± 6.3 | 3.6 ± 15.9 | 0.36 | 0.26 | |
| Right eye | 0.8 ± 5.2 | −1.8 ± 6.9 | 1.8 ± 5.8 | 0.63 | 0.034 | |
| Functional MRI annual changes in motor network, z-scores | ||||||
| Over 3 mo | +0.108 ± 1.06 | +0.036 ± 0.88 | −0.504 ± 1.06 | 0.0675 | 0.0312 | 0.74 |
| Over 6 mo | +0.156 ± 0.684 | −0.06 ± 0.816 | −0.288 ± 0.612 | 0.0425 | 0.0774 | 0.80 |
| Immunology: CD4+/CD25+high T cells % change at 6 mo versus baseline | 307.2 ± 487.5 | 249.5 ± 382.8 | 123.6 ± 281.9 | 0.05 | 0.11 | 0.62 |
| NEDA over 6 mo | 58.6% (17/29) | 40.6% (13/32) | 9.7% (3/31) | <0.0001 | 0.0048 | 0.160 |
| NEDA-4 (including <−0.4% annual change in total brain volume) | 44.8% (13/29) | 28.1% (9/32) | 9.7% (3/31) | 0.005 | 0.12 | 0.17 |
Paired t-test, Wilcoxon signed-rank test and Mann-Whitney test, were used as described in the ‘Materials and methods’ section. 9-HPT = 9-hole peg test; mo = months; NEDA = no evidence of disease activity; NS = not significant; OWAT = Owatonna Cognitive Behavioral Test; RNFL = retinal nerve fibre layer; SDMT = Symbol Digit Modalities Test; T25FW - timed 25-foot walking test; VEP = visual evoked potential. *χ2. Values in bold indicate statistically significant difference versus placebo (i.e. P < 0.05).
Confirmed increase in EDSS/1 point in EDSS for patients with baseline scores ≤5.0 and/0.5 degree for baseline EDSS > 5.0.
Pooled analysis/both cycles/treatment.
Increase in at least one Functional System score.
| . | IT-MSC . | IV-MSC . | Sham treatment . | MSC-IT versus sham, P . | MSC-IV versus sham, P . | MSC-IT versus MSC-IV, P . |
|---|---|---|---|---|---|---|
| Primary end point | ||||||
| Treatment failurea at 6 mob | 6.7% (2/30) | 9.7% (3/31) | 41.9% (13/31) | 0.0003* | 0.0008* | NS |
| Treatment failurec at 6 mob | 31.0% (9/29) | 27.6% (8/29) | 76.7% (23/30) | 0.0004 | 0.0002 | NS |
| Secondary end points | ||||||
| Change in EDSS | ||||||
At 3 mo Median (IQR) | −0.29 ± 0.3 −0.5 (−0.5, 0) | −0.12 ± 0.4 0 (−0.5, 0) | +0.24 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0010 | 0.0624 |
At 6 mo Median (IQR) | −0.20 ± 0.3 0 (−0.5, 0) | −0.13 ± 0.4 0 (−0.5, 0) | +0.30 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0002 | 0.3280 |
| Treatment failurec at 3 mo | 16.1% (5/31) | 24.1% (7/29) | 73.3% (22/30) | <0.0001* | 0.0002* | NS |
| Change in ambulation score | ||||||
At 3 mo Median (IQR) | −0.93 ± 1.1 −1 (−2, 0) | −0.28 ± 1.2 0 (−1, 0) | +1.1 ± 1.2 +1 (0, +2)] | <0.0001 | 0.1938 | 0.0375 |
At 6 mo Median (IQR) | −0.97 ± 1.7 −1 (−1.75, 0) | −0.35 ± 1.1 0 (−1, 0) | +1.3 ± 1.3 +1 (0, +2) | 0.0009 | 0.0938 | 0.1239 |
