Introduction
Methods
Study design and setting
Standard protocol approvals, registrations, and patient consent
Patients
Assessments and data collection
Demographic and clinical data
Quality of life
Worsened and non-worsened patients
Study outcomes
Statistical analysis
Results
Patient characteristics
Total sample° | Worsened patients* | Non-worsened patients* | |||
---|---|---|---|---|---|
N = 580 | N = 107 | N = 417 | p | ||
Female, n (%) | 419 (72.2) | 75 (70.1) | 300 (71.9) | 0.71 | |
Age (years) | M (SD) | 41.3 (10.2) | 43.2 (10.2) | 40.9 (10.1) |
0.02
|
Min, max | 18, 71 | 19, 64 | 18, 69 | ||
Marital status, n (%) | Cohabiting/married Divorced/separated/single/widowed | 393 (67.8) | 73 (68.2) | 282 (67.6) | 0.91 |
187 (32.2) | 34 (31.8) | 73 (68.2) | |||
Employment status, n (%) | Employed | 335 (57.8) | 59 (55.1) | 241 (57.8) | 0.62 |
Unemployed/homemaker/retired/student | 245 (42.2) | 48 (44.9) | 176 (42.2) | ||
Educational level, n (%) | Elementary school | 113 (19.5) | 31 (28.4) | 76 (18.2) |
0.03
|
College | 81 (14.0) | 9 (8.3) | 61 (14.6) | ||
High school/university | 386 (66.6) | 67 (63.3) | 280 (67.1) | ||
EDSS score | M (SD) | 2.9 (1.9) | 3.5 (2.2) | 2.8 (1.8) |
<10
-3
|
Median | 2.5 | 4.0 | 2.0 | ||
Min, max | 0.0, 7.5 | 0.0, 7.0 | 0.0, 7.0 | ||
MS course, n (%) | Relapsing-remitting | 510 (87.9) | 79 (73.8) | 381 (91.4) |
<10
-3
|
Secondary progressive | 53 (9.1) | 18 (16.8) | 30 (7.2) | ||
Primary progressive | 12 (2.1) | 8 (7.5) | 2 (0.5) | ||
Primary relapsing | 5 (0.9) | 2 (1.9) | 4 (1.0) | ||
Time since first MS symptom (years) | M (SD) | 10.0 (7.5) | 10.2 (8.1) | 9.9 (7.2) | 0.98 |
Min, max | 0, 45 | 0, 45 | 0.0, 40 | ||
Number of relapses in previous 2 years | M (SD) | 1.3 (1.4) | 1.4 (1.6) | 1.3 (1.3) | 0.33 |
0 | 187 (32.2) | 37 (34.6) | 135 (32.4) | ||
1 | 185 (31.9) | 27 (25.2) | 137 (32.9) | ||
2 | 123 (21.2) | 23 (21.5) | 87 (20.9) | ||
> = 3 | 85 (14.7) | 20 (18.7) | 58 (13.9) |
Responsiveness of MusiQoL and SF-36 at month 24 in worsened patients
Baseline | Month 6 | Month 12 | Month 18 | Month 24 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MusiQoL | M (SD) | M (SD) | D
M6-BL
| ES | M (SD) | D
M12-BL
| ES | M (SD) | D
M18-BL
| ES | M (SD) | D
M24-BL
| ES |
ADL | 50.0 (24.4) | 46.9 (25.2) | −3.33 | −0.14 | 49.4 (26.1) | −1.04 | −0.04 | 47.1 (26.9) | −3.04 | −0.12 | 46.8 (28.2) | −3.53 | −0.14 |
PWB | 62.6 (22.1) | 62.5 (23.0) | −0.56 | −0.02 | 64.8 (22.5) | 2.04 | 0.09 | 61.7 (23.2) | −1.33 | −0.06 | 64.3 (23.9) | 1.67 | 0.08 |
