Table 1.
Clinical and demographical characteristics of CIS/RRMS patients included in the study and dichotomized by EDA/NEDA and non-PIRA/PIRA status at follow-up
| Variable | Total CIS/RRMS patients (n = 131) | NEDA (n = 70) | EDA (n = 61) | p-value | Non-PIRA (n = 113) | PIRA (n = 18) | p-value |
|---|---|---|---|---|---|---|---|
| Age, median (IQR) | 34 (28–42) | 35.5 (27.7–44) | 32 (28–41) | 0.56a | 34 (28–41) | 34 (28–44.5) | 0.7a |
| Sex (Female), n (%) | 91 (69.5) | 51 (72.9) | 40 (65.6) | 0.45b | 80 (70.8) | 11 (61.1) | 0.42b |
| Disease duration from symptom onset to sampling, m, mean ± SD | 25.8 ± 51.1 | 32.5 ± 65 | 18.1 ± 37.1 | 0.13c | 25.1 ± 53.5 | 30.4 ± 59.6 | 0.7c |
| Total follow-up time from first to last visit, m, median (IQR) | 41 (33–72) | 40 (32.5–48) | 47 (33–84) | 0.022a | 41 (31 -72) | 48.5 (37.5–100.5) | 0.0504a |
| Onset EDSS, median (IQR) | 2 (1–3) | 2 (1–3) | 2 (1–2.75) | 0.72a | 2 (1–2.75) | 2 (1–3) | 0.64a |
| BL/RBL EDSS, median (IQR) | 2 (1–3) | 2 (1.4–3) | 1.5 (1–2.5) | 0.1a | 2 (1.3–3) | 1 (1–1.5) | 0.004a |
| Disease course at sampling, n (%) | |||||||
| CIS | 17 (13) | 2 (2.9) | 15 (24.6) | < 0.001b | 16 (14.2) | 1 (5.6) | 0.46b |
| RRMS | 114 (87) | 68 (97.1) | 46 (75.4) | 97 (85.8) | 17 (94.4) | ||
| BL T2W lesions, n (%) | 0.86b | 0.13b | |||||
| < 10 | 61 (46.6) | 32 (45.7) | 29 (47.5) | 56 (49.6) | 5 (27.8) | ||
| ≥ 10 | 70 (53.4) | 38 (54.3) | 32 (52.5) | 57 (50.4) | 13 (72.2) | ||
| CEL, n (%) | 70 (53.4) | 36 (51.4) | 34 (55.7) | 0.73b | 62 (54.9) | 8 (44.4) | 0.45b |
| IgG OCBs ≥ 2, n (%) | 128 (97.7) | 68 (97.1) | 60 (98.4) | 1.0b | 110 (97.3) | 18 (100) | 1.0b |
| Qalb (× 103), median (IQR) | 3.9 (3.1–5.5) | 3.9 (2.9–5.2) | 3.9 (3.2–5.9) | 0.76a | 3.9 (3.2–5.5) | 4.15 (2.6–5.9) | 0.91a |
| CSF KFLC mg/L, median (IQR) | 4.8 (2.1–9.9) | 3.7 (1.6–8.5) | 6.17 (3.5–13) | 0.003a | 4.1 (1.8–9.9) | 8.8 (4.6–19.3) | 0.008a |
| Serum KFLC mg/L, median (IQR) | 13 (10.4–16.2) | 13.5 (10.6–17.1) | 12.9 (10.3–14.8) | 0.31a | 13 (10.4–16.1) | 12.7 (10.4–16.3) | 0.88a |
| KFLC index, median (IQR) | 96.1 (30.1–187) | 66.3 (25.3–177.2) | 121.4 (56.7–191.4) | 0.015a | 78.3 (28.9–186.5) | 148.5 (106.9–253.5) | 0.009a |
| IgG index, median (IQR) | 0.89 (0.68–1.34) | 0.81 (0.64–1.3) | 0.93 (0.75–1.42) | 0.083a | 0.86 (0.65–1.31) | 1.12 (0.91–1.81) | 0.016a |
| CSF NfL ng/L, median (IQR) | 970 (530–2160) | 975 (575–2163) | 930 (505–2185) | 0.92a | 970 (550–2040) | 980 (330–2498) | 0.99a |
| Tau ng/L, median (IQR) | 198 (163.5–268) | 194 (158–232) | 224.5 (172.8–299) | 0.048a | 198 (163–267) | 215 (163–324.5) | 0.58a |
| CSF GFAP ng/L, median (IQR) | 330 (230–440) | 320 (227.5–442.5) | 350 (245–440) | 0.42a | 330 (230–420) | 370 (257.5–465) | 0.39a |
| Time from sampling to DMT start, d, median (IQR) | 34 (19–100) | 31 (19–49) | 55 (19–196.5) | 0.018a | 35 (20–105.3) | 27 (0–59) | 0.03a |
| Treatment strategy, n (%) | < 0.001b | 0.3b | |||||
| First-line | 41 (31.3) | 23 (32.9) | 18 (29.5) | 36 (31.9) | 5 (27.8) | ||
| Escalation | 15 (11.5) | 1 (1.4) | 14 (23) | 11 (9.7) | 4 (22.2) | ||
| he-DMT | 75 (57.3) | 46 (65.7) | 29 (47.5) | 66 (58.4) | 9 (50) | ||
| Dominant DMT during the whole follow-up, n (%): | 0.08b | 0.13b | |||||
| No DMT | 3 (2.3) | 3 (4.3) | 0 (0) | 3 (2.7) | 0 (0) | ||
| Dimethyl fumarate | 27 (20.6) | 9 (12.9) | 18 (29.5) | 24 (21.2) | 3 (16.7) | ||
| Teriflunomide | 3 (2.3) | 2 (2.9) | 1 (1.6) | 2 (1.8) | 1 (5.6) | ||
| Fingolimod | 6 (4.6) | 1 (1.4) | 5 (8.2) | 3 (2.7) | 3 (16.7) | ||
| Natalizumab | 32 (24.4) | 20 (28.6) | 12 (19.7) | 31 (27.4) | 1 (5.6) | ||
| Rituximab | 41 (31.3) | 25 (35.7) | 16 (26.2) | 34 (30.1) | 7 (38.9) | ||
| Cladribine | 13 (9.9) | 8 (11.4) | 5 (8.2) | 11 (9.7) | 2 (11.1) | ||
| Alemtuzumab | 4 (3.1) | 1 (1.4) | 3 (4.9) | 3 (2.7) | 1 (5.6) | ||
| AHSCT | 2 (1.5) | 1 (1.4) | 1 (1.6) | 2 (1.8) | 0 (0) |
Bold text indicates p values < 0.05
CIS clinically isolated syndrome, RRMS relapsing–remitting multiple sclerosis, NEDA no evidence of disease activity, EDA evidence of disease activity, PIRA progression independent of relapse activity, SD standard deviation, BL baseline, RBL re-baseline, EDSS expanded disability status scale, IQR interquartile range, MRI magnetic resonance imaging, IgG immunoglobulin G, OCB oligoclonal bands, KFLC kappa free light chain, Qalb albumin quotient, CSF cerebrospinal fluid, NfL neurofilament light, GFAP glial fibrillary acidic protein, CEL contrast-enhancing lesion, he high-efficacy, DMT disease modifying therapy, AHSCT autologous hematopoietic stem cell transplantation
Data are shown as median and interquartile range unless otherwise specified
aMann–Whitney U test
bFisher’s exact test or Pearson chi-square test
cUnpaired T-test