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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/219638
Biomarkers of Response to Ocrelizumab in Relapsing-Remitting Multiple Sclerosis
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Objective: To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing-remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response. Methods: Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity.
Results: After a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients. Conclusion: Ocrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA.
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QUIROGA VARELA, Ana, RODRÍGUEZ-JORGE, Fernando, FERNÁNDEZ-VELASCO, José ignacio, VILLARRUBIA, Noelia, GRACIA-GIL, Julia, FERNÁNDEZ, Eva, MECA LALLANA, Virginia, DÍAZ-PÉREZ, Carolina, SAINZ DE LA MAZA, Susana, PACHECO, Eva maria, RAMIÓ-TORRENTÀ, Lluis, MARTÍNEZ YÉLAMOS, Sergio, BAU VILA, Laura, MONREAL LAGUILLO, Enric, LOPEZ-REAL, Ana, RODERO-ROMERO, Alexander, BORREGA CANELO, Laura, DÍAZ, Santiago, EGUIA DEL RÍO, Pablo, ESPIÑO MARTÍNEZ, María mercedes, CHICO GARCÍA, Juan luis, BARRERO HERNÁNDEZ, Francisco javier, MARTÍNEZ-GINÉS, Maria luisa, GARCÍA-DOMÍNGUEZ, José manuel, DE LA FUENTE, Soraya, MORENO TORRES, Irene, SAINZ-AMO, Raquel, MAÑÉ MARTÍNEZ, M. alba, CAMINERO RODRÍGUEZ, Ana belén, CASTELLANOS PINEDO, Fernando, GÓMEZ LÓPEZ, Ana, LABIANO-FONTCUBERTA, Andres, AYUSO PERALTA, Lucía, ABREU, Rossana, HERNÁNDEZ PÉREZ, Miguel ángel, MECA LALLANA, José e., MARTÍN-AGUILAR, Lorena, MURIEL GARCÍA, Alfonso, MASJUAN VALLEJO, Jaime, COSTA FROSSARD, Lucienne, VILLAR, Luisa m.. Biomarkers of Response to Ocrelizumab in Relapsing-Remitting Multiple Sclerosis. _Frontiers in Immunology_. 2024. Vol. 15. [consulta: 20 de gener de 2026]. ISSN: 1664-3224. [Disponible a: https://hdl.handle.net/2445/219638]