Table 2. Multivariable Mixed Linear Models Investigating the Association of Worsening Status (Stable Multiple Sclerosis [MS] vs Worsening Progressive MS) With Log-Transformed Serum Glial Fibrillary Acidic Protein (sGFAP) and Serum Neurofilament Light Chain (sNfL) Levels.
| Model | Sample, No. | sGFAP, median (IQR), pg/mL | Estimate (95% CI)a | P value | sNfL, median (IQR), pg/mL | Estimate (95% CI) | P value |
|---|---|---|---|---|---|---|---|
| Model 1: simple | |||||||
| Follow-up time | NA | NA | 1.019 (1.011-1.026) | <.001 | NA | 1.017 (1.008-1.027) | <.001 |
| Progression | |||||||
| Stable MS | 169 | 63.2 (43.4-90.7) | NA | NA | 7.1 (5.4-9.4) | NA | NA |
| Worsening progressive MS | 184 | 103.0 (81.3-132.5) | 1.642 (1.226-2.199) | .002 | 10.9 (8.2-13.9) | 1.422 (1.104-1.831) | .01 |
| Model 2: multivariable | |||||||
| Age at baseline | NA | NA | 1.008 (0.993-1.023) | .35 | NA | 1.019 (1.009-1.029) | .002 |
| Follow-up time | NA | NA | 1.016 (1.007-1.025) | <.001 | NA | 1.019 (1.008-1.030) | .001 |
| Sex | |||||||
| Female | 224 | 87.7 (57.3-109.7) | 1.026 (0.764-1.378) | .87 | 8.4 (6.3-10.9) | 0.875 (0.725-1.058) | .21 |
| Male | 129 | 84.3 (57.7-121.1) | NA | 11.8 (5.8-16.7) | NA | ||
| BMIb | NA | NA | 0.991 (0.973-1.008) | .32 | NA | 0.969 (0.953-0.985) | <.001 |
| Disease duration at baseline | NA | NA | 1.002 (0.985-1.018) | .86 | NA | 1.005 (0.994-1.016) | .40 |
| DMT | |||||||
| Untreated | 48 | 97.4 (63.8-112.9) | NA | NA | 11.7 (8.7-16.4) | NA | NA |
| Platform | 40 | 68.6 (57.7-90.4) | 1.191 (1.048-1.356) | .009 | 9.7 (6.3-17.4) | 0.956 (0.821-1.142) | .59 |
| Orals | 118 | 74.7 (39.4-97.4) | 1.032 (0.933-1.139) | .54 | 7.7 (5.3-9.5) | 0.921 (0.811-1.039) | .20 |
| mAB | 147 | 103.6 (68.4-136.5) | 1.080 (0.997-1.171) | .06 | 9.4 (6.8-12.8) | 0.938 (0.842-1.035) | .22 |
| EDSS score | NA | NA | 1.011 (0.982-1.041) | .46 | NA | 1.002 (0.969-1.039) | .92 |
| Progression | |||||||
| Stable MS | 169 | 63.2 (43.4-90.7) | NA | NA | 7.1 (5.4-9.4) | NA | NA |
| Worsening progressive MS | 184 | 103.0 (81.3-132.5) | 1.575 (1.178-2.106 | .006 | 10.9 (8.2-13.9) | 1.248 (1.024-1.521) | .05 |
| Model 3: plus sNfL/sGFAP | |||||||
| Age at baseline | NA | NA | 1.004 (0.990-1.0.19) | .59 | NA | 1.016 (1.007-1.026) | .004 |
| Follow-up time | NA | NA | 1.012 (1.004-1.021) | .005 | NA | 1.014 (1.003-1.025) | .01 |
| Sex | |||||||
| Female | 224 | 87.7 (57.3-109.7) | 1.053 (0.792-1.400) | .74 | 8.4 (6.3-10.9) | 0.868 (0.725-1.040) | .17 |
| Male | 129 | 84.3 (57.7-121.1) | NA | NA | 11.8 (5.8-16.7) | NA | NA |
| BMIb | NA | NA | 0.996 (0.979-1.013) | .66 | NA | 0.973 (0.958-0.989) | .002 |
| Disease duration at baseline | NA | NA | 1.001 (0.985-1.017) | .94 | NA | 1.005 (0.994-1.1015) | .42 |
| DMT | |||||||
| Untreated | 48 | 97.4 (63.8-112.9) | NA | NA | 11.7 (8.7-16.4) | NA | NA |
| Platform | 40 | 68.6 (57.7-90.4) | 1.214 (1.072-1.377) | .003 | 9.7 (6.3-17.4) | 0.907 (0.782-1.082) | .24 |
| Oral | 118 | 74.7 (39.4-97.4) | 1.045 (0.948-1.151) | .37 | 7.7 (5.3-9.5) | 0.917 (0.812-1.032) | .17 |
| mAB | 147 | 103.6 (68.4-136.5) | 1.090 (1.008-1.179) | .03 | 9.4 (6.8-12.8) | 0.918 (0.827-1.010) | .10 |
| EDSS score | NA | NA | 1.012 (0.984-1.041) | .41 | NA | 0.999 (0.968-1.036) | .98 |
| sNfL per doubling, pg/mL | NA | NA | 1.141 (1.079-1.207) | <.001 | NA | NA | NA |
| sGFAP per doubling, pg/mL | NA | NA | NA | NA | NA | 1.217 (1.120-1.315) | <.001 |
| Progression | |||||||
| Stable MS | 169 | 63.2 (43.4-90.7) | NA | NA | 7.1 (5.4-9.4) | NA | NA |
| Worsening progressive MS | 184 | 103.0 (81.3-132.5) | 1.509 (1.139-1.998) | .01 | 10.9 (8.2-13.9) | 1.099 (0.905-1.339) | .38 |
Abbreviations: BMI, body mass index; DMT, disease modifying treatment; EDSS, Expanded Disability Status Scale; mAB, monoclonal antibody therapies; NA, not applicable; sGFAP, serum glial fibrillary acidic protein; sNfL, serum neurofilament light chain.
a
Estimates are back transformed and represent multiplicative effects.
b
Calculated as weight in kilograms divided by height in meters squared.