Serum Glial Fibrillary Acidic Protein Dynamics, Disease Progression, and Therapy Response in Multiple Sclerosis.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Einsiedler Maximilian, Sandgren Sofia, Schaedelin Sabine, Ning Kiarra, Maleska Maceski Aleksandra, Oechtering Johanna, Cordano Christian, Melie-Garcia Lester, Gelfand Jeffrey M, Cagol Alessandro, Henry Roland G, Finkener Sebastian, Lalive Patrice H, Müller Stefanie, Pot Caroline, Mathias Amandine, Du Pasquier Renaud, Hoepner Robert, Chan Andrew, Disanto Giulio, Zecca Chiara, D'Souza Marcus, Hemkens Lars G, Yaldizli Özgür, Fischer-Barnicol Bettina, Derfuss Tobias, Roth Patrick, Herwerth Marina, Gobbi Claudio, Brassat David, Tackenberg Björn, Pedotti Rosetta, Wiendl Heinz, Berger Klaus, Hermesdorf Marco, Arrambide Georgina, Piehl Fredrik, Zetterberg Henrik, Cree Bruce A C, Sormani Maria Pia, Kappos Ludwig, Hauser Stephen L, Khalil Michael, Granziera Cristina, Green Ari J, Leppert David, Benkert Pascal, Abdelhak Ahmed, Kuhle Jens, Expression, Proteomics, Imaging, Clinical (EPIC) study and the Swiss MS Cohort (SMSC) investigators, Hofer Lisa, Hughes Michelle, Genc Nafiye, Zadic Amar, Vilchez Gomez Juan Francisco, Galbusera Riccardo, Galli Edoardo, Müller Jannis, Uginet Marjolaine, Kana Veronika, Raposo Catarina, Oksenberg Jorge, Conen David
Аннотация
OBJECTIVE: To investigate whether serum GFAP levels and treatment-related changes are associated with future progression independent of relapse activity (PIRA).
DESIGN, SETTING, AND PARTICIPANTS: This was a prospective observational study using 2 large MS cohorts: the Swiss MS Cohort (SMSC; initiated in June 2012; data extraction September 22, 2025) and the Expression, Proteomics, Imaging, Clinical study (EPIC; initiated in July 2004; data extraction February 21, 2024). The study took place at tertiary MS centers (8 for SMSC and 1 for EPIC). A total of 2329 persons with MS from both cohorts with at least 1 available time point with neurofilament light chain (NfL) and GFAP measurements were included (overall 18 629 measurements).
EXPOSURES: Clinical data and NfL and GFAP z scores, collected and calculated every 6 or 12 months.
MAIN OUTCOMES AND MEASURES: Risk of future PIRA, defined as Expanded Disability Status Scale score worsening confirmed after 6 or more months without relapses (in SMSC), or a composite additionally including greater than 20% worsening in the 9-hole peg test or timed 25-ft walk test (in EPIC).
RESULTS: The SMSC and EPIC cohorts consisted of 1709 (13 375 samples; median [IQR] follow-up, 6.9 [2.5-10.7] years and age, 40.6 [32.1-50.1] years; 1128 [66.0%] female) and 620 (5254 samples; median [IQR] follow-up, 13.1 [9.4-14.0] years and age, 42.0 [35.0-50.0] years; 432 [69.7%] female) persons with MS, respectively. Consistent with prior work, high NfL was associated with relapse risk within the next year, whereas high GFAP was associated with long-term PIRA risk. In addition, elevated GFAP (z score >1.0 [84th percentile]) was associated with an average 40% higher hazard of short-term PIRA in the subsequent visit interval (SMSC: median [IQR] 346 [190-375] days; hazard ratio [HR], 1.45, 95% CI, 1.21-1.75; P < .001; EPIC: 385 [355-518] days; HR, 1.36; 95% CI, 1.07-1.71; P = .01). GFAP-based cohort enrichment in clinical trials targeting PIRA as an end point could reduce sample size by approximately 20%. Further, in SMSC, every yearly GFAP z score unit reduction during the first 2 years receiving fingolimod or B-cell-depleting therapy was associated with a lower risk of subsequent PIRA (54% risk reduction; HR, 0.46; 95% CI, 0.26-0.84; P = .01 and 67% risk reduction; HR, 0.33; 95% CI, 0.18-0.61; P < .001), respectively.
CONCLUSIONS AND RELEVANCE: In this cohort study, elevated GFAP was associated with a higher risk of PIRA, while treatment-associated reductions were associated with a lower PIRA risk. Together, these results suggest that serum GFAP may serve as a biomarker for personalized risk stratification and treatment monitoring and as a screening tool to reduce cohort size in clinical trials targeting MS progression.