SPT | 64.7 (21.3) | 68.1 (21.6) | 3.54*
| 0.16 | 69.2 (20.4) | 4.29**
| 0.20 | 65.3 (21.6) | 0.22 | 0.07 | 67.2 (21.3) | 2.16 | 0.10 |
RFr | 62.2 (25.0) | 59.3 (24.6) | −2.72 | −0.11 | 60.3 (24.0) | −1.33 | −0.05 | 64.4 (23.4) | 1.55 | 0.06 | 60.3 (23.6) | −1.67 | −0.07 |
RFa | 74.6 (22.5) | 73.2 (21.9) | −1.35 | −0.06 | 69.7 (25.3) | −4.46 |
−0.20
| 73.4 (23.0) | −1.83 | −0.08 | 72.6 (23.2) | −2.17 | −0.10 |
SSL | 63.3 (29.4) | 59.5 (28.7) | −3.65 | −0.12 | 57.7 (29.3) | −4.89* | −0.16 | 54.3 (30.5) | −9.62***
|
−0.32
| 56.1 (30.6) | −6.38* |
−0.21
|
COP | 66.1 (27.0) | 66.7 (26.1) | 0.36 | 0.01 | 67.2 (26.1) | 0.12 | 0.00 | 67.3 (27.2) | 1.14 | 0.04 | 64.5 (28.6) | −0.73 | −0.03 |
REJ | 78.7 (27.7) | 78.1 (24.4) | −0.36 | −0.01 | 79.4 (23.8) | 0.61 | 0.02 | 78.1 (24.8) | −0.38 | −0.01 | 78.2 (24.8) | −0.12 | −0.00 |
RHCS | 86.8 (14.8) | 82.6 (19.1) | −4.49**
|
−0.30
| 82.9 (17.2) | −3.96**
|
−0.
27
| 81.9 (20.4) | −4.93**
|
−0.
33
| 80.7 (19.7) | −5.98***
|
−0
.40
|
Index | 67.0 (13.1) | 65.8 (13.9) | −1.12 | −0.09 | 66.1 (13.1) | −1.08 | −0.08 | 65.7 (13.8) | −2.46**
| −0.19 | 65.2 (15.0) | −2.26 | −0.17 |
SF-36v2
|
M (SD)
|
M (SD)
|
D
M6-BL
|
ES
|
M (SD)
|
D
M12-BL
|
ES
|
M (SD)
|
D
M18-BL
|
ES
|
M (SD)
|
D
M24-BL
|
ES
|
PF | 48.4 (28.5) | 45.2 (29.0) | −2.95 | −0.10 | 46.6 (29.8) | −2.19 | −0.08 | 42.9 (30.4) | −5.37**
| −0.19 | 41.1 (32.0) | −7.84***
|
−0.
28
|
RP | 50.4 (27.9) | 50.3 (28.8) | −0.04 | −0.00 | 50.9 (28.1) | −0.55 | −0.02 | 45.1 (27.8) | −4.60 | −0.17 | 46.0 (29.8) | −4.83*
| −0.17 |
BP | 67.6 (26.3) | 64.1 (26.7) | −3.88 | −0.15 | 64.1 (25.7) | −3.10 | −0.12 | 61.6 (28.2) | −5.88**
|
−0.
22
| 60.9 (27.3) | −7.44***
|
−0.
28
|
GH | 49.5 (21.2) | 50.2 (18.8) | 0.89 | 0.04 | 47.4 (20.1) | −2.83 | −0.13 | 49.3 (20.0) | −0.59 | −0.03 | 47.9 (21.4) | −2.27 | −0.11 |
Vi | 43.5 (18.3) | 45.7 (20.2) | 2.08 | 0.11 | 44.6 (19.6) | 1.04 | 0.06 | 43.1 (19.4) | −0.58 | −0.03 | 44.1 (20.3) | 0.58 | 0.03 |
SF | 65.8 (24.1) | 64.9 (25.5) | −1.09 | −0.04 | 65.3 (27.4) | −0.25 | −0.01 | 65.0 (25.5) | −0.98 | −0.04 | 61.9 (28.7) | −3.85 | −0.16 |
RE | 53.0 (14.9) | 54.8 (12.5) | 1.29 | −0.09 | 52.5 (13.3) | −0.59 | −0.04 | 52.8 (13.7) | −0.80 | −0.05 | 51.7 (14.4) | −1.94 | −0.13 |
MH | 65.4 (18.7) | 66.8 (18.0) | 0.98 | 0.05 | 64.6 (20.5) | −1.04 | −0.06 | 64.3 (18.2) | −1.85 | −0.10 | 63.2 (20.4) | −3.12 | −0.17 |
PCS | 39.6 (9.9) | 38.1 (9.8) | −1.19 | −0.12 | 38.9 (9.5) | −0.93 | −0.09 | 37.4 (10.6) | −2.13**
|
−0.
