AUTHOR=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 María , Quiroga Ana , Ramió-Torrentà Lluis , Martínez-Yélamos Sergio , Bau Laura , Monreal Enric , López-Real Ana , Rodero-Romero Alexander , Borrega Laura , Díaz Santiago , Eguía Pablo , Espiño Mercedes , Chico-García Juan Luis , Barrero Francisco Javier , Martínez-Ginés María Luisa , García-Domínguez José Manuel , De la Fuente Soraya , Moreno Irene , Sainz-Amo Raquel , Mañé-Martínez M. Alba , Caminero Ana , Castellanos-Pinedo Fernando , Gómez López Ana , Labiano-Fontcuberta Andrés , Ayuso Lucía , Abreu Rossana , Hernández Miguel Ángel , Meca-Lallana José , Martín-Aguilar Lorena , Muriel García Alfonso , Masjuan Jaime , Costa-Frossard Lucienne , Villar Luisa María 

TITLE=Biomarkers of response to ocrelizumab in relapsing–remitting multiple sclerosis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1480676

DOI=10.3389/fimmu.2024.1480676

ISSN=1664-3224

ABSTRACT=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 one-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in 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 on 12 months examination.
At baseline, INFL patients had higher sNfL (p=0.0003) and sGFAP (p=0.03) than 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 three months after ocrelizumab initiation indicated a higher risk of inflammation (OR=13.6; p<0.0001). Decrease of 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 PIRA group. Our data suggest that normalization of sNfL and sGFAP associate with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA.