Table 1. Description of All Study Patients With a First Demyelinating Event (N = 1128).
| Characteristic | All included patients (N = 1128) | PIRA (n = 277) | No PIRA (n = 851) | P value, PIRA vs no PIRA | Early PIRA (n = 86) | Late PIRA (n = 191) | P value, early PIRA vs late PIRA | Active PIRA (n = 73) | Nonactive PIRA (n = 71) | P value, active vs nonactive PIRA |
|---|---|---|---|---|---|---|---|---|---|---|
| Age at first attack, mean (SD), y | 32.1 (8.3) | 33.0 (8.2) | 31.8 (8.3) | .05a | 34.8 (7.9) | 32.1 (8.3) | .01a | 31.1 (8.3) | 35.2 (8.3) | .004a |
| Sex, No. (%) | ||||||||||
| Male | 347 (30.8) | 87 (31.4) | 260 (30.6) | .85b | 33 (38.4) | 54 (28.3) | .12b | 29 (39.7) | 17 (23.9) | .06b |
| Female | 781 (69.2) | 190 (68.6) | 591 (69.4) | 53 (61.6) | 137 (71.7) | 44 (60.3) | 54 (76.1) | |||
| Topography of first attack, patient No. (%) | ||||||||||
| Optic nerve | 385 (34.1) | 91 (32.9) | 294 (34.5) | .69b | 20 (23.3) | 71 (37.2) | .14b | 17/73 (23.3) | 29/71 (40.8) | .14b |
| Brainstem | 283 (25.1) | 74 (26.7) | 209 (24.6) | 27 (31.4) | 47 (24.6) | 23/73 (31.5) | 15/71 (21.1) | |||
| Spinal cord | 333 (29.5) | 86 (31.1) | 247 (29.0) | 29 (33.7) | 57 (29.8) | 26/73 (35.6) | 21/71 (29.6) | |||
| Other | 121 (10.7) | 26 (9.4) | 95 (11.2) | 10 (11.6) | 16 (8.4) | 7/73 (9.6) | 6/71 (8.5) | |||
| T2 lesion No. category at first attack, patient No. (%) | ||||||||||
| 0 Lesions | 280/1077 (26.0) | 54/268 (20.2) | 226/809 (27.9) | .03b | 15/83 (18.1) | 39/185 (21.1) | 36b | 3/72 (4.2) | 21/69 (30.4) | <.001b |
| 1-3 Lesions | 154/1077 (14.3) | 34/268 (12.7) | 120/809 (14.8) | 7 /83 (8.4) | 27/185 (14.6) | 10/72 (13.9) | 10/69 (14.5) | |||
| 4-8 Lesions | 137/1077 (12.7) | 38/268 (14.2) | 99/809 (12.2) | 11 /83 (13.3) | 27/185 (14.6) | 10/72 (13.9) | 12/69 (17.4) | |||
| ≥9 Lesions | 506/1077 (47.0) | 142/268 (53.0) | 364/809 (45.0) | 50/83 (60.2) | 92/185 (49.7) | 49/72 (68.1) | 26/69 (37.7) | |||
| ≥1 lnfratentorial lesion category at first attack, patient No. (%) | 436/836 (52.2) | 83/188 (44.2) | 353/648 (54.5) | .02b | 41/70 (58.6) | 64/118 (54.2) | .67b | 39/54 (72.2) | 15/49 (30.6) | <.001b |
| Spinal cord lesion category at first attack, patient No. (%) | ||||||||||
| 0 Lesions | 423/661 (64.0) | 111/154 (72.1) | 312/507 (61.5) | .11b | 34/57 (59.6) | 77/97 (79.4) | .05b | 20/33 (61.1) | 35/47 (74.5) | .10b |
| 1 Lesion | 120 /661 (18.2) | 20/154 (13.0) | 100/507 (19.7) | 12/57 (21.1) | 8/97 (8.2) | 4/33 (12.1) | 7/47 (14.9) | |||
| 2-3 Lesions | 55/661 (8.3) | 11/154 (7.1) | 44/507 (8.7) | 6/57 (10.5) | 5/97 (5.2) | 6/33 (18.2) | 1/47 (2.1) | |||
| ≥4 Lesions | 63/661 (9.5) | 12/154 (7.8) | 51/507 (10.1) | 5/57 (8.8) | 7/97 (7.2) | 3/33 (9.1) | 4/47 (8.5) | |||