22
| 37.3 (11.1) | −2.59***
|
−0.
26
|
MCS | 44.9 (8.6) | 46.2 (8.5) | 1.30 | 0.15 | 45.1 (8.6) | 0.50 | 0.06 | 45.1 (8.1) | 0.16 | 0.02 | 45.1 (8.9) | −0.11 | −0.01 |
Baseline | Month 6 | Month 12 | Month 18 | Month 24 | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MusiQoL | M (SD) | M (SD) | D
M6-BL
| ES | p
W/NW
| M (SD) | D
M12-BL
| ES | p
W/NW
| M (SD) | D
M18-BL
| ES | p
W/NW
| M (SD) | D
M24-BL
| ES | p
W/NW
|
ADL | 62.8 (24.7) | 64.7 (25.7) | 1.97**
| 0.08 | 0.065 | 65.2 (24.6) | 2.61***
| 0.11 | 0.109 | 65.0 (26.1) | 2.09***
| 0.08 |
0.035
| 63.4 (26.4) | 0.91 | 0.04 |
0.017
|
PWB | 62.3 (23.8) | 63.7 (24.7) | 1.63 | 0.07 | 0.187 | 65.8 (23.7) | 3.63***
| 0.15 | 0.410 | 65.6 (25.2) | 3.21***
| 0.13 |
0.029
| 66.9 (25.0) | 4.76***
|
0.20
| 0.145 |
SPT | 69.4 (22.3) | 70.2 (22.3) | 0.83 | 0.04 | 0.196 | 71.2 (21.0) | 1.58 | 0.07 | 0.140 | 71.1 (23.0) | 1.70 | 0.08 | 0.694 | 69.8 (23.2) | 1.45 | 0.01 | 0.441 |
RFr | 59.1 (29.0) | 58.1 (27.8) | −0.19 | −0.01 | 0.601 | 58.6 (28.5) | −0.19 | −0.01 | 0.937 | 58.1 (28.1) | −0.74 | −0.03 | 0.301 | 58.8 (27.9) | −0.20 | −0.01 | 0.754 |
RFa | 72.5 (27.7) | 71.5 (28.2) | −0.33 | −0.01 | 0.136 | 69.9 (28.6) | −2.26 | −0.08 | 0.362 | 69.6 (28.8) | −2.97*
| −0.11 | 0.792 | 70.0 (29.7) | −2.29 | −0.08 | 0.803 |
SSL | 63.6 (29.7) | 62.9 (29.9) | −0.39 | −0.01 | 0.383 | 62.4 (30.7) | −1.12 | −0.04 | 0.237 | 62.4 (30.3) | −1.91 | −0.06 |
0.010
| 63.2 (30.6) | −0.03 | −0.00 |
0.043
|
COP | 62.1 (29.6) | 64.8 (28.7) | 3.12**
| 0.10 | 0.149 | 65.3 (29.1) | 3.49**
| 0.12 | 0.370 | 65.6 (28.7) | 3.65**
| 0.12 | 0.879 | 65.5 (28.2) | 3.20*
| 0.11 | 0.467 |
REJ | 82.6 (23.9) | 84.2 (23.5) | 1.88*
| 0.08 | 0.242 | 84.2 (22.8) | 1.68 | 0.07 | 0.172 | 81.9 (24.4) | −0.76 | −0.03 | 0.749 | 82.3 (23.4) | −0.22 | −0.01 | 0.715 |
RHCS | 85.2 (19.4) | 84.7 (19.9) | −0.60 | −0.03 | 0.138 | 83.5 (20.6) | −1.71 | −0.09 | 0.517 | 83.5 (19.6) | −2.13*
| −0.11 | 0.603 | 83.0 (18.8) | −2.18*
| −0.11 | 0.219 |
