1
Online-only Supplement
eFigure 1. Kaplan-Meier plot of time to 3-month confirmed disability progression by baseline pNfL stratified for superimposed relapse status prior to study
(EXPAND)
≥30
<30
393 395
307 325
168 215
85 95
29 30
0 6 12 18 24 30
Time (months)
Proportion of patients with 3mCDP
pNfL at baseline (pg/mL)
≥30
<30
HR (95% CI): 1.26 (0.98; 1.62), p=0.0723
Without relapses With relapses
80 70 60 50 40 30 20 10 0
≥30
<30
224 211
185 176
117 123
64 76
14 19
0 6 12 18
Time (months)
24 30
Proportion of patients with 3mCDP
pNfL at baseline (pg/mL)
≥30
<30
HR (95% CI): 1.45 (1.05; 2.01), p=0.0239
3mCDP, 3 month confirmed disability progression; CI, confidence interval; HR, hazard ratio; pNfL, plasma neurofilament light; SPMS, secondary progressive multiple sclerosis
80 70 60 50 40 30 20 10 0 270
240 460
437
1 eFigure 2. Kaplan-Meier plot of time to 6-month confirmed disability progression by baseline pNfL in (A) EXPAND (SPMS), (B) INFORMS (PPMS)
(A)
(B)
6mCDP, 6 month confirmed disability progression; CI, confidence interval; HR, hazard ratio; pNfL, plasma neurofilament light; SPMS, secondary progressive multiple sclerosis
Online-only Supplement
eFigure 3. Kaplan Meier plot of time to 6mCDP
SDMTby baseline pNfL in (A) overall EXPAND study; (B) by baseline Gd
+status; (C) by baseline relapse status in EXPAND
(A)
20
15
10
0
≥30
<30
30
732678
633 617
Numbers at risk
467 495
266 322
128 165
31 47
pNfL at baseline (pg/mL)
≥30 (High)
<30 (Low)
25
Proportion of patients with 6mCDP SDMT
HR (95% CI): 1.41 (1.09; 1.84), p=0.0103
0 6 12 18 24
Time (months)
6mCDPSDMT, time to 6 month confirmed 4-point SDMT progression; CI, confidence interval; HR, hazard ratio; pNfL, plasma neurofilament light; SDMT, Symbol Digit Modalities Test
5
Proportion of patients with 6mCDPSDMTProportion of patients with 6mCDPSDMT Proportion of patients with 6mCDPSDMTProportion of patients with 6mCDPSDMT
(C) Without relapses
HR (95% CI): 2.35 (1.09; 5.06), p=0.0289
HR (95% CI): 1.34 (0.99; 1.83), p=0.0613
25 20 15 10 5
0 6 24 30
Numbers at risk
≥30 4920
<30 576
426 524
310 419
182 269
83 139
21 35 pNfL at baseline (pg/mL)
≥30
<30 25
20 15 10 5
0 6 12 18 24 30
Time (months) Numbers at risk
≥30 221 0
<30 78
192 72
146 59
80 44
44 22
9 10 pNfL at baseline (pg/mL)
≥30
<30
25 20 15 10 5
24 30
12 18
Time (months)
≥30 4600
<30 437
398 400
286 325
154 208
68 100
20 29 p=0.0755
pNfL at baseline (pg/mL)
≥30
<30
HR (95% CI): 1.39 (0.99; 1.93), p=0.0556
25 20 15 10 5
0 6 12 18 24 30 0 6
Time (months) Numbers at risk
≥30 0 270 233
<30 240 216
179 169
112 113
60 65
11 18
With relapses
pNfL at baseline (pg/mL) ≥30
<30
HR (95% CI): 1.49 (0.96; 2.31),
Numbers at risk
12 18
Time (months)
6mCDPSDMT, time to 6 months confirmed 4-point SDMT progression; CI, confidence interval; Gd+, gadolinium-enhancing; HR, hazard ratio; pNfL, plasma neurofilament light; SDMT, Symbol Digit Modalities Test
1
Online-only Supplement
eFigure 4. Kaplan Meier plot of time to 6mCDP
PASATby baseline pNfL in EXPAND
Proportion of patients with 6mCDPPASAAT
6mCDPPASAT, time to 6 months confirmed 20% PASAT progression; CI, confidence interval; Gd+, gadolinium-enhancing; HR, hazard ratio;
PASAT, Paced Auditory Serial Addition test; pNfL, plasma neurofilament light
1 eTable 1. Visit windows for pNfL assessments in the EXPAND study
Visit Start Day Target Day End day
Month 3 2 90 179
Month 12 180 360 540
Month 24 541 720 900
Month 36 901 1080 1260
pNfL, plasma neurofilament light chain
1
Online-only Supplement
eTable 2: Cox regression of time to 3-months confirmed CDP on pNfL at baseline by treatment groups using variable cutoffs for pNfL
pNfL at BL n/N Month 30 KM estimate (%)
HR (95% CI) HR as risk difference
(%)
p-value
EXPAND siponimod arm
≥28 pg/mL 155/548 36.0
1.20 (0.93; 1.55) 20.1% 0.1551
<28 pg/mL 103/396 31.0
≥30 pg/mL 144/495 37.3
1.32 (1.03; 1.69) 31.7% 0.0312
<30 pg/mL 114/449 30.3
≥32 pg/mL 129/438 37.8
1.31 (1.03; 1.69) 31.5% 0.0312
<32 pg/mL 129/506 30.6 EXPAND placebo arm
≥28 pg/mL 95/259 51.8
1.55 (1.11; 2.16) 55.3% 0.0094
<28 pg/mL 58/204 31.9
≥30 pg/mL 83/235 49.1
1.34 (0.97, 1.86) 34.3% 0.0737
<30 pg/mL 70/228 36.0
≥32 pg/mL 76/213 49.7
1.35 (0.98, 1.85) 34.5% 0.0703
<32 pg/mL 77/250 36.3 INFORMS fingolimod arm
≥28 pg/mL 21/44 47.7
1.16 (0.68, 1.97) 16.0% 0.5809
<28 pg/mL 48/106 44.6
≥30 pg/mL 18/35 52.2
1.26 (0.73, 2.16) 25.7% 0.4087
<30 pg/mL 51/115 43.4
≥32 pg/mL 17/31 56.4
1.42 (0.82, 2.47) 42.4% 0.2080
<32 pg/mL 52/119 42.6
INFORMS placebo arm
2 1.56 (1.02, 2.39) 56.1% 0.0410
<28 pg/mL 63/143 43.2
≥30 pg/mL 25/41 55.4
1.66 (1.04, 2.63) 65.5% 0.0326
<30 pg/mL 70/156 43.8
≥32 pg/mL 22/33 59.4
1.91 (1.18, 3.10) 91.2% 0.0084
<32 pg/mL 73/164 43.7
BL, baseline; CDP, confirmed disability progression; CI, confidence interval; HR, hazard ratio; KM, Kaplan Meier
The Cox regression model included the explanatory variables study, NfL category, age, baseline EDSS and superimposed relapses in 2 years prior to study (only in EXPAND).