| Change in sum of functional scores | ||||||
At 3 mo Median (IQR) | −2.81 ± 2.4 −3 (−4, −2) | −1.50 ± 2.1 −1 (−2.25, 0) | +0.48 ± 1.7 +1 (−0.5, +1) | <0.0001 | 0.0009 | 0.0177 |
At 6 mo Median (IQR) | −2.93 ± 2.4 −3 (−4, −2) | −1.29 ± 2.3 −1 (−2, 0) | +0.84 ± 2.1 +1 (−0.5, +2)] | <0.0001 | 0.0006 | 0.0127 |
| Relapses per patient, n, mean ± SD | 0.06 ± 0.25 | 0.28 ± 0.58 | 0.56 ± 0.67 | 0.0005 | 0.052 | 0.074 |
| Proportion/patients relapse-free (n) | 93.8% (30/32) | 78.1% (25/32) | 53.1% (17/32) | 0.001 | 0.1 | |
| T25FW % changes over 6 mo | −5.3 ± 16.3 | −6.4 ± 17.7 | +14.0 ± 25.4 | 0.0017 | 0.0009 | 0.81 |
| 9-HPT % changes over 6 mo | ||||||
| Dominant hand | −3.0 ± 10.1 | −2.1 ± 5.1 | +0.5 ± 8.9 | 0.129 | 0.300 | 0.43 |
| Non-dominant hand | −5.5 ± 7.9 | −1.6 ± 7.5 | +1.3 ± 11.2 | 0.0136 | 0.391 | 0.043 |
| MRI: % monthly changes in FLAIR T2 lesion volume at 6 mo (median) | −0.024 ± 0.053 (−0.004) | −0.016 ± 0.036 (−0.004) | +0.003 ± 0.029 (−0.0) | 0.029 | 0.123 | 0.50 |
| MRI: mean number of Gd-enhancing lesionsb (total lesion number) | 0.17 ± 0.47 (9) | 0.97 ± 1.93 (49) | 0.55 ± 1.03 (30) | 0.0636 | 0.9086 | 0.0776 |
| MRI: % total brain volume change versus baselineb, mean ± SD | ||||||
| At 3 mo | +0.45 ± 1.36 | −0.29 ± 1.16 | −3.58 ± 17.2 | 0.09 | 0.93 | 0.03 |
| At 6 mo | +0.28 ± 1.18 | −0.13 ± 1.48 | +0.29 ± 1.67 | 0.74 | 0.29 | 0.30 |
| PASAT cognitive test % change | ||||||
| At 3 mo | +69.9 ± 204.4 | +37.8 ± 320.0 | −36.1 ± 143.7 | 0.0007 | 0.240 | 0.014 |
| At 6 mo | +11.9 ± 166.2 | +129.5 ± 545.0 | −6.5 ± 203.2 | 0.327 | 0.939 | 0.334 |
| Cognitive test score change at 3 mo (z-scores) | ||||||
| OWAT (KAVE) | +0.474 ± 0.83 | +0.122 ± 0.80 | −0.282 ± 0.60 | 0.013 | 0.12 | |
| SDMT | +0.1 ± 0.7 | −0.3 ± 0.9 | −0.1 ± 0.6 | 0.18 | 0.20 | 0.02 |
| OCT-RNFL (G) % changes over 6 mo (median) | ||||||
| Right eye | −0.2 ± 3.2 (0) | +0.1 ± 2.4 (0) | −0.3 ± 2.7 (−0.4) | 0.844 | 0.429 | 0.57 |
| Left eye | +1.0 ± 2.6 | +0.1 ± 3.2 | −0.7 ± 3.1 | 0.038 | 0.417 | 0.273 |
| % VEP latency changes at 6 mo | ||||||
| Left eye | 0.4 ± 6.6 | 0.7 ± 6.3 | 3.6 ± 15.9 | 0.36 | 0.26 | |
| Right eye | 0.8 ± 5.2 | −1.8 ± 6.9 | 1.8 ± 5.8 | 0.63 | 0.034 | |
| Functional MRI annual changes in motor network, z-scores | ||||||
| Over 3 mo | +0.108 ± 1.06 | +0.036 ± 0.88 | −0.504 ± 1.06 | 0.0675 | 0.0312 | 0.74 |
| Over 6 mo | +0.156 ± 0.684 | −0.06 ± 0.816 | −0.288 ± 0.612 | 0.0425 | 0.0774 | 0.80 |
