Table 3:
Annualized Cervical Cord Atrophy Rates of Patient Subsets before Conversion/Silent Progression
| Patient Subset | RR→RR | RR→SP | Diff (95% CI) | p |
|---|---|---|---|---|
| RR→RR/RR→SP | ||||
| Subset without C1 Lesions (n=60) | −1.04 | −2.28 | −1.24 (−1.77; −0.70) | <0001 |
| By Time Interval Before Conversion | ||||
| 0 y (334 Visits) | −0.89 | −2.14 | −1.25 (−1.80; −0.70) | <0.001 |
| −1 y (304 Visits) | −0.85 | −2.18 | −1.33 (−2.00; −0.67) | <0.001 |
| −2 y (281 Visits) | −0.73 | −2.21 | −1.48 (−2.23; −0.72) | <0.001 |
| −3 y (253 Visits) | −0.72 | −2.17 | −1.45 (2.40; −0.49) | 0.004 |
| −4 y (219 Visits) | −0.73 | −2.23 | −1.50 (−2.69; −0.32) | 0.015 |
| Relative to Conversion | Before | After | Diff (95% CI) | p |
| RR→SP group | −2.24 | −1.63 | 0.61 (0.16; 1.05) | 0.010 |
| Minimum Observational Time Needed to Detect Difference in Atrophy Rates | ||||
| Scans before conversion | RR→RR | RR→SP | Diff (95% CI) | p |
| 2 (419 visits) | −1.31 | −2.33 | −1.02 (−2.28; 0.25) | 0.103 |
| 3 (372 visits) | −1.14 | −2.29 | −1.15 (−1.92; −0.39) | 0.004 |
| 4 (301 visits) | −1.20 | −2.30 | −1.10 (−1.69; −0.51) | <0.001 |
| 5 (216 visits) | −1.11 | −2.36 | −1.25 (−1.75; −0.75) | <0.001 |
| Silent Progression Groups as defined in Cree et al.1 | ||||
| Worsening | Atrophy Rate† | vs.* | Diff (95% CI) | p |
| Non-relapsing (W/NR) | −1.10 | NW/NR | 0.38 (0.15; 0.60) | 0.004 |
| Relapsing (W/R) | −0.89 | W/NR | −0.21 (−0.46; 0.02) | 0.112 |
| Stable | ||||
| Non-relapsing (NW/NR) | −0.72 | W/R | −0.17 (−0.38;0.05) | 0.137 |
| Relapsing (NW/R) | −0.80 | W/NR | −0.30 (−0.52; −0.07) | 0.020 |
Subsets: Subset without C1 lesions = subset of patients without focal white matter lesions at the C1A measurement level; by time interval before conversion (−4 to 0 years): patient subset with scans available for all intervals listed; relative to conversion: comparison of atrophy rate before and after conversion to SPMS; minimum observational time needed to detect difference in atrophy rates: minimum observational time, i.e., number of scans, to detect a meaningful difference in atrophy rate between RR→RR and RR→SP groups; of note, the difference between rates is detectable within 1 year of follow up and reaching statistical significance within 2 years of follow up; silent progression groups as defined by Cree et al.1 classifying RRMS and SPMS patients solely based on confirmed EDSS worsening (worsening/non-worsening), i.e., silent progression, and disease activity (relapsing/non-relapsing), thereby avoiding the dichotomy of the current RRMS/SPMS classification.
Control = healthy control. RR→RR = patients remaining relapsing remitting multiple sclerosis during the 12-year observation period. RR→SP = patients converting to secondary progressive multiple sclerosis during the 12-year observation period. NR = non-relapsing. NW = non-worsening, i.e., stable. R = relapsing. W = worsening. C1A = cervical cord area at C1 vertebral level. Diff (95% CI) = mean difference (lower and upper 95% confidence interval) between the respective patient groups. Atrophy rates are annual percentage change. P-values are corrected for multiple comparisons.
Between group comparison between the two groups mentioned in the respective row.
Comparisons not mentioned in the table: NW/NR vs. NW/R: −0.08 (95% CI: −0.28; 0.11), p=0.416; NW/R vs. W/R: −0.09 (95% CI: −0.30; 0.13), p=0.448. C1A rates were calculated based on mixed-effects models, adjusted for age, sex and disease duration.