Table 2.
Univariable and multivariable cox proportional hazard regression models for intrathecal biomarkers measured at diagnosis as well as covariates and prediction of EDA-3 and PIRA
| EDA-3 | PIRA | |||||
|---|---|---|---|---|---|---|
| HR | 95%CI | p-value | HR | 95%CI | p-value | |
| Univariable | ||||||
| KFLC indexa | 1.001 | 1.00006–1.003 | 0.041 | 1.003 | 1.001–1.006 | 0.003 |
| KFLC index > 100b | 1.99 | 1.19–3.34 | 0.008 | 4.6 | 1.5–14.07 | 0.007 |
| CSF KFLCa | 1.046 | 1.012–1.081 | 0.008 | 1.087 | 1.027–1.15 | 0.004 |
| CSF Taua | 1.001 | 0.99–1.003 | 0.387 | 1.002 | 0.99–1.005 | 0.224 |
| Disease duration | 0.99 | 0.98–1.002 | 0.172 | 1.002 | 0.99–1.010 | 0.642 |
| Total follw-up time | 1.007 | 0.99–1.016 | 0.17 | 1.002 | 0.99–1.01 | 0.64 |
| Time from sampling to DMT start | 1.001 | 1–1.002 | 0.037 | 0.99 | 0.98–1.002 | 0.14 |
| Age | 0.99 | 0.96–1.014 | 0.39 | 1.008 | 0.96–1.05 | 0.73 |
| Sex (ref. F) | 1.2 | 0.71– 2.05 | 0.48 | 1.51 | 0.58–3.9 | 0.39 |
| Disease course (ref. CIS) | 0.35 | 0.19–0.63 | < 0.001 | 2.98 | 0.39–22.47 | 0.29 |
| Onset EDSS | 0.98 | 0.79–1.21 | 0.82 | – | – | – |
| BL/RBL EDSS | – | – | – | 0.61 | 0.4–0.93 | 0.02 |
| BL T2W lesions (ref. < 10) | 0.94 | 0.567–1.551 | 0.802 | 2.4 | 0.85–6.7 | 0.099 |
| BL CEL | 1.11 | 0.67–1.84 | 0.67 | 0.7 | 0.27–1.75 | 0.43 |
| Exposure to he-DMT from onset | 0.54 | 0.32–0.91 | 0.02 | – | – | – |
| Treatment strategy | ||||||
| First-line | – | – | – | Ref | – | – |
| Escalation | – | – | – | 1.88 | 0.5–7.1 | 0.35 |
| he-DMT | – | – | – | 0.9 | 0.3–2.7 | 0.86 |
| Multivariable | ||||||
| KFLC indexa | 1.002 | 1.001–1.004 | 0.007 | 1.005 | 1.002–1.008 | 0.002 |
| KFLC index > 100b | 2.1 | 1.25–3.61 | 0.005 | 3.7 | 1.101–12.3 | 0.03 |
| CSF KFLCa | 1.053 | 1.016–1.09 | 0.005 | 1.08 | 1.006–1.16 | 0.033 |
| CSF Taua | 1.001 | 0.99–1.003 | 0.47 | 1.003 | 0.99–1.006 | 0.099 |
| Disease duration | 0.996 | 0.99–1.003 | 0.27 | 1.001 | 0.99–1.013 | 0.86 |
| Total follw-up time | 1.006 | 0.996–1.016 | 0.27 | 1.01 | 0.99–1.031 | 0.362 |
| Time from sampling to DMT start | 0.999 | 0.998–1.001 | 0.6 | 0.99 | 0.98–1.001 | 0.072 |
| Age | 0.99 | 0.97–1.027 | 0.882 | 1.002 | 0.95–1.06 | 0.94 |
| Sex (ref. F) | 1.61 | 0.9–2.87 | 0.1 | 3.24 | 1.001–10.49 | 0.05 |
| Disease course (ref. CIS) | 0.235 | 0.09–0.61 | 0.003 | 0.947 | 0.034–26.16 | 0.97 |
| Onset EDSS | 1.101 | 0.877–1.34 | 0.4 | – | – | – |
| BL/RBL EDSS | – | – | – | 0.624 | 0.344–1.13 | 0.12 |
| BL T2W lesions (ref. < 10) | 1.26 | 0.68–2.3 | 0.46 | 3.64 | 0.97–13.6 | 0.054 |
| BL CEL | 1.41 | 0.82–2.44 | 0.21 | 0.63 | 0.23–2.422 | 0.63 |
| Exposure to he-DMT from onset | 0.521 | 0.28–0.96 | 0.036 | – | – | – |
| Treatment strategy | ||||||
| First-line | – | – | – | Ref | – | – |
| Escalation | – | – | – | 4.48 | 0.66–30.25 | 0.124 |
| he-DMT | – | – | – | 0.6 | 0.16–2.24 | 0.45 |
Bold text indicates p values < 0.05
EDA evidence of disease activity, HR hazard ratio, CI confidence interval, CSF cerebrospinal fluid, KFLC kappa free light chain, Ig immunoglobulin, he high-efficacy, DMT disease modifying therapy, BL baseline, RBL re-baseline, EDSS expanded disability status scale, T2W T2-weighted, CEL contrast-enhancing lesion
aContinuous variable
bCategorical binary variable