TY - JOUR
T1 - Glial fibrillary acidic protein and multiple sclerosis progression independent of acute inflammation
AU - Jiang, Xiaotong
AU - Shen, Changyu
AU - Teunissen, Charlotte E.
AU - Wessels, Mark
AU - Zetterberg, Henrik
AU - Giovannoni, Gavin
AU - Singh, Carol M.
AU - Caba, Bastien
AU - Elliott, Colm
AU - Fisher, Elizabeth
AU - de Moor, Carl
AU - Belachew, Shibeshih
AU - Gafson, Arie R.
N1 - Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by Biogen (Cambridge, MA, USA). The authors had full editorial control of the manuscript and provided their final approval of all content. Publisher Copyright: © The Author(s), 2023.
PY - 2023/8
Y1 - 2023/8
N2 - Background: The clinical relevance of serum glial fibrillary acidic protein (sGFAP) concentration as a biomarker of MS disability progression independent of acute inflammation has yet to be quantified. Objective: To test whether baseline values and longitudinal changes in sGFAP concentration are associated with disability progression without detectable relapse of magnetic resonance imaging (MRI) inflammatory activity in participants with secondary-progressive multiple sclerosis (SPMS). Methods: We retrospectively analyzed longitudinal sGFAP concentration and clinical outcome data from the Phase 3 ASCEND trial of participants with SPMS, with no detectable relapse or MRI signs of inflammatory activity at baseline nor during the study (n = 264). Serum neurofilament (sNfL), sGFAP, T2 lesion volume, Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and composite confirmed disability progression (CDP) were measured. Linear and logistic regressions and generalized estimating equations were used in the prognostic and dynamic analyses. Results: We found a significant cross-sectional association between baseline sGFAP and sNfL concentrations and T2 lesion volume. No or weak correlations between sGFAP concentration and changes in EDSS, T25FW, and 9HPT, or CDP were observed. Conclusion: Without inflammatory activity, changes in sGFAP concentration in participants with SPMS were neither associated with current nor predictive of future disability progression.
AB - Background: The clinical relevance of serum glial fibrillary acidic protein (sGFAP) concentration as a biomarker of MS disability progression independent of acute inflammation has yet to be quantified. Objective: To test whether baseline values and longitudinal changes in sGFAP concentration are associated with disability progression without detectable relapse of magnetic resonance imaging (MRI) inflammatory activity in participants with secondary-progressive multiple sclerosis (SPMS). Methods: We retrospectively analyzed longitudinal sGFAP concentration and clinical outcome data from the Phase 3 ASCEND trial of participants with SPMS, with no detectable relapse or MRI signs of inflammatory activity at baseline nor during the study (n = 264). Serum neurofilament (sNfL), sGFAP, T2 lesion volume, Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and composite confirmed disability progression (CDP) were measured. Linear and logistic regressions and generalized estimating equations were used in the prognostic and dynamic analyses. Results: We found a significant cross-sectional association between baseline sGFAP and sNfL concentrations and T2 lesion volume. No or weak correlations between sGFAP concentration and changes in EDSS, T25FW, and 9HPT, or CDP were observed. Conclusion: Without inflammatory activity, changes in sGFAP concentration in participants with SPMS were neither associated with current nor predictive of future disability progression.
KW - Multiple sclerosis
KW - biomarker
KW - disability progression
KW - glial fibrillary acidic protein
KW - neurofilament light chain
KW - non-inflammatory
UR - http://www.scopus.com/inward/record.url?scp=85162646875&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/13524585231176732
DO - https://doi.org/10.1177/13524585231176732
M3 - Article
C2 - 37317870
SN - 1352-4585
VL - 29
SP - 1070
EP - 1079
JO - MULTIPLE SCLEROSIS JOURNAL
JF - MULTIPLE SCLEROSIS JOURNAL
IS - 9
ER -