Index | 68.5 (14.8) | 69.3 (15.0) | 0.90 | 0.06 | 0.160 | 69.4 (15.4) | 0.75 | 0.05 | 0.365 | 69.1 (16.4) | 0.27 | 0.02 |
0.014
| 69.4 (15.6) | 0.34 | 0.02 | 0.068 |
SF-36v2
|
M (SD)
|
M (SD)
|
D
M6-BL
|
ES
|
p
W/NW
|
M (SD)
|
D
M12-BL
|
ES
|
p
W/NW
|
M (SD)
|
D
M18-BL
|
ES
|
p
W/NW
|
M (SD)
|
D
M24-BL
|
ES
|
p
W/NW
|
PF | 65.2 (27.7) | 65.5 (27.4) | 0.11 | 0.00 | 0.472 | 65.9 (28.0) | 0.83 | 0.03 | 0.086 | 66.8 (29.0) | 1.11 | 0.04 | <10-3
| 65.4 (29.5) | 0.30 | 0.01 | <10-3
|
RP | 60.2 (29.6) | 62.0 (28.5) | 1.63 | 0.06 | 0.733 | 63.1 (28.7) | 3.08*
| 0.10 | 0.233 | 63.2 (28.8) | 2.77*
| 0.09 |
0.016
| 63.1 (28.6) | 3.06*
| 0.10 |
0.001
|
BP | 66.8 (27.2) | 66.9 (27.6) | 0.08 | 0.00 | 0.628 | 67.5 (25.5) | 0.36 | 0.01 | 0.866 | 68.2 (26.7) | 1.12 | 0.04 | 0.139 | 67.0 (26.5) | 0.28 | 0.01 |
0.044
|
GH | 54.7 (22.4) | 54.6 (22.4) | −0.02 | −0.01 | 0.766 | 54.9 (22.0) | 0.10 | 0.00 | 0.107 | 53.1 (23.0) | −1.35 | −0.06 | 0.646 | 52.7 (23.7) | −2.03*
| −0.09 | 0.859 |
Vi | 48.8 (22.3) | 49.3 (23.0) | 0.72 | 0.03 | 0.667 | 50.0 (22.4) | 1.22 | 0.05 | 0.779 | 50.4 (22.8) | 1.54 | 0.07 | 0.681 | 48.7 (23.2) | 0.09 | 0.00 | 0.965 |
SF | 69.0 (26.6) | 71.0 (27.0) | 2.12 | 0.08 | 0.330 | 70.4 (27.2) | 1.29 | 0.05 | 0.531 | 70.6 (26.2) | 1.71 | 0.06 | 0.356 | 70.3 (26.3) | 1.33 | 0.05 | 0.117 |
RE | 56.1 (13.7) | 56.0 (12.7) | −0.08 | −0.00 | 0.392 | 56.5 (12.0) | 0.27 | 0.02 | 0.251 | 56.2 (11.5) | −0.06 | −0.00 | 0.466 | 56.2 (12.3) | 0.04 | 0.00 | 0.124 |
MH | 63.9 (20.5) | 64.4 (21.3) | 0.65 | 0.03 | 0.853 | 65.3 (19.5) | 1.25 | 0.06 | 0.383 | 64.2 (20.6) | 0.29 | 0.01 | 0.132 | 64.4 (20.7) | 0.41 | 0.02 | 0.069 |
PCS | 44.1 (10.0) | 44.2 (10.1) | 0.11 | 0.01 | 0.702 | 44.4 (10.1) | 0.41 | 0.04 | 0.349 | 44.6 (10.5) | 0.54 | 0.05 |
0.003
| 44.1 (10.5) | 0.05 | 0.01 | <10-3
|
MCS | 43.8 (8.9) | 44.2 (9.0) | 0.38 | 0.04 | 0.260 | 44.3 (8.8) | 0.48 | 0.05 | 0.773 | 44.0 (9.0) | 0.04 | 0.00 | 0.973 | 44.0 (9.2) | 0.20 | 0.02 | 0.700 |