Table 2.
Group statistics for predicted responders and non-responders to anti-CD20-Abs at the 50th and 70th percentile thresholds, in the held-out test set
| 50th percentile thresholda | 70th percentile thresholda | |||||||
|---|---|---|---|---|---|---|---|---|
| Responders | Non-responders | Effect size (95% CI)b | p valuec | Responders | Non-responders | Effect size (95% CI)b | p valuec | |
| Trial contribution | ||||||||
| OLYMPUS | 55 | 54 | 35 | 74 | ||||
| ORATORIO | 96 | 92 | 57 | 131 | ||||
| Demographics | ||||||||
| Age (years) | 45.20 (8.58) | 47.84 (7.89) | −2.64 (-4.53, −0.76) | 0.006 | 44.59 (9.05) | 47.36 (7.87) | −2.77 (−4.93, −0.61) | 0.013 |
| Sex (% male) | 47.02 | 50.68 | 0.86 (0.53, 1.40) | 0.562 | 45.65 | 50.24 | 0.83 (0.49, 1.40) | 0.530 |
| Height (cm) | 170.05 (10.56) | 170.55 (8.80) | −0.50 (−2.72, 1.71) | 0.657 | 169.78 (10.29) | 170.52 (9.47) | −0.74 (−3.23, 1.75) | 0.560 |
| Weight (kg) | 76.17 (18.93) | 72.96 (13.77) | 3.21 (−0.56, 6.98) | 0.096 | 75.68 (20.07) | 74.10 (14.87) | 1.58 (−3.04, 6.20) | 0.502 |
| Disease duration (years) | 6.07 (4.14) | 8.72 (5.45) | −2.65 (−3.76, −1.54) | <0.001 | 5.79 (4.15) | 8.09 (5.19) | −2.30 (−3.41, −1.19) | <0.001 |
| Disability scores | ||||||||
| EDSS | 4.87 (1.18) | 4.52 (1.23) | 0.34 (0.07, 0.62) | 0.015 | 5.07 (1.14) | 4.53 (1.21) | 0.54 (0.25, 0.83) | <0.001 |
| FSS-Bowel and Bladder | 1.25 (0.93) | 1.11 (0.80) | 0.14 (−0.05, 0.34) | 0.157 | 1.27 (0.98) | 1.15 (0.82) | 0.12 (−0.11, 0.35) | 0.315 |
| FSS-Brainstem | 0.82 (0.93) | 0.79 (0.87) | 0.04 (−0.17, 0.24) | 0.726 | 0.90 (0.95) | 0.77 (0.88) | 0.13 (−0.10, 0.36) | 0.265 |
| FSS-Cerebellar | 2.38 (0.97) | 1.78 (1.05) | 0.60 (0.37, 0.83) | <0.001 | 2.57 (0.81) | 1.86 (1.08) | 0.71 (0.48, 0.93) | <0.001 |
| FSS-Cerebral | 1.07 (0.83) | 1.05 (0.89) | 0.02 (−0.18, 0.22) | 0.848 | 1.13 (0.84) | 1.04 (0.87) | 0.09 (−0.12, 0.30) | 0.404 |
| FSS-Pyramidal | 2.75 (0.69) | 2.90 (0.58) | −0.14 (−0.29, 0.00) | 0.052 | 2.77 (0.76) | 2.85 (0.58) | −0.08 (−0.26, 0.10) | 0.382 |
| FSS-Sensory | 1.55 (1.06) | 1.64 (1.02) | −0.08 (−0.32, 0.15) | 0.488 | 1.56 (1.00) | 1.61 (1.06) | −0.05 (−0.30, 0.20) | 0.703 |
| FSS-Visual | 1.04 (1.04) | 0.43 (0.62) | 0.62 (0.42, 0.81) | <0.001 | 1.28 (1.07) | 0.50 (0.71) | 0.78 (0.54, 1.02) | <0.001 |
| Mean T25FW (s) | 13.55 (17.61) | 10.75 (11.08) | 2.80 (−0.55, 6.15) | 0.103 | 15.95 (21.79) | 10.48 (9.82) | 5.47 (0.77, 10.17) | 0.024 |
| Mean 9HPT dominant (s) | 32.62 (26.89) | 26.70 (10.24) | 5.92 (1.29, 10.55) | 0.013 | 36.01 (33.25) | 26.88 (9.89) | 9.13 (2.12, 16.15) | 0.012 |
| Mean 9HPT non-dominant (s) | 37.33 (31.11) | 26.97 (9.32) | 10.36 (5.14, 15.58) | <0.001 | 42.39 (38.33) | 27.68 (9.33) | 14.71 (6.68, 22.75) | <0.001 |
| MRI metrics | ||||||||
| Gad count | 1.62 (3.14) | 0.16 (0.48) | 1.46 (0.95, 1.97) | <0.001 | 1.90 (3.64) | 0.46 (1.27) | 1.44 (0.67, 2.22) | <0.001 |
| T2 lesion volume (mL) | 13.09 (12.85) | 7.72 (10.17) | 5.37 (2.73, 8.01) | <0.001 | 14.31 (14.22) | 8.72 (10.27) | 5.59 (2.33, 8.85) | <0.001 |
| Normalized brain volume (L) | 1.37 (0.16) | 1.38 (0.16) | −0.02 (−0.05, 0.02) | 0.367 | 1.35 (0.16) | 1.38 (0.16) | −0.03 (−0.07, 0.01) | 0.107 |
Values in brackets are standard deviations, unless otherwise specified.
EDSS Expanded Disability Status Scale, FSS Functional Systems Score, T25FW timed 25-foot walk, 9HPT 9-hole peg test, Gad Gadolinium-enhancing lesion.
a Percentile threshold for defining responders. The 50th percentile defines responders as the top 50% who are predicted to be most responsive, while the 70th percentile defines them as the top 30%. The non-responders are those who fall below the percentile threshold.
b Effect size is the average difference between responders and non-responders for all covariates except for "sex” which is an odd’s ratio (OR).
c p values for continuous and ordinal variables are calculated using a two-sided Welch’s t test due to unequal variances/sample sizes. p value for the categorical variable "sex” is calculated using a two-sided Fisher’s exact test due to unequal and relatively small sample sizes. Exact p-values for the 50th percentile threshold: disease duration, p = 4.39 × 10−6; FSS-Cerebellar, p = 6.42 × 10−7; FSS-Visual, p = 2.18 × 10−9; Mean 9HPT non-dominant, p = 1.36 × 10−4; Gad count, p = 8.72 × 10−8; T2 lesion volume, p = 8.57 × 10−5. Exact p-values for the 70th percentile threshold: disease duration, p = 7.04 × 10−5; EDSS, p = 3.03 × 10−4; FSS-Cerebellar, p = 2.61 × 10−9; FSS-Visual, p = 3.38 × 10−9; Mean 9HPT non-dominant, p = 4.82 × 10−4; Gad count, p = 3.69 × 10−4; T2 lesion volume, p = 9.59 × 10−4.