| Immunology: CD4+/CD25+high T cells % change at 6 mo versus baseline | 307.2 ± 487.5 | 249.5 ± 382.8 | 123.6 ± 281.9 | 0.05 | 0.11 | 0.62 |
| NEDA over 6 mo | 58.6% (17/29) | 40.6% (13/32) | 9.7% (3/31) | <0.0001 | 0.0048 | 0.160 |
| NEDA-4 (including <−0.4% annual change in total brain volume) | 44.8% (13/29) | 28.1% (9/32) | 9.7% (3/31) | 0.005 | 0.12 | 0.17 |
| . | IT-MSC . | IV-MSC . | Sham treatment . | MSC-IT versus sham, P . | MSC-IV versus sham, P . | MSC-IT versus MSC-IV, P . |
|---|---|---|---|---|---|---|
| Primary end point | ||||||
| Treatment failurea at 6 mob | 6.7% (2/30) | 9.7% (3/31) | 41.9% (13/31) | 0.0003* | 0.0008* | NS |
| Treatment failurec at 6 mob | 31.0% (9/29) | 27.6% (8/29) | 76.7% (23/30) | 0.0004 | 0.0002 | NS |
| Secondary end points | ||||||
| Change in EDSS | ||||||
At 3 mo Median (IQR) | −0.29 ± 0.3 −0.5 (−0.5, 0) | −0.12 ± 0.4 0 (−0.5, 0) | +0.24 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0010 | 0.0624 |
At 6 mo Median (IQR) | −0.20 ± 0.3 0 (−0.5, 0) | −0.13 ± 0.4 0 (−0.5, 0) | +0.30 ± 0.4 0 (0, +0.5) | <0.0001 | 0.0002 | 0.3280 |
| Treatment failurec at 3 mo | 16.1% (5/31) | 24.1% (7/29) | 73.3% (22/30) | <0.0001* | 0.0002* | NS |
| Change in ambulation score | ||||||
At 3 mo Median (IQR) | −0.93 ± 1.1 −1 (−2, 0) | −0.28 ± 1.2 0 (−1, 0) | +1.1 ± 1.2 +1 (0, +2)] | <0.0001 | 0.1938 | 0.0375 |
At 6 mo Median (IQR) | −0.97 ± 1.7 −1 (−1.75, 0) | −0.35 ± 1.1 0 (−1, 0) | +1.3 ± 1.3 +1 (0, +2) | 0.0009 | 0.0938 | 0.1239 |
| Change in sum of functional scores | ||||||
At 3 mo Median (IQR) | −2.81 ± 2.4 −3 (−4, −2) | −1.50 ± 2.1 −1 (−2.25, 0) | +0.48 ± 1.7 +1 (−0.5, +1) | <0.0001 | 0.0009 | 0.0177 |
At 6 mo Median (IQR) | −2.93 ± 2.4 −3 (−4, −2) | −1.29 ± 2.3 −1 (−2, 0) | +0.84 ± 2.1 +1 (−0.5, +2)] | <0.0001 | 0.0006 | 0.0127 |
| Relapses per patient, n, mean ± SD | 0.06 ± 0.25 | 0.28 ± 0.58 | 0.56 ± 0.67 | 0.0005 | 0.052 | 0.074 |
| Proportion/patients relapse-free (n) | 93.8% (30/32) | 78.1% (25/32) | 53.1% (17/32) | 0.001 | 0.1 | |
| T25FW % changes over 6 mo | −5.3 ± 16.3 | −6.4 ± 17.7 | +14.0 ± 25.4 | 0.0017 | 0.0009 | 0.81 |
| 9-HPT % changes over 6 mo | ||||||
| Dominant hand | −3.0 ± 10.1 | −2.1 ± 5.1 | +0.5 ± 8.9 | 0.129 | 0.300 | 0.43 |
| Non-dominant hand | −5.5 ± 7.9 | −1.6 ± 7.5 | +1.3 ± 11.2 | 0.0136 | 0.391 | 0.043 |
| MRI: % monthly changes in FLAIR T2 lesion volume at 6 mo (median) | −0.024 ± 0.053 (−0.004) | −0.016 ± 0.036 (−0.004) | +0.003 ± 0.029 (−0.0) | 0.029 | 0.123 | 0.50 |
