Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis.
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Abdelhak Ahmed, Bachhuber Franziska, Ning Kiarra, Benkert Pascal, John Boscardin W, Maleska Maceski Aleksandra, Schaedelin Sabine, Achtnichts Lutz, Finkener Sebastian, Lalive Patrice H, Uginet Marjolaine, Pot Caroline, Du Pasquier Renaud, Hoepner Robert, Chan Andrew, Gobbi Claudio, Zecca Chiara, Müller Stefanie, Roth Patrick, Granziera Cristina, Chitnis Tanuja, Madill Evan, Weiner Howard L, Green Ari J, Hauser Stephen L, Cree Bruce Ac, Kümpfel Tania, Havla Joachim, Skripuletz Thomas, Gingele Stefan, Senel Makbule, Vardakas Ioannis, Taranu Daniela, Ziemann Ulf, Kowarik Markus C, Kleiter Ingo, Hoshi Muna-Miriam, Zettl Uwe K, Haarmann Axel, Thebault Simon, Freedman Mark S, Bergman Hailey P, Iacobaeus Ellen, Khademi Mohsen, Ferraro Diana, Cardi Martina, Mariotto Sara, Comabella Manuel, Montalban Xavier, Vilaseca Andreu, Strijbis Eva M, Wessels Mark Hj, Killestein Joep, Hemmer Bernhard, Held Friederike, Sellebjerg Finn, Højsgaard Chow Helene, Alvarez-Lafuente Roberto, Domínguez-Mozo Maria Inmaculada, Hegen Harald, Berek Klaus, Deisenhammer Florian, Thouvenot Eric, Agherbi Hanane, Rejdak Konrad, Gąsior Magda, Tzanetakos Dimitrios, Tzartos John S, Sormani Maria Pia, Dujmovic Basuroski Irena, Arrambide Georgina, Khalil Michael, Piehl Fredrik, Teunissen Charlotte E, Kuhle Jens, Tumani Hayrettin
Аннотация
METHODS: Data were collected from BioMS-eu network centres and collaborating cohorts. pwPMS with primary progressive MS (PPMS) or secondary progressive MS (SPMS) with at least one GFAP value and at least three follow-up expanded disability status scale (EDSS) scores were included. The prognostic value of serum GFAP and NfL age- and sex-adjusted Z-scores for future CDW was evaluated using Cox regression models, accounting for sex, age, baseline disease duration and EDSS, and dominant treatment during follow-up.
RESULTS: 1058 participants and 7530 encounters were included (median age 53 years (IQR: 44 to 59), 57% female, follow-up 4.6 years (2.9 to 8.4)) with median baseline GFAP of 0.74 (-0.10 to 1.55) and NfL of 0.64 (-0.36 to 1.51). 723 CDW events were recorded. Each GFAP Z-score increase was associated with ~10% higher CDW risk (adjusted HR (aHR) 1.107 (1.001 to 1.225), p=0.049). Results were mainly driven by SPMS participants (n=613, aHR 1.242 (1.073 to 1.438), p=0.004). Higher NfL Z-scores predicted CDW only in PPMS participants (1.236 (1.092 to 1.399), p=0.001).
CONCLUSIONS: GFAP was a prognostic indicator for future CDW in pwPMS, especially in pwSPMS. On the other hand, NfL was predictive of CDW only in pwPPMS.