| No. of CEL category at first attack, patient No. (%) | ||||||||||
| 0 Lesions | 523/804 (65.1) | 124/190 (65.3) | 399/614 (65.0) | .99b | 39/66 (59.1) | 85/124 (68.5) | .18b | 36/59 (61.0) | 39/47 (83.0) | .03b |
| 1 Lesion | 117/804 (14.6) | 28/190 (14.7) | 89 /614 (14.5) | 14/66 (21.2) | 14/124 (11.3) | 10/59 (16.9) | 2/47 (4.3) | |||
| >1 Lesions | 164/804 (20.4) | 38/190 (20.0) | 126/614 (20.5) | 13/66 (19.7) | 25/124 (20.2) | 13/59 (22.0) | 6/47 (12.8) | |||
| Presence of OBs at first attack, No. (%) | 577/956 (60.4) | 158/234 (67.5) | 419/722 (58.0) | .01b | 50/73 (68.5) | 108/161 (67.1) | .95b | 51/63 (81.0) | 35/60 (58.3) | .01b |
| Follow-up characteristics | ||||||||||
| Follow-up time, median (IQR), y | 10.46 (5.2-17.1) | 16.95 (11.5-20.9) | 8.65 (4.4-14.1) | <.001c | 13.0 (6.8-18.7) | 17.9 (13.2-21.4) | <.001c | 17.1 (11.8-21.2) | 14.1 (8.3-19.7) | .06c |
| Time to first PIRA, median (IQR), y | 7.22 (4.6-12.4) | 7.22 (4.6-12.4) | NA | NA | 3.8 (3.0-4.4) | 10.1 (7.0-14.7) | <.001c | 6.6 (4.4-10.8) | 6.9 (3.4-11.9) | .56c |
| ARR considering the whole follow-up, median (IQR) | 0.21 (0.1-0.4) | 0.17 (0.1-0.3) | 0.2 (0.1-0.4) | <.001c | 0.2 (0.1-0.3) | 0.2 (0.1-0.3) | .10c | 0.2 (0.2-0.4) | 0.1 (0.1-0.3) | <.001c |
| No. of patients treated with DMTs at any time during follow-up (%)d | 580/1109 (52.3)d | 166/274 (60.6)d | 414/835 (49.6)d | .002b | 57/84 (67.9) | 109/190 (57.4) | .13b | 64/72 (88.9) | 30/71 (42.3) | <.001b |
| Proportion of time receiving DMT during whole follow-upe | ||||||||||
| Median (IQR) | 0.1 (0-0.8) | 0.4 (0-0.9) | 0 (0-0.8) | .006c | 0.6 (0-0.9) | 0.33 (0-0.8) | .05c | 0.7 (0.5-0.9) | 0 (0-0.7) | <.001c |
| Mean (SD) | 0.4 (0.4) | 0.4 (0.4) | 0.4 (0.4) | 0.5 (0.4) | 0.4 (0.4) | 0.6 (0.3) | 0.3 (0.4) |
Abbreviations: ARR, annualized relapse rate; CEL, contrast-enhancing lesion; DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; HR, hazard ratio; IT, interaction term; NA, not applicable; OB, oligoclonal band; PIRA, progression independent of relapse activity.
a
t Test.
b
χ2 Test.
c
Mann-Whitney U test (comparison of medians).
d
We have excluded those patients who were part of a randomized clinical trial (n = 19) because they could have received placebo (we do not have information on treatment allocation).
e
In the numerator, we have only considered those periods of time outside clinical trials, since we are still blinded to treatment allocation in some (n = 51) of those patients who have participated in clinical trials (n = 71), ie, those periods of time within a clinical trial have been considered as if the patient was not treated.