| MRI: mean number of Gd-enhancing lesionsb (total lesion number) | 0.17 ± 0.47 (9) | 0.97 ± 1.93 (49) | 0.55 ± 1.03 (30) | 0.0636 | 0.9086 | 0.0776 |
| MRI: % total brain volume change versus baselineb, mean ± SD | ||||||
| At 3 mo | +0.45 ± 1.36 | −0.29 ± 1.16 | −3.58 ± 17.2 | 0.09 | 0.93 | 0.03 |
| At 6 mo | +0.28 ± 1.18 | −0.13 ± 1.48 | +0.29 ± 1.67 | 0.74 | 0.29 | 0.30 |
| PASAT cognitive test % change | ||||||
| At 3 mo | +69.9 ± 204.4 | +37.8 ± 320.0 | −36.1 ± 143.7 | 0.0007 | 0.240 | 0.014 |
| At 6 mo | +11.9 ± 166.2 | +129.5 ± 545.0 | −6.5 ± 203.2 | 0.327 | 0.939 | 0.334 |
| Cognitive test score change at 3 mo (z-scores) | ||||||
| OWAT (KAVE) | +0.474 ± 0.83 | +0.122 ± 0.80 | −0.282 ± 0.60 | 0.013 | 0.12 | |
| SDMT | +0.1 ± 0.7 | −0.3 ± 0.9 | −0.1 ± 0.6 | 0.18 | 0.20 | 0.02 |
| OCT-RNFL (G) % changes over 6 mo (median) | ||||||
| Right eye | −0.2 ± 3.2 (0) | +0.1 ± 2.4 (0) | −0.3 ± 2.7 (−0.4) | 0.844 | 0.429 | 0.57 |
| Left eye | +1.0 ± 2.6 | +0.1 ± 3.2 | −0.7 ± 3.1 | 0.038 | 0.417 | 0.273 |
| % VEP latency changes at 6 mo | ||||||
| Left eye | 0.4 ± 6.6 | 0.7 ± 6.3 | 3.6 ± 15.9 | 0.36 | 0.26 | |
| Right eye | 0.8 ± 5.2 | −1.8 ± 6.9 | 1.8 ± 5.8 | 0.63 | 0.034 | |
| Functional MRI annual changes in motor network, z-scores | ||||||
| Over 3 mo | +0.108 ± 1.06 | +0.036 ± 0.88 | −0.504 ± 1.06 | 0.0675 | 0.0312 | 0.74 |
| Over 6 mo | +0.156 ± 0.684 | −0.06 ± 0.816 | −0.288 ± 0.612 | 0.0425 | 0.0774 | 0.80 |
| Immunology: CD4+/CD25+high T cells % change at 6 mo versus baseline | 307.2 ± 487.5 | 249.5 ± 382.8 | 123.6 ± 281.9 | 0.05 | 0.11 | 0.62 |
| NEDA over 6 mo | 58.6% (17/29) | 40.6% (13/32) | 9.7% (3/31) | <0.0001 | 0.0048 | 0.160 |
| NEDA-4 (including <−0.4% annual change in total brain volume) | 44.8% (13/29) | 28.1% (9/32) | 9.7% (3/31) | 0.005 | 0.12 | 0.17 |
Paired t-test, Wilcoxon signed-rank test and Mann-Whitney test, were used as described in the ‘Materials and methods’ section. 9-HPT = 9-hole peg test; mo = months; NEDA = no evidence of disease activity; NS = not significant; OWAT = Owatonna Cognitive Behavioral Test; RNFL = retinal nerve fibre layer; SDMT = Symbol Digit Modalities Test; T25FW - timed 25-foot walking test; VEP = visual evoked potential. *χ2. Values in bold indicate statistically significant difference versus placebo (i.e. P < 0.05).
Confirmed increase in EDSS/1 point in EDSS for patients with baseline scores ≤5.0 and/0.5 degree for baseline EDSS > 5.0.
Pooled analysis/both cycles/treatment.
Increase in at least one Functional